Axial psoriatic arthritis: An update for dermatologists

Open AccessPublished:July 31, 2020DOI:https://doi.org/10.1016/j.jaad.2020.05.089
      Psoriasis is a chronic, immune-mediated, systemic, inflammatory disorder characterized by skin plaques and, often, nail disease and arthritis that contribute to reduced quality of life. Psoriatic arthritis—a heterogeneous, inflammatory, musculoskeletal disease that can cause permanent damage to both peripheral and axial joints—is the most common comorbidity of psoriasis. Axial disease occurs in 25% to 70% of patients with PsA, with some patients exclusively experiencing axial joint involvement. Early therapeutic intervention is important for preventing permanent joint and spine damage and loss of functionality in these patients. Because skin symptoms associated with psoriasis often precede psoriatic arthritis, dermatologists are uniquely positioned to play an important role in identifying and treating patients with psoriatic arthritis. Proactive screening of patients with all severities of psoriasis for the signs and symptoms of psoriatic arthritis is key to early diagnosis and intervention. In this review, we discuss the clinical presentation, risk factors, and treatment options for psoriatic arthritis with axial involvement, with the aim of helping dermatologists understand the disease and identify patients who might benefit from further assessment, treatment, and/or referral to a rheumatology practice.

      Key words

      Abbreviations used:

      AS (ankylosing spondylitis), axSpA (axial spondyloarthritis), DMARD (disease-modifying antirheumatic drug), HLA (human leukocyte antigen), IBD (inflammatory bowel disease), IL (interleukin), NSAID (nonsteroidal anti-inflammatory drug), PASI75 (75% improvement in the Psoriasis Area and Severity Index), PsA (psoriatic arthritis), QOL (quality of life), SpA (spondyloarthritis/spondyloarthropathies), TNF (tumor necrosis factor), TNFi (tumor necrosis factor inhibitor)
      • Psoriasis is an inflammatory immune disease associated with psoriatic arthritis, a disease that can involve peripheral and axial joints and cause permanent joint damage and loss of function if untreated.
      • Dermatologists play an important role in the early diagnosis and treatment of psoriatic arthritis by proactively screening patients with psoriasis.
      Psoriasis is a chronic, inflammatory, immune-mediated skin disorder associated with significant morbidity, reduced quality of life (QOL), and mortality
      • Helmick C.G.
      • Lee-Han H.
      • Hirsch S.C.
      • Baird T.L.
      • Bartlett C.L.
      Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys.
      • Krueger G.
      • Koo J.
      • Lebwohl M.
      • Menter A.
      • Stern R.S.
      • Rolstad T.
      The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey.
      • Rachakonda T.D.
      • Schupp C.W.
      • Armstrong A.W.
      Psoriasis prevalence among adults in the United States.
      that affects approximately 7.4 million adults in the United States.
      • Rachakonda T.D.
      • Schupp C.W.
      • Armstrong A.W.
      Psoriasis prevalence among adults in the United States.
      Comorbidities are common in patients with psoriasis, and psoriatic arthritis (PsA) is one of the most frequently observed.
      • Elmets C.A.
      • Leonardi C.L.
      • Davis D.M.R.
      • et al.
      Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.
      Approximately 25% to 30% of patients with psoriasis develop PsA,
      • Alinaghi F.
      • Calov M.
      • Kristensen L.E.
      • et al.
      Prevalence of psoriatic arthritis in patients with psoriasis: a systematic review and meta-analysis of observational and clinical studies.
      ,
      • Mease P.J.
      • Gladman D.D.
      • Papp K.A.
      • et al.
      Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics.
      an inflammatory, seronegative, musculoskeletal disease that can involve the joints, entheses, or spine.
      • Taylor W.
      • Gladman D.
      • Helliwell P.
      • et al.
      Classification criteria for psoriatic arthritis: development of new criteria from a large international study.
      Characteristics of PsA are heterogeneous and include nail and skin changes, peripheral arthritis, enthesitis, dactylitis, and axial spondyloarthritis (SpA)
      • Sieper J.
      • Poddubnyy D.
      Axial spondyloarthritis.
      ,
      • Coates L.C.
      • Helliwell P.S.
      Psoriatic arthritis: state of the art review.
      ; the symptoms can present alone or in combination with one another.
      • Coates L.C.
      • Kavanaugh A.
      • Mease P.J.
      • et al.
      Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis.
      PsA affects men and women equally, and it commonly develops when patients are 30 to 50 years old.
      • Gottlieb A.
      • Korman N.J.
      • Gordon K.B.
      • et al.
      Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.
      Like psoriasis, PsA is associated with multiple comorbidities, including cardiovascular disease, metabolic syndrome, obesity, diabetes, depression, uveitis, and anxiety.
      • Ogdie A.
      • Schwartzman S.
      • Husni M.E.
      Recognizing and managing comorbidities in psoriatic arthritis.
      PsA is a potentially erosive disease, and approximately 50% of patients exhibit structural damage and functional impairment within 2 years of initial assessment
      • Kane D.
      • Stafford L.
      • Bresnihan B.
      • FitzGerald O.
      A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience.
      ; many patients experience irreversible joint damage and disability with disease progression.
      • Husted J.A.
      • Tom B.D.
      • Farewell V.T.
      • Schentag C.T.
      • Gladman D.D.
      A longitudinal study of the effect of disease activity and clinical damage on physical function over the course of psoriatic arthritis: does the effect change over time?.
      ,
      • Mease P.
      • van der Heijde D.
      • Landewé R.
      • et al.
      Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study.
      Axial involvement occurs in 25% to 70% of patients with PsA,
      • Gottlieb A.
      • Korman N.J.
      • Gordon K.B.
      • et al.
      Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.
      ,
      • Gladman D.D.
      Axial disease in psoriatic arthritis.
      with exclusive axial involvement in 5% of patients.
      • Gottlieb A.
      • Korman N.J.
      • Gordon K.B.
      • et al.
      Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.
      Common symptoms include inflammatory back pain (eg, pain that improves with activity but worsens with rest, morning stiffness lasting >30 minutes).
      • Gottlieb A.
      • Korman N.J.
      • Gordon K.B.
      • et al.
      Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.
      ,
      • Baraliakos X.
      • Coates L.C.
      • Braun J.
      The involvement of the spine in psoriatic arthritis.
      The diagnosis is confirmed by physical examination and imaging (eg, sacroiliitis, spinal ossifications).
      • Gottlieb A.
      • Korman N.J.
      • Gordon K.B.
      • et al.
      Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.
      ,
      • Baraliakos X.
      • Coates L.C.
      • Braun J.
      The involvement of the spine in psoriatic arthritis.
      Among patients with axial PsA, cervical spinal mobility and lateral flexion significantly decrease within 5 years if untreated.
      • Chandran V.
      • Barrett J.
      • Schentag C.T.
      • Farewell V.T.
      • Gladman D.D.
      Axial psoriatic arthritis: update on a longterm prospective study.
      Additionally, sacroiliitis worsens with time; 37% and 52% of patients develop grade 2 or higher sacroiliitis within 5 and 10 years, respectively.
      • Chandran V.
      • Barrett J.
      • Schentag C.T.
      • Farewell V.T.
      • Gladman D.D.
      Axial psoriatic arthritis: update on a longterm prospective study.
      Therefore, early identification and treatment of patients with axial PsA is critical.
      Cutaneous manifestations of psoriasis can precede the onset of PsA by approximately 3 to 8 years,
      • Tascilar K.
      • Aydin S.Z.
      • Akar S.
      • et al.
      Delay between the onset of psoriasis and arthritis in PsA patients from the PsART international cohort [abstract].
      and 1% to 3% of patients with psoriasis develop PsA annually.
      • Alinaghi F.
      • Calov M.
      • Kristensen L.E.
      • et al.
      Prevalence of psoriatic arthritis in patients with psoriasis: a systematic review and meta-analysis of observational and clinical studies.
      ,
      • Christophers E.
      • Barker J.N.
      • Griffiths C.E.
      • et al.
      The risk of psoriatic arthritis remains constant following initial diagnosis of psoriasis among patients seen in European dermatology clinics.
      Therefore, dermatologists play a critical role in early detection for patients with PsA.
      • Gottlieb A.
      • Korman N.J.
      • Gordon K.B.
      • et al.
      Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.
      However, PsA is frequently underdiagnosed, with up to 41% of patients with psoriasis treated at dermatology centers having undiagnosed PsA.
      • Mease P.J.
      • Gladman D.D.
      • Papp K.A.
      • et al.
      Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics.
      ,
      • Haroon M.
      • Kirby B.
      • FitzGerald O.
      High prevalence of psoriatic arthritis in patients with severe psoriasis with suboptimal performance of screening questionnaires.
      To address this problem, the new American Academy of Dermatology/National Psoriasis Foundation guidelines emphasize the role of dermatologists in recognizing PsA and recommend proactive screening of patients.
      • Elmets C.A.
      • Leonardi C.L.
      • Davis D.M.R.
      • et al.
      Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.
      Therefore, it is important that dermatologists be familiar with the signs of PsA, including those associated with axial involvement. Here, we review axial PsA and describe its clinical presentation, risk factors, pathology, and treatment options.

      Clinical features of axial PsA

      Axial involvement in PsA usually occurs in young patients (<40 years old).
      • Jadon D.R.
      • Sengupta R.
      • Nightingale A.
      • et al.
      Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis.
      Although axial PsA had been thought to be more prevalent in men, an analysis of the US Corrona PsA/Spondyloarthritis Registry—which compared patients with PsA with and without axial involvement—found no significant differences in the proportion of men and women with axial involvement.
      • Mease P.J.
      • Palmer J.B.
      • Liu M.
      • et al.
      Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.
      Most patients with PsA have preceding psoriasis, but a small percentage (approximately 15%) have no psoriasis at diagnosis.
      • Ritchlin C.T.
      • Colbert R.A.
      • Gladman D.D.
      Psoriatic arthritis.
      That proportion may be lower if one includes inverse/intertriginous psoriasis, which occurs in less frequently examined areas of body folds.
      • Merola J.F.
      • Li T.
      • Li W.Q.
      • Cho E.
      • Qureshi A.A.
      Prevalence of psoriasis phenotypes among men and women in the USA.
      Patients with PsA can also present with enthesitis, dactylitis (sausage digit), nail changes, and peripheral arthritis.
      • Gottlieb A.
      • Korman N.J.
      • Gordon K.B.
      • et al.
      Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.
      ,
      • Jadon D.R.
      • Sengupta R.
      • Nightingale A.
      • et al.
      Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis.
      ,
      • Mease P.J.
      • Palmer J.B.
      • Liu M.
      • et al.
      Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.
      ,
      • Perez Alamino R.
      • Maldonado Cocco J.A.
      • Citera G.
      • et al.
      Differential features between primary ankylosing spondylitis and spondylitis associated with psoriasis and inflammatory bowel disease.
      Typical symptoms of axial PsA include morning back/neck stiffness that lasts longer than 30 minutes and neck or back pain that improves with activity and worsens after prolonged inactivity,
      • Gottlieb A.
      • Korman N.J.
      • Gordon K.B.
      • et al.
      Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.
      ,
      • Baraliakos X.
      • Coates L.C.
      • Braun J.
      The involvement of the spine in psoriatic arthritis.
      ,
      • Chandran V.
      • Barrett J.
      • Schentag C.T.
      • Farewell V.T.
      • Gladman D.D.
      Axial psoriatic arthritis: update on a longterm prospective study.
      ,
      • Mease P.J.
      • Palmer J.B.
      • Liu M.
      • et al.
      Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.
      which are defining features of inflammatory neck/back pain (Fig 1),
      • Rudwaleit M.
      • Metter A.
      • Listing J.
      • Sieper J.
      • Braun J.
      Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria.
      ,
      • Sieper J.
      • van der Heijde D.
      • Landewe R.
      • et al.
      New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis International Society (ASAS).
      as well as limited mobility.
      • Baraliakos X.
      • Coates L.C.
      • Braun J.
      The involvement of the spine in psoriatic arthritis.
      However, 20% of patients show no symptoms of axial involvement
      • Chandran V.
      • Barrett J.
      • Schentag C.T.
      • Farewell V.T.
      • Gladman D.D.
      Axial psoriatic arthritis: update on a longterm prospective study.
      ,
      • Queiro R.
      • Belzunegui J.
      • Gonzalez C.
      • et al.
      Clinically asymptomatic axial disease in psoriatic spondyloarthropathy. A retrospective study.
      ; these patients are usually diagnosed with PsA because they present with other PsA-related symptoms, such as dactylitis or arthritis.
      • Queiro R.
      • Belzunegui J.
      • Gonzalez C.
      • et al.
      Clinically asymptomatic axial disease in psoriatic spondyloarthropathy. A retrospective study.
      ,
      • Cohen J.M.
      • Husni M.E.
      • Qureshi A.A.
      • Merola J.F.
      Psoriatic arthritis: it's as easy as “PSA”.
      Figure thumbnail gr1
      Fig 1Characteristics of inflammatory neck or back pain and sacroiliac joint pain.
      • Rudwaleit M.
      • Metter A.
      • Listing J.
      • Sieper J.
      • Braun J.
      Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria.
      ,
      • Sieper J.
      • van der Heijde D.
      • Landewe R.
      • et al.
      New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis International Society (ASAS).
      ,
      • Williamson L.
      • Dockerty J.L.
      • Dalbeth N.
      • McNally E.
      • Ostlere S.
      • Wordsworth B.P.
      Clinical assessment of sacroiliitis and HLA-B27 are poor predictors of sacroiliitis diagnosed by magnetic resonance imaging in psoriatic arthritis.
      ,
      • van den Berg R.
      • de Hooge M.
      • Rudwaleit M.
      • et al.
      ASAS modification of the Berlin algorithm for diagnosing axial spondyloarthritis: results from the Spondyloarthritis Caught Early (SPACE)-cohort and from the Assessment of Spondyloarthritis international Society (ASAS)-cohort.
      Sacroiliitis is a common feature of axial PsA (25%-50% of patients)
      • Gladman D.D.
      Clinical, radiological, and functional assessment in psoriatic arthritis: is it different from other inflammatory joint diseases?.
      • Haroon M.
      • Winchester R.
      • Giles J.T.
      • Heffernan E.
      • FitzGerald O.
      Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.
      • Williamson L.
      • Dockerty J.L.
      • Dalbeth N.
      • McNally E.
      • Ostlere S.
      • Wordsworth B.P.
      Clinical assessment of sacroiliitis and HLA-B27 are poor predictors of sacroiliitis diagnosed by magnetic resonance imaging in psoriatic arthritis.
      and is frequently asymmetric (73% of patients).
      • Haroon M.
      • Winchester R.
      • Giles J.T.
      • Heffernan E.
      • FitzGerald O.
      Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.
      Patients may present with alternating pain over the sacroiliac joint/buttock, with the pain typically lasting longer than 20 minutes and being worse during the second half of the night (Fig 1).
      • Rudwaleit M.
      • Metter A.
      • Listing J.
      • Sieper J.
      • Braun J.
      Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria.
      ,
      • Williamson L.
      • Dockerty J.L.
      • Dalbeth N.
      • McNally E.
      • Ostlere S.
      • Wordsworth B.P.
      Clinical assessment of sacroiliitis and HLA-B27 are poor predictors of sacroiliitis diagnosed by magnetic resonance imaging in psoriatic arthritis.
      ,
      • van den Berg R.
      • de Hooge M.
      • Rudwaleit M.
      • et al.
      ASAS modification of the Berlin algorithm for diagnosing axial spondyloarthritis: results from the Spondyloarthritis Caught Early (SPACE)-cohort and from the Assessment of Spondyloarthritis international Society (ASAS)-cohort.
      Sacroiliitis can be assessed clinically by asking simple questions (eg, “Is your pain worse at night?” or “How long does your pain typically last?”) to determine if a patient's symptoms are characteristic of inflammatory sacroiliac joint pain (Fig 1).
      Comorbidities are common, with psoriasis being the most frequent (80% of patients).
      • Coates L.C.
      • Helliwell P.S.
      Psoriatic arthritis: state of the art review.
      Other comorbidities of axial PsA include uveitis and inflammatory bowel disease (IBD). Uveitis occurs in 6% to 7% of patients with PsA but is more common (up to 33%) in those with axial involvement.
      • Paiva E.S.
      • Macaluso D.C.
      • Edwards A.
      • Rosenbaum J.T.
      Characterisation of uveitis in patients with psoriatic arthritis.
      Uveitis in axial PsA is more common in men, in younger patients (aged <34 years), and in those positive for human leukocyte antigen (HLA)-B27.
      • Paiva E.S.
      • Macaluso D.C.
      • Edwards A.
      • Rosenbaum J.T.
      Characterisation of uveitis in patients with psoriatic arthritis.
      IBD occurs in 11% of patients with axial PsA and is significantly more common in patients with axial involvement than in those with peripheral-only PsA (2%).
      • Jadon D.R.
      • Sengupta R.
      • Nightingale A.
      • et al.
      Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis.

      Impact on QOL

      Axial PsA has a significant impact on QOL and is associated with worse disease than that seen in patients without axial involvement.
      • Mease P.J.
      • Palmer J.B.
      • Liu M.
      • et al.
      Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.
      In an analysis of the US Corrona Registry, patients with axial involvement had more severe skin manifestations, higher tender joint counts, more enthesitis, and worse disease activity.
      • Mease P.J.
      • Palmer J.B.
      • Liu M.
      • et al.
      Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.
      Similarly, patients with axial PsA had worse pain than patients without axial involvement and had significantly impaired physical function and QOL (P < .001).
      • Mease P.J.
      • Palmer J.B.
      • Liu M.
      • et al.
      Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.
      Patients with axial involvement also had decreased work productivity, with significantly higher proportions of missed work time (10.0% vs 3.3%), overall work impairment (32.3% vs 16.8%) and overall activity impairment (37.0% vs 18.1%; P < .001 for all). Problems with walking and self-care and feelings of anxiety and depression were also common.
      • Mease P.J.
      • Palmer J.B.
      • Liu M.
      • et al.
      Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.

      Risk factors

      Clinical factors associated with axial PsA include more-severe skin psoriasis, a young age at PsA onset, and severe peripheral arthritis. In 1 study, severe skin psoriasis (P = .041) and younger age at PsA onset (P < .001) correlated with developing sacroiliitis.
      • Haroon M.
      • Winchester R.
      • Giles J.T.
      • Heffernan E.
      • FitzGerald O.
      Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.
      Additionally, peripheral joint erosions were more common in patients with asymmetric sacroiliitis, suggesting a possible association between peripheral arthritis and axial involvement in patients with PsA.
      • Haroon M.
      • Winchester R.
      • Giles J.T.
      • Heffernan E.
      • FitzGerald O.
      Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.
      This association was further suggested by another study in which radiographic damage to peripheral joints increased the risk of developing axial PsA.
      • Chandran V.
      • Tolusso D.C.
      • Cook R.J.
      • Gladman D.D.
      Risk factors for axial inflammatory arthritis in patients with psoriatic arthritis.
      IBD, a known comorbidity of psoriasis,
      • Elmets C.A.
      • Leonardi C.L.
      • Davis D.M.R.
      • et al.
      Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.
      is also a risk factor for PsA and other SpAs, with both being more common in patients with Crohn's disease.
      • Fragoulis G.E.
      • Liava C.
      • Daoussis D.
      • Akriviadis E.
      • Garyfallos A.
      • Dimitroulas T.
      Inflammatory bowel diseases and spondyloarthropathies: from pathogenesis to treatment.
      ,
      • Halling M.L.
      • Kjeldsen J.
      • Knudsen T.
      • Nielsen J.
      • Hansen L.K.
      Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases.
      Sacroiliitis is estimated to occur in 12% to 46% of patients with IBD,
      • Fragoulis G.E.
      • Liava C.
      • Daoussis D.
      • Akriviadis E.
      • Garyfallos A.
      • Dimitroulas T.
      Inflammatory bowel diseases and spondyloarthropathies: from pathogenesis to treatment.
      and clinically silent macroscopic and microscopic colitis occur in approximately 60% of patients with axial SpA (axSpA),
      • Fragoulis G.E.
      • Liava C.
      • Daoussis D.
      • Akriviadis E.
      • Garyfallos A.
      • Dimitroulas T.
      Inflammatory bowel diseases and spondyloarthropathies: from pathogenesis to treatment.
      emphasizing the gut-axial axis. Uveitis has been identified as a risk factor for PsA, but its role as a risk factor for axial involvement remains unclear.
      • Eder L.
      • Haddad A.
      • Rosen C.F.
      • et al.
      The incidence and risk factors for psoriatic arthritis in patients with psoriasis: a prospective cohort study.
      A notable risk factor for axial PsA is the presence of HLA-B27.
      • Chandran V.
      • Tolusso D.C.
      • Cook R.J.
      • Gladman D.D.
      Risk factors for axial inflammatory arthritis in patients with psoriatic arthritis.
      ,
      • Brewerton D.A.
      • Caffrey M.
      • Nicholls A.
      • Walters D.
      • James D.C.
      HL-A 27 and arthropathies associated with ulcerative colitis and psoriasis.
      HLA-B27 is a known key genetic marker of ankylosing spondylitis (AS), is present in more than 80% of patients with AS, and is the only known genetic marker common to AS and axial PsA.
      • Feld J.
      • Chandran V.
      • Haroon N.
      • Inman R.
      • Gladman D.
      Axial disease in psoriatic arthritis and ankylosing spondylitis: a critical comparison.
      Although its prevalence is lower in patients with PsA (20%),
      • Feld J.
      • Chandran V.
      • Haroon N.
      • Inman R.
      • Gladman D.
      Axial disease in psoriatic arthritis and ankylosing spondylitis: a critical comparison.
      patients with axial PsA are significantly more likely to be HLA-B27 positive than patients without axial involvement (P < .001).
      • Jadon D.R.
      • Sengupta R.
      • Nightingale A.
      • et al.
      Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis.
      ,
      • Mease P.J.
      • Palmer J.B.
      • Liu M.
      • et al.
      Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.
      Patients with axial PsA and uveitis were also more likely to be HLA-B27 positive.
      • Paiva E.S.
      • Macaluso D.C.
      • Edwards A.
      • Rosenbaum J.T.
      Characterisation of uveitis in patients with psoriatic arthritis.
      ,
      • Queiro R.
      • Morante I.
      • Cabezas I.
      • Acasuso B.
      HLA-B27 and psoriatic disease: a modern view of an old relationship.
      Given these observations, whether HLA-B27–positive patients with psoriasis have AS or axial PsA remains a matter of debate. Interestingly, some studies have suggested that HLA-B0801 is the predominant genetic marker associated with axial PsA.
      • Haroon M.
      • Winchester R.
      • Giles J.T.
      • Heffernan E.
      • FitzGerald O.
      Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.
      ,
      • Queiro R.
      • Sarasqueta C.
      • Belzunegui J.
      • Gonzalez C.
      • Figueroa M.
      • Torre-Alonso J.C.
      Psoriatic spondyloarthropathy: a comparative study between HLA-B27 positive and HLA-B27 negative disease.
      Additional studies are needed, but testing for HLA-B27 and/or HLA-B0801 may identify patients with axial PsA. However, HLA-B27 testing is not indicated for all patients with suspected PsA.

      Diagnosis of axial disease in PsA

      To aid nonrheumatologist clinicians in identifying patients with PsA, several simple and easy-to-administer screening questionnaires have been developed, including the Psoriasis Epidemiology Screening Tool (Fig 2),
      • Ibrahim G.H.
      • Buch M.H.
      • Lawson C.
      • Waxman R.
      • Helliwell P.S.
      Evaluation of an existing screening tool for psoriatic arthritis in people with psoriasis and the development of a new instrument: the Psoriasis Epidemiology Screening Tool (PEST) questionnaire.
      the Toronto Psoriatic Arthritis Screen (Fig 3),
      • Gladman D.D.
      • Schentag C.T.
      • Tom B.D.
      • et al.
      Development and initial validation of a screening questionnaire for psoriatic arthritis: the Toronto Psoriatic Arthritis Screen (ToPAS).
      the Psoriatic Arthritis Screening and Evaluation (Fig 4),
      • Dominguez P.L.
      • Husni M.E.
      • Holt E.W.
      • Tyler S.
      • Qureshi A.A.
      Validity, reliability, and sensitivity-to-change properties of the psoriatic arthritis screening and evaluation questionnaire.
      and Early Arthritis for Psoriatic Patients (Fig 4).
      • Tinazzi I.
      • Adami S.
      • Zanolin E.M.
      • et al.
      The early psoriatic arthritis screening questionnaire: a simple and fast method for the identification of arthritis in patients with psoriasis.
      These questionnaires help identify symptoms associated with inflammatory arthritis (eg, swelling/stiffness) and PsA (sausage digit) that might suggest referral to a rheumatologist. Although these tools are not specific for axial PsA, they can capture some information on axial disease. For example, the Toronto Psoriatic Arthritis Screen asks about back/neck pain and stiffness history, the Psoriatic Arthritis Screening and Evaluation asks about current back pain, and Early Arthritis for Psoriatic Patients asks about nocturnal back pain. The Psoriasis Epidemiology Screening Tool does not include questions about axial disease, but the accompanying figure allows patients to mark any joints in the neck, upper/lower portions of the back, or hips that have caused discomfort; however, the figure is not commonly used in clinical practice. Because most of these tools are not free and take time to administer, patients may not always be screened during medical visits. Additionally, these tools have been found to have only moderate accuracy (sensitivity, 65%-87%; specificity, 34%-85%).
      • Iragorri N.
      • Hazlewood G.
      • Manns B.
      • Danthurebandara V.
      • Spackman E.
      Psoriatic arthritis screening: a systematic review and meta-analysis.
      ,
      • Karreman M.C.
      • Weel A.
      • van der Ven M.
      • et al.
      Performance of screening tools for psoriatic arthritis: a cross-sectional study in primary care.
      To help improve screening, we have previously proposed using the mnemonic PSA (for joint pain, stiffness after a period of inactivity/sausage digit [dactylitis], axial involvement) before a formal screening (Fig 5).
      • Cohen J.M.
      • Husni M.E.
      • Qureshi A.A.
      • Merola J.F.
      Psoriatic arthritis: it's as easy as “PSA”.
      The presence of 2 of these features suggests PsA; stiffness (S) and axial involvement (A) suggest axial PsA and should lead to formal screening and/or referral to a rheumatologist.
      Figure thumbnail gr2
      Fig 2The PEST screening questionnaire.
      • Ibrahim G.H.
      • Buch M.H.
      • Lawson C.
      • Waxman R.
      • Helliwell P.S.
      Evaluation of an existing screening tool for psoriatic arthritis in people with psoriasis and the development of a new instrument: the Psoriasis Epidemiology Screening Tool (PEST) questionnaire.
      Each positive answer is assigned 1 point. A total of 3 or more points indicates psoriatic arthritis. The axial joints that might be affected are highlighted. PEST, Psoriasis Epidemiology Screening Tool.
      (Reproduced from Ibrahim et al. Clin Exp Rheumatol 2009;27:469-74. Copyright Clinical and Experimental Rheumatology 2009.
      • Ibrahim G.H.
      • Buch M.H.
      • Lawson C.
      • Waxman R.
      • Helliwell P.S.
      Evaluation of an existing screening tool for psoriatic arthritis in people with psoriasis and the development of a new instrument: the Psoriasis Epidemiology Screening Tool (PEST) questionnaire.
      )
      Figure thumbnail gr3
      Fig 3The Toronto Psoriatic Arthritis Screen.
      • Gladman D.D.
      • Schentag C.T.
      • Tom B.D.
      • et al.
      Development and initial validation of a screening questionnaire for psoriatic arthritis: the Toronto Psoriatic Arthritis Screen (ToPAS).
      A score of 8 or more points indicates psoriatic arthritis. The questions that refer to axial involvement are highlighted. Not available for free.
      (Reproduced from Gladman et al
      • Gladman D.D.
      • Schentag C.T.
      • Tom B.D.
      • et al.
      Development and initial validation of a screening questionnaire for psoriatic arthritis: the Toronto Psoriatic Arthritis Screen (ToPAS).
      with permission from BMJ Publishing Group Ltd and the European League Against Rheumatism.)
      Figure thumbnail gr4
      Fig 4The PASE and EARP questionnaires.
      • Dominguez P.L.
      • Husni M.E.
      • Holt E.W.
      • Tyler S.
      • Qureshi A.A.
      Validity, reliability, and sensitivity-to-change properties of the psoriatic arthritis screening and evaluation questionnaire.
      ,
      • Tinazzi I.
      • Adami S.
      • Zanolin E.M.
      • et al.
      The early psoriatic arthritis screening questionnaire: a simple and fast method for the identification of arthritis in patients with psoriasis.
      Questions that can help identify axial involvement are highlighted. Questionnaires not available for free. EARP, Early Arthritis for Psoriatic Patients; PASE, Psoriatic Arthritis Screening and Evaluation.
      Figure thumbnail gr5
      Fig 5Psoriatic arthritis mnemonic: It's as easy as PSA.
      • Cohen J.M.
      • Husni M.E.
      • Qureshi A.A.
      • Merola J.F.
      Psoriatic arthritis: it's as easy as “PSA”.
      (Photograph of the hand showing dactylitis reproduced with permission of Dove Medical Press from Yamamoto T. Optimal management of dactylitis in patients with psoriatic arthritis. Open Access Rheumatol 2015;7:55-62.)

      Juvenile axial PsA

      PsA may also develop in children, with axial involvement occurring in approximately 20% of patients and being more common in later-onset than in early-onset juvenile PsA.
      • Zisman D.
      • Gladman D.D.
      • Stoll M.L.
      • et al.
      The juvenile psoriatic arthritis cohort in the CARRA registry: clinical characteristics, classification, and outcomes.
      Findings from the Childhood Arthritis and Rheumatology Research Alliance patient registry suggest that juvenile PsA is an aggressive disease; 24.6% of children have joint damage 4.6 years after symptom onset, despite more than 50% of patients being treated with a biologic disease-modifying anti-rheumatic drug (DMARD).
      • Zisman D.
      • Gladman D.D.
      • Stoll M.L.
      • et al.
      The juvenile psoriatic arthritis cohort in the CARRA registry: clinical characteristics, classification, and outcomes.
      Although juvenile SpA is more common in boys and is associated with HLA-B27,
      • Goirand M.
      • Breton S.
      • Chevallier F.
      • et al.
      Clinical features of children with enthesitis-related juvenile idiopathic arthritis/juvenile spondyloarthritis followed in a French tertiary care pediatric rheumatology centre.
      juvenile PsA is more common in girls and is not significantly associated with HLA-B27.
      • Zisman D.
      • Gladman D.D.
      • Stoll M.L.
      • et al.
      The juvenile psoriatic arthritis cohort in the CARRA registry: clinical characteristics, classification, and outcomes.
      Uveitis, one of the criteria for enthesitis/spondylitis-related juvenile idiopathic arthritis,
      • Martini A.
      • Ravelli A.
      • Avcin T.
      • et al.
      Toward new classification criteria for juvenile idiopathic arthritis: first steps, Pediatric Rheumatology International Trials Organization international consensus.
      was present in 11% of patients with juvenile PsA compared with 24% of patients with juvenile SpA and 9% of those with juvenile peripheral PsA.
      • Hayworth J.L.
      • Turk M.A.
      • Nevskaya T.
      • Pope J.E.
      The frequency of uveitis in patients with juvenile inflammatory rheumatic diseases.

      Pathogenesis

      The trigger for inflammation in axial PsA remains unknown; however, evidence suggests a role for the interleukin (IL) 23/IL-17 pathway. Dysregulation of the IL-23/IL-17 axis has been observed in patients with axSpA and those with AS.
      • Wendling D.
      Interleukin-17 targeted therapies in axial spondyloarthritis.
      ,
      • McGonagle D.G.
      • McInnes I.B.
      • Kirkham B.W.
      • Sherlock J.
      • Moots R.
      The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies.
      In addition, preclinical studies have shown that genes associated with axial disease, such as HLA-B27, may contribute to excess tumor necrosis factor-α (TNFα) and IL-17 production.
      • Glatigny S.
      • Fert I.
      • Blaton M.A.
      • et al.
      Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritis-prone HLA-B27-transgenic rats.
      Therefore, development of therapies for axial PsA has focused on TNF inhibitors (TNFis) and agents targeting molecules in the IL-23/IL-17 pathway.

      Treatment

      Treatment is based on international guidelines developed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the European League Against Rheumatism, Assessment of SpondyloArthritis International Society–European League Against Rheumatism, and the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network.
      • Coates L.C.
      • Kavanaugh A.
      • Mease P.J.
      • et al.
      Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis.
      ,
      • Gossec L.
      • Smolen J.S.
      • Ramiro S.
      • et al.
      European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.
      • van der Heijde D.
      • Ramiro S.
      • Landewé R.
      • et al.
      2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.
      • Ward M.M.
      • Deodhar A.
      • Akl E.A.
      • et al.
      American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis.
      Most of the evidence supporting treatment recommendations for axial PsA is derived from studies in AS. Goals of treatment include reducing pain, stiffness, and fatigue; improving and maintaining spinal flexibility and normal posture; improving functional capability; and maintaining the ability to work, with a target of remission or minimal/low disease activity.
      • Coates L.C.
      • Kavanaugh A.
      • Mease P.J.
      • et al.
      Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis.
      ,
      • Gossec L.
      • Smolen J.S.
      • Ramiro S.
      • et al.
      European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.
      • van der Heijde D.
      • Ramiro S.
      • Landewé R.
      • et al.
      2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.
      • Ward M.M.
      • Deodhar A.
      • Akl E.A.
      • et al.
      American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis.
      Nonsteroidal anti-inflammatory drugs (NSAIDS) are the first-line recommended treatment for pain and stiffness.
      • Coates L.C.
      • Kavanaugh A.
      • Mease P.J.
      • et al.
      Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis.
      ,
      • Gossec L.
      • Smolen J.S.
      • Ramiro S.
      • et al.
      European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.
      • van der Heijde D.
      • Ramiro S.
      • Landewé R.
      • et al.
      2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.
      • Ward M.M.
      • Deodhar A.
      • Akl E.A.
      • et al.
      American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis.
      Physiotherapy and sacroiliac joint injections (if appropriate) can also be part of the initial treatment approach; however, patients should not be treated long term with systemic glucocorticoids. If symptoms are not controlled by NSAIDs, or if patients have high disease activity, the guidelines recommend initiation of biologic DMARDs. However, conventional DMARDs (eg, methotrexate) are not routinely prescribed for patients with axial disease because they are not efficacious.
      • van der Heijde D.
      • Ramiro S.
      • Landewé R.
      • et al.
      2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.
      TNFis are usually recommended in patients who do not respond to or are intolerant of NSAIDs.
      • Coates L.C.
      • Kavanaugh A.
      • Mease P.J.
      • et al.
      Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis.
      ,
      • Gossec L.
      • Smolen J.S.
      • Ramiro S.
      • et al.
      European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.
      • van der Heijde D.
      • Ramiro S.
      • Landewé R.
      • et al.
      2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.
      • Ward M.M.
      • Deodhar A.
      • Akl E.A.
      • et al.
      American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis.
      No data show the efficacy of TNFis specifically in patients with axial PsA; however, a meta-analysis found that TNFis improved disease activity and functional capacity in both patients with AS and those with nonradiographic axSpA.
      • Callhoff J.
      • Sieper J.
      • Weiss A.
      • Zink A.
      • Listing J.
      Efficacy of TNFalpha blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis.
      Available TNFis include adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab.
      • Coates L.C.
      • Kavanaugh A.
      • Mease P.J.
      • et al.
      Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis.
      ,
      • Gossec L.
      • Smolen J.S.
      • Ramiro S.
      • et al.
      European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.
      • van der Heijde D.
      • Ramiro S.
      • Landewé R.
      • et al.
      2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.
      • Ward M.M.
      • Deodhar A.
      • Akl E.A.
      • et al.
      American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis.
      No TNFi is recommended over another, although monoclonal antibodies (eg, infliximab, certolizumab pegol, or adalimumab [which is approved in the United States for uveitis]) are recommended over etanercept in patients with IBD or recurrent iritis.
      • van der Heijde D.
      • Ramiro S.
      • Landewé R.
      • et al.
      2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.
      ,
      • Ward M.M.
      • Deodhar A.
      • Akl E.A.
      • et al.
      American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis.
      ,
      • Menter A.
      • Strober B.E.
      • Kaplan D.H.
      • et al.
      Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.
      Furthermore, etanercept is less effective for skin clearance in patients with PsA and psoriasis: at 24 weeks, a 75% improvement in the Psoriasis Area and Severity Index (PASI75) was achieved by only 23% of patients using etanercept,
      • Mease P.J.
      • Kivitz A.J.
      • Burch F.X.
      • et al.
      Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression.
      whereas PASI75 rates in trials of other TNFis have been in the range of 59% to 65%.
      • Mease P.J.
      • Gladman D.D.
      • Ritchlin C.T.
      • et al.
      Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial.
      • Mease P.J.
      • Fleischmann R.
      • Deodhar A.A.
      • et al.
      Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a phase 3 double-blind randomised placebo-controlled study (RAPID-PsA).
      • Antoni C.
      • Krueger G.G.
      • de Vlam K.
      • et al.
      Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial.
      • Kavanaugh A.
      • Husni M.E.
      • Harrison D.D.
      • et al.
      Safety and efficacy of intravenous golimumab in patients with active psoriatic arthritis: results through week twenty-four of the GO-VIBRANT study.
      Etanercept is also associated with lower PASI75 rates in patients with psoriasis (49% at week 12)
      • Leonardi C.L.
      • Powers J.L.
      • Matheson R.T.
      • et al.
      Etanercept as monotherapy in patients with psoriasis.
      ; in contrast, PASI75 rates with infliximab, certolizumab pegol, and adalimumab have ranged from 71% to 88% (week 10 or 16).
      • Gottlieb A.B.
      • Evans R.
      • Li S.
      • et al.
      Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial.
      • Menter A.
      • Tyring S.K.
      • Gordon K.
      • et al.
      Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial.
      • Gottlieb A.B.
      • Blauvelt A.
      • Thaci D.
      • et al.
      Certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2).
      Interestingly, very little variability has been observed in the proportion of patients achieving a 20% improvement in the American College of Rheumatology response criteria in patients with PsA treated with these 4 agents (52%-59%).
      • Mease P.J.
      • Kivitz A.J.
      • Burch F.X.
      • et al.
      Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression.
      • Mease P.J.
      • Gladman D.D.
      • Ritchlin C.T.
      • et al.
      Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial.
      • Mease P.J.
      • Fleischmann R.
      • Deodhar A.A.
      • et al.
      Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a phase 3 double-blind randomised placebo-controlled study (RAPID-PsA).
      • Antoni C.
      • Krueger G.G.
      • de Vlam K.
      • et al.
      Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial.
      However, approximately 40% of patients do not respond to TNFi therapy.
      • Noureldin B.
      • Barkham N.
      The current standard of care and the unmet needs for axial spondyloarthritis.
      In these cases, patients can switch to a different TNFi
      • van der Heijde D.
      • Ramiro S.
      • Landewé R.
      • et al.
      2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.
      ; however, efficacy may be lower than that with the first TNFi.
      • Lie E.
      • van der Heijde D.
      • Uhlig T.
      • et al.
      Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register.
      Studies in AS also suggested that IL-17 inhibitors could be effective in treating axial PsA.
      • Baeten D.
      • Sieper J.
      • Braun J.
      • et al.
      Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis.
      The phase 3 studies MEASURE1 (16 Week Efficacy and 2 Year Long Term Safety and Efficacy of Secukinumab in Patients With Active Ankylosing Spondylitis) (N = 371) and MEASURE2 (16 Week Efficacy and 5 Year Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Ankylosing Spondylitis) (N = 219) showed that secukinumab, a selective IL-17A inhibitor, was superior to placebo in reducing signs and symptoms of AS.
      • Baeten D.
      • Sieper J.
      • Braun J.
      • et al.
      Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis.
      ,
      • Braun J.
      • Baraliakos X.
      • Deodhar A.
      • et al.
      Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4-year results from the MEASURE 1 study.
      To determine efficacy specifically in axial PsA, secukinumab was evaluated in MAXIMISE (Study of the Efficacy and Safety of Secukinumab in Participants With Active Psoriatic Arthritis With Axial Skeleton Involvement) (N = 498), the first randomized controlled study to evaluate a biologic in axial PsA.
      • Baraliakos X.
      • Coates L.C.
      • Gossec L.
      • et al.
      Secukinumab improves axial manifestations in patients with psoriatic arthritis and inadequate response to NSAIDs: primary analysis of the MAXIMISE trial.
      Patients with axial PsA and inadequate response to NSAIDs were randomized to secukinumab 300 mg, secukinumab 150 mg, or placebo. Secukinumab provided rapid and significant improvement of axial function and symptoms versus placebo, with the proportion of patients achieving an Assessment of SpondyloArthritis International Society 20% response at week 12 being 63.1% with secukinumab 300 mg and 66.3% with secukinumab 150 mg versus 31.3% with placebo (P < .0001).
      • Baraliakos X.
      • Coates L.C.
      • Gossec L.
      • et al.
      Secukinumab improves axial manifestations in patients with psoriatic arthritis and inadequate response to NSAIDs: primary analysis of the MAXIMISE trial.
      The safety profile was similar across groups, and IBD was uncommon in patients with PsA or AS treated with secukinumab.
      • Schreiber S.
      • Colombel J.F.
      • Feagan B.G.
      • et al.
      Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials.
      Ixekizumab, a second IL-17A inhibitor, is also approved for PsA and was recently approved for AS, suggesting that ixekizumab could benefit patients with axial PsA. Ixekizumab led to clinical improvement and was better than placebo at improving AS in patients who were naive to biologic DMARDs (COAST-V [A Study of Ixekizumab (LY2439821) in bDMARD-Naive Participants With Radiographic Axial Spondyloarthritis] [N = 341])
      • van der Heijde D.
      • Cheng-Chung Wei J.
      • Dougados M.
      • et al.
      Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial.
      and in those previously treated with TNFis (COAST-W [A Study of Ixekizumab (LY2439821) in TNF Inhibitor Experienced Participants With Radiographic Axial Spondyloarthritis] [N = 316]).
      • Deodhar A.
      • Poddubnyy D.
      • Pacheco-Tena C.
      • et al.
      Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: sixteen-week results from a phase III randomized, double-blind, placebo-controlled trial in patients with prior inadequate response to or intolerance of tumor necrosis factor inhibitors.
      Injection-site reactions, upper respiratory tract infections, and nasopharyngitis were common adverse events. Although these findings are promising for the treatment of axial PsA, ixekizumab had not been evaluated specifically in axial PsA at the time of this writing.
      Findings from an open-label proof-of-concept study suggested that ustekinumab, an antibody targeting IL-12 and IL-23, might be efficacious in AS.
      • Poddubnyy D.
      • Hermann K.G.
      • Callhoff J.
      • Listing J.
      • Sieper J.
      Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS).
      Ustekinumab was associated with a reduction in symptoms of active disease, with 35% of patients achieving inactive disease after 24 weeks of treatment. However, subsequent phase 3 studies evaluating ustekinumab in patients with radiographic or nonradiographic axSpA were terminated because ustekinumab did not achieve key endpoints.
      • Deodhar A.
      • Gensler L.S.
      • Sieper J.
      • et al.
      Three multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of ustekinumab in axial spondyloarthritis.
      Similarly, treatment with risankizumab, a p19/IL-23 inhibitor, did not lead to clinically meaningful improvements versus placebo in patients with active AS.
      • Baeten D.
      • Ostergaard M.
      • Wei J.C.
      • et al.
      Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study.
      These findings suggest that IL-23 may not be a relevant target in patients with axial PsA.

      Conclusions

      PsA, with or without axial involvement, is an underdiagnosed and potentially debilitating disease that greatly reduces patients' functioning and QOL. Early and appropriate treatment is essential in delaying structural joint damage and maintaining patient QOL and well-being. Dermatologists play a crucial role in detecting PsA in their patients and in treating or promptly referring patients to a rheumatologist. Therefore, it is important for dermatologists to proactively screen patients with psoriasis for symptoms of PsA and to understand how to identify signs of axial involvement in PsA (Fig 2, Fig 3, Fig 4, Fig 5), especially inflammatory back pain (Fig 1). Dermatologists are encouraged to partner with patients, rheumatologists, and other specialists to achieve optimal patient management.
      The authors thank Karen Chinchilla, PhD, of ArticulateScience LLC, Hamilton, NJ, for providing medical writing support/editorial support, which was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

      References

        • Helmick C.G.
        • Lee-Han H.
        • Hirsch S.C.
        • Baird T.L.
        • Bartlett C.L.
        Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys.
        Am J Prev Med. 2014; 47: 37-45
        • Krueger G.
        • Koo J.
        • Lebwohl M.
        • Menter A.
        • Stern R.S.
        • Rolstad T.
        The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey.
        Arch Dermatol. 2001; 137: 280-284
        • Rachakonda T.D.
        • Schupp C.W.
        • Armstrong A.W.
        Psoriasis prevalence among adults in the United States.
        J Am Acad Dermatol. 2014; 70: 512-516
        • Elmets C.A.
        • Leonardi C.L.
        • Davis D.M.R.
        • et al.
        Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.
        J Am Acad Dermatol. 2019; 80: 1073-1113
        • Alinaghi F.
        • Calov M.
        • Kristensen L.E.
        • et al.
        Prevalence of psoriatic arthritis in patients with psoriasis: a systematic review and meta-analysis of observational and clinical studies.
        J Am Acad Dermatol. 2019; 80: 251-265
        • Mease P.J.
        • Gladman D.D.
        • Papp K.A.
        • et al.
        Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics.
        J Am Acad Dermatol. 2013; 69: 729-735
        • Taylor W.
        • Gladman D.
        • Helliwell P.
        • et al.
        Classification criteria for psoriatic arthritis: development of new criteria from a large international study.
        Arthritis Rheum. 2006; 54: 2665-2673
        • Sieper J.
        • Poddubnyy D.
        Axial spondyloarthritis.
        Lancet. 2017; 390: 73-84
        • Coates L.C.
        • Helliwell P.S.
        Psoriatic arthritis: state of the art review.
        Clin Med (Lond). 2017; 17: 65-70
        • Coates L.C.
        • Kavanaugh A.
        • Mease P.J.
        • et al.
        Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis.
        Arthritis Rheumatol. 2016; 68: 1060-1071
        • Gottlieb A.
        • Korman N.J.
        • Gordon K.B.
        • et al.
        Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.
        J Am Acad Dermatol. 2008; 58: 851-864
        • Ogdie A.
        • Schwartzman S.
        • Husni M.E.
        Recognizing and managing comorbidities in psoriatic arthritis.
        Curr Opin Rheumatol. 2015; 27: 118-126
        • Kane D.
        • Stafford L.
        • Bresnihan B.
        • FitzGerald O.
        A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience.
        Rheumatology (Oxford). 2003; 42: 1460-1468
        • Husted J.A.
        • Tom B.D.
        • Farewell V.T.
        • Schentag C.T.
        • Gladman D.D.
        A longitudinal study of the effect of disease activity and clinical damage on physical function over the course of psoriatic arthritis: does the effect change over time?.
        Arthritis Rheum. 2007; 56: 840-849
        • Mease P.
        • van der Heijde D.
        • Landewé R.
        • et al.
        Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study.
        Ann Rheum Dis. 2018; 77: 890-897
        • Gladman D.D.
        Axial disease in psoriatic arthritis.
        Curr Rheumatol Rep. 2007; 9: 455-460
        • Baraliakos X.
        • Coates L.C.
        • Braun J.
        The involvement of the spine in psoriatic arthritis.
        Clin Exp Rheumatol. 2015; 33: S31-S35
        • Chandran V.
        • Barrett J.
        • Schentag C.T.
        • Farewell V.T.
        • Gladman D.D.
        Axial psoriatic arthritis: update on a longterm prospective study.
        J Rheumatol. 2009; 36: 2744-2750
        • Tascilar K.
        • Aydin S.Z.
        • Akar S.
        • et al.
        Delay between the onset of psoriasis and arthritis in PsA patients from the PsART international cohort [abstract].
        Arthritis Rheumatol. 2019; 71: 2854
        • Christophers E.
        • Barker J.N.
        • Griffiths C.E.
        • et al.
        The risk of psoriatic arthritis remains constant following initial diagnosis of psoriasis among patients seen in European dermatology clinics.
        J Eur Acad Dermatol Venereol. 2010; 24: 548-554
        • Haroon M.
        • Kirby B.
        • FitzGerald O.
        High prevalence of psoriatic arthritis in patients with severe psoriasis with suboptimal performance of screening questionnaires.
        Ann Rheum Dis. 2013; 72: 736-740
        • Jadon D.R.
        • Sengupta R.
        • Nightingale A.
        • et al.
        Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis.
        Ann Rheum Dis. 2017; 76: 701-707
        • Mease P.J.
        • Palmer J.B.
        • Liu M.
        • et al.
        Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.
        J Rheumatol. 2018; 45: 1389-1396
        • Ritchlin C.T.
        • Colbert R.A.
        • Gladman D.D.
        Psoriatic arthritis.
        N Engl J Med. 2017; 376: 957-970
        • Merola J.F.
        • Li T.
        • Li W.Q.
        • Cho E.
        • Qureshi A.A.
        Prevalence of psoriasis phenotypes among men and women in the USA.
        Clin Exp Dermatol. 2016; 41: 486-489
        • Perez Alamino R.
        • Maldonado Cocco J.A.
        • Citera G.
        • et al.
        Differential features between primary ankylosing spondylitis and spondylitis associated with psoriasis and inflammatory bowel disease.
        J Rheumatol. 2011; 38: 1656-1660
        • Rudwaleit M.
        • Metter A.
        • Listing J.
        • Sieper J.
        • Braun J.
        Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria.
        Arthritis Rheum. 2006; 54: 569-578
        • Sieper J.
        • van der Heijde D.
        • Landewe R.
        • et al.
        New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis International Society (ASAS).
        Ann Rheum Dis. 2009; 68: 784-788
        • Queiro R.
        • Belzunegui J.
        • Gonzalez C.
        • et al.
        Clinically asymptomatic axial disease in psoriatic spondyloarthropathy. A retrospective study.
        Clin Rheumatol. 2002; 21: 10-13
        • Cohen J.M.
        • Husni M.E.
        • Qureshi A.A.
        • Merola J.F.
        Psoriatic arthritis: it's as easy as “PSA”.
        J Am Acad Dermatol. 2015; 72: 905-906
        • Gladman D.D.
        Clinical, radiological, and functional assessment in psoriatic arthritis: is it different from other inflammatory joint diseases?.
        Ann Rheum Dis. 2006; 65: iii22-iii24
        • Haroon M.
        • Winchester R.
        • Giles J.T.
        • Heffernan E.
        • FitzGerald O.
        Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.
        Clin Exp Rheumatol. 2017; 35: 270-276
        • Williamson L.
        • Dockerty J.L.
        • Dalbeth N.
        • McNally E.
        • Ostlere S.
        • Wordsworth B.P.
        Clinical assessment of sacroiliitis and HLA-B27 are poor predictors of sacroiliitis diagnosed by magnetic resonance imaging in psoriatic arthritis.
        Rheumatology (Oxford). 2004; 43: 85-88
        • van den Berg R.
        • de Hooge M.
        • Rudwaleit M.
        • et al.
        ASAS modification of the Berlin algorithm for diagnosing axial spondyloarthritis: results from the Spondyloarthritis Caught Early (SPACE)-cohort and from the Assessment of Spondyloarthritis international Society (ASAS)-cohort.
        Ann Rheum Dis. 2013; 72: 1646-1653
        • Paiva E.S.
        • Macaluso D.C.
        • Edwards A.
        • Rosenbaum J.T.
        Characterisation of uveitis in patients with psoriatic arthritis.
        Ann Rheum Dis. 2000; 59: 67-70
        • Chandran V.
        • Tolusso D.C.
        • Cook R.J.
        • Gladman D.D.
        Risk factors for axial inflammatory arthritis in patients with psoriatic arthritis.
        J Rheumatol. 2010; 37: 809-815
        • Fragoulis G.E.
        • Liava C.
        • Daoussis D.
        • Akriviadis E.
        • Garyfallos A.
        • Dimitroulas T.
        Inflammatory bowel diseases and spondyloarthropathies: from pathogenesis to treatment.
        World J Gastroenterol. 2019; 25: 2162-2176
        • Halling M.L.
        • Kjeldsen J.
        • Knudsen T.
        • Nielsen J.
        • Hansen L.K.
        Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases.
        World J Gastroenterol. 2017; 23: 6137-6146
        • Eder L.
        • Haddad A.
        • Rosen C.F.
        • et al.
        The incidence and risk factors for psoriatic arthritis in patients with psoriasis: a prospective cohort study.
        Arthritis Rheumatol. 2016; 68: 915-923
        • Brewerton D.A.
        • Caffrey M.
        • Nicholls A.
        • Walters D.
        • James D.C.
        HL-A 27 and arthropathies associated with ulcerative colitis and psoriasis.
        Lancet. 1974; 1: 956-958
        • Feld J.
        • Chandran V.
        • Haroon N.
        • Inman R.
        • Gladman D.
        Axial disease in psoriatic arthritis and ankylosing spondylitis: a critical comparison.
        Nat Rev Rheumatol. 2018; 14: 363-371
        • Queiro R.
        • Morante I.
        • Cabezas I.
        • Acasuso B.
        HLA-B27 and psoriatic disease: a modern view of an old relationship.
        Rheumatology (Oxford). 2016; 55: 221-229
        • Queiro R.
        • Sarasqueta C.
        • Belzunegui J.
        • Gonzalez C.
        • Figueroa M.
        • Torre-Alonso J.C.
        Psoriatic spondyloarthropathy: a comparative study between HLA-B27 positive and HLA-B27 negative disease.
        Semin Arthritis Rheum. 2002; 31: 413-418
        • Ibrahim G.H.
        • Buch M.H.
        • Lawson C.
        • Waxman R.
        • Helliwell P.S.
        Evaluation of an existing screening tool for psoriatic arthritis in people with psoriasis and the development of a new instrument: the Psoriasis Epidemiology Screening Tool (PEST) questionnaire.
        Clin Exp Rheumatol. 2009; 27: 469-474
        • Gladman D.D.
        • Schentag C.T.
        • Tom B.D.
        • et al.
        Development and initial validation of a screening questionnaire for psoriatic arthritis: the Toronto Psoriatic Arthritis Screen (ToPAS).
        Ann Rheum Dis. 2009; 68: 497-501
        • Dominguez P.L.
        • Husni M.E.
        • Holt E.W.
        • Tyler S.
        • Qureshi A.A.
        Validity, reliability, and sensitivity-to-change properties of the psoriatic arthritis screening and evaluation questionnaire.
        Arch Dermatol Res. 2009; 301: 573-579
        • Tinazzi I.
        • Adami S.
        • Zanolin E.M.
        • et al.
        The early psoriatic arthritis screening questionnaire: a simple and fast method for the identification of arthritis in patients with psoriasis.
        Rheumatology (Oxford). 2012; 51: 2058-2063
        • Iragorri N.
        • Hazlewood G.
        • Manns B.
        • Danthurebandara V.
        • Spackman E.
        Psoriatic arthritis screening: a systematic review and meta-analysis.
        Rheumatology (Oxford). 2019; 58: 692-707
        • Karreman M.C.
        • Weel A.
        • van der Ven M.
        • et al.
        Performance of screening tools for psoriatic arthritis: a cross-sectional study in primary care.
        Rheumatology (Oxford). 2017; 56: 597-602
        • Zisman D.
        • Gladman D.D.
        • Stoll M.L.
        • et al.
        The juvenile psoriatic arthritis cohort in the CARRA registry: clinical characteristics, classification, and outcomes.
        J Rheumatol. 2017; 44: 342-351
        • Goirand M.
        • Breton S.
        • Chevallier F.
        • et al.
        Clinical features of children with enthesitis-related juvenile idiopathic arthritis/juvenile spondyloarthritis followed in a French tertiary care pediatric rheumatology centre.
        Pediatr Rheumatol Online J. 2018; 16: 21
        • Martini A.
        • Ravelli A.
        • Avcin T.
        • et al.
        Toward new classification criteria for juvenile idiopathic arthritis: first steps, Pediatric Rheumatology International Trials Organization international consensus.
        J Rheumatol. 2019; 46: 190-197
        • Hayworth J.L.
        • Turk M.A.
        • Nevskaya T.
        • Pope J.E.
        The frequency of uveitis in patients with juvenile inflammatory rheumatic diseases.
        Joint Bone Spine. 2019; 86: 685-690
        • Wendling D.
        Interleukin-17 targeted therapies in axial spondyloarthritis.
        Immunotherapy. 2015; 7: 1125-1128
        • McGonagle D.G.
        • McInnes I.B.
        • Kirkham B.W.
        • Sherlock J.
        • Moots R.
        The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies.
        Ann Rheum Dis. 2019; 78: 1167-1178
        • Glatigny S.
        • Fert I.
        • Blaton M.A.
        • et al.
        Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritis-prone HLA-B27-transgenic rats.
        Arthritis Rheum. 2012; 64: 110-120
        • Gossec L.
        • Smolen J.S.
        • Ramiro S.
        • et al.
        European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.
        Ann Rheum Dis. 2016; 75: 499-510
        • van der Heijde D.
        • Ramiro S.
        • Landewé R.
        • et al.
        2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.
        Ann Rheum Dis. 2017; 76: 978-991
        • Ward M.M.
        • Deodhar A.
        • Akl E.A.
        • et al.
        American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis.
        Arthritis Rheum. 2016; 68: 282-298
        • Callhoff J.
        • Sieper J.
        • Weiss A.
        • Zink A.
        • Listing J.
        Efficacy of TNFalpha blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis.
        Ann Rheum Dis. 2015; 74: 1241-1248
        • Menter A.
        • Strober B.E.
        • Kaplan D.H.
        • et al.
        Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.
        J Am Acad Dermatol. 2019; 80: 1029-1072
        • Mease P.J.
        • Kivitz A.J.
        • Burch F.X.
        • et al.
        Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression.
        Arthritis Rheum. 2004; 50: 2264-2272
        • Mease P.J.
        • Gladman D.D.
        • Ritchlin C.T.
        • et al.
        Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial.
        Arthritis Rheum. 2005; 52: 3279-3289
        • Mease P.J.
        • Fleischmann R.
        • Deodhar A.A.
        • et al.
        Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a phase 3 double-blind randomised placebo-controlled study (RAPID-PsA).
        Ann Rheum Dis. 2014; 73: 48-55
        • Antoni C.
        • Krueger G.G.
        • de Vlam K.
        • et al.
        Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial.
        Ann Rheum Dis. 2005; 64: 1150-1157
        • Kavanaugh A.
        • Husni M.E.
        • Harrison D.D.
        • et al.
        Safety and efficacy of intravenous golimumab in patients with active psoriatic arthritis: results through week twenty-four of the GO-VIBRANT study.
        Arthritis Rheumatol. 2017; 69: 2151-2161
        • Leonardi C.L.
        • Powers J.L.
        • Matheson R.T.
        • et al.
        Etanercept as monotherapy in patients with psoriasis.
        New Engl J Med. 2003; 349: 2014-2022
        • Gottlieb A.B.
        • Evans R.
        • Li S.
        • et al.
        Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial.
        J Am Acad Dermatol. 2004; 51: 534-542
        • Menter A.
        • Tyring S.K.
        • Gordon K.
        • et al.
        Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial.
        J Am Acad Dermatol. 2008; 58: 106-115
        • Gottlieb A.B.
        • Blauvelt A.
        • Thaci D.
        • et al.
        Certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2).
        J Am Acad Dermatol. 2018; 79: 302-314
        • Noureldin B.
        • Barkham N.
        The current standard of care and the unmet needs for axial spondyloarthritis.
        Rheumatology (Oxford). 2018; 57: vi10-vi17
        • Lie E.
        • van der Heijde D.
        • Uhlig T.
        • et al.
        Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register.
        Ann Rheum Dis. 2011; 70: 157-163
        • Baeten D.
        • Sieper J.
        • Braun J.
        • et al.
        Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis.
        N Engl J Med. 2015; 373: 2534-2548
        • Braun J.
        • Baraliakos X.
        • Deodhar A.
        • et al.
        Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4-year results from the MEASURE 1 study.
        Rheumatology (Oxford). 2019; 58: 859-868
        • Baraliakos X.
        • Coates L.C.
        • Gossec L.
        • et al.
        Secukinumab improves axial manifestations in patients with psoriatic arthritis and inadequate response to NSAIDs: primary analysis of the MAXIMISE trial.
        Ann Rheum Dis. 2019; 78: 195-196
        • Schreiber S.
        • Colombel J.F.
        • Feagan B.G.
        • et al.
        Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials.
        Ann Rheum Dis. 2019; 78: 473-479
        • van der Heijde D.
        • Cheng-Chung Wei J.
        • Dougados M.
        • et al.
        Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial.
        Lancet. 2018; 392: 2441-2451
        • Deodhar A.
        • Poddubnyy D.
        • Pacheco-Tena C.
        • et al.
        Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: sixteen-week results from a phase III randomized, double-blind, placebo-controlled trial in patients with prior inadequate response to or intolerance of tumor necrosis factor inhibitors.
        Arthritis Rheumatol. 2018; 71: 599-611
        • Poddubnyy D.
        • Hermann K.G.
        • Callhoff J.
        • Listing J.
        • Sieper J.
        Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS).
        Ann Rheum Dis. 2014; 73: 817-823
        • Deodhar A.
        • Gensler L.S.
        • Sieper J.
        • et al.
        Three multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of ustekinumab in axial spondyloarthritis.
        Arthritis Rheumatol. 2019; 71: 258-270
        • Baeten D.
        • Ostergaard M.
        • Wei J.C.
        • et al.
        Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study.
        Ann Rheum Dis. 2018; 77: 1295-1302