Advertisement

Representation of older adults in randomized controlled trials on systemic treatment in plaque psoriasis: A systematic review

      Background

      Psoriasis is frequently seen in older patients, and systemic treatment is often indicated. Randomized controlled trials (RCTs) generally maintain strict inclusion and exclusion criteria, which might lead to a disproportionally high exclusion rate of older adults.

      Objective

      To determine the representation of older adults (≥65 years) in RCTs studying systemic treatment in plaque psoriasis.

      Methods

      A systematic literature search was performed in PubMed/MEDLINE, Embase, and CENTRAL, including RCTs concerning systemic treatments in plaque psoriasis in the past 15 years. Direct exclusion (based on age limits) and indirect exclusion (other exclusion criteria) were assessed. Study selection and data extraction were performed by 2 independent reviewers.

      Results

      Of 162 trials reviewed in full, 54 (33.3%) maintained an upper age limit (55-85 years). Of the remaining 108 trials, 106 reported exclusion criteria and did not use an upper age limit. However, 96 (90.6%) of these trials used exclusion criteria that might unequally affect older adults. The exclusion criteria serious concurrent infection (n = 104, 66.7%) and malignancy (n = 100, 64.1%) were most commonly mentioned in the included RCTs.

      Limitations

      Only published RCTs were included.

      Conclusion

      Older adults might be poorly represented in RCTs studying systemic treatment in plaque psoriasis because of a high rate of direct and indirect exclusion.

      Key words

      Abbreviation used:

      RCT (randomized controlled trial)
      To read this article in full you will need to make a payment
      AAD Member Login
      AAD Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kim E.K.
        • Kim H.O.
        • Park Y.M.
        • Park C.J.
        • Yu D.S.
        • Lee J.Y.
        Prevalence and risk factors of depression in geriatric patients with dermatological diseases.
        Ann Dermatol. 2013; 25: 278-284
        • Shah M.
        • Coates M.
        An assessment of the quality of life in older patients with skin disease.
        Br J Dermatol. 2006; 154: 150-153
        • Armstrong A.W.
        • Schupp C.
        • Wu J.
        • Bebo B.
        Quality of life and work productivity impairment among psoriasis patients: findings from the National Psoriasis Foundation survey data 2003-2011.
        PLoS One. 2012; 7: e52935
        • Michalek I.M.
        • Loring B.
        • John S.M.
        A systematic review of worldwide epidemiology of psoriasis.
        J Eur Acad Dermatol Venereol. 2017; 31: 205-212
        • Balato N.
        • Patruno C.
        • Napolitano M.
        • Patri A.
        • Ayala F.
        • Scarpa R.
        Managing moderate-to-severe psoriasis in the elderly.
        Drugs Aging. 2014; 31: 233-238
        • Endo J.O.
        • Wong J.W.
        • Norman R.A.
        • Chang A.L.
        Geriatric dermatology: part I. Geriatric pharmacology for the dermatologist.
        J Am Acad Dermatol. 2013; 68: 521.e1-521.e10
        • Xue Q.L.
        The frailty syndrome: definition and natural history.
        Clin Geriatr Med. 2011; 27: 1-15
        • Phan C.
        • Sigal M.L.
        • Esteve E.
        • et al.
        Psoriasis in the elderly: epidemiological and clinical aspects, and evaluation of patients with very late onset psoriasis.
        J Eur Acad Dermatol Venereol. 2016; 30: 78-82
        • Lopez-Estebaranz J.L.
        • Sanchez-Carazo J.L.
        • Sulleiro S.
        Effect of a family history of psoriasis and age on comorbidities and quality of life in patients with moderate to severe psoriasis: results from the ARIZONA study.
        J Dermatol. 2016; 43: 395-401
        • Kimball A.B.
        • Leonardi C.
        • Stahle M.
        • et al.
        Demography, baseline disease characteristics and treatment history of patients with psoriasis enrolled in a multicentre, prospective, disease-based registry (PSOLAR).
        Br J Dermatol. 2014; 171: 137-147
        • Medina C.
        • Carretero G.
        • Ferrandiz C.
        • et al.
        Safety of classic and biologic systemic therapies for the treatment of psoriasis in elderly: an observational study from national BIOBADADERM registry.
        J Eur Acad Dermatol Venereol. 2015; 29: 858-864
        • Tan K.W.
        • Griffiths C.E.
        Novel systemic therapies for the treatment of psoriasis.
        Expert Opin Pharmacother. 2016; 17: 79-92
        • Cline A.
        • Cardwell L.A.
        • Feldman S.R.
        Advances in treating psoriasis in the elderly with small molecule inhibitors.
        Expert Opin Pharmacother. 2017; 18: 1965-1973
        • Zulman D.M.
        • Sussman J.B.
        • Chen X.
        • Cigolle C.T.
        • Blaum C.S.
        • Hayward R.A.
        Examining the evidence: a systematic review of the inclusion and analysis of older adults in randomized controlled trials.
        J Gen Intern Med. 2011; 26: 783-790
        • Cherubini A.
        • Oristrell J.
        • Pla X.
        • et al.
        The persistent exclusion of older patients from ongoing clinical trials regarding heart failure.
        Arch Intern Med. 2011; 171: 550-556
        • Garcia-Doval I.
        • Carretero G.
        • Vanaclocha F.
        • et al.
        Risk of serious adverse events associated with biologic and nonbiologic psoriasis systemic therapy: patients ineligible vs eligible for randomized controlled trials.
        Arch Dermatol. 2012; 148: 463-470
        • Malatestinic W.
        • Nordstrom B.
        • Wu J.J.
        • et al.
        Characteristics and medication use of psoriasis patients who may or may not qualify for randomized controlled trials.
        J Manag Care Spec Pharm. 2017; 23: 370-381
      1. Higgins J.P.T. Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. 2011 (Available from www.cochrane-handbook.org)
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        • Group P.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        PLoS Med. 2009; 6: e1000097
        • Sbidian E.
        • Chaimani A.
        • Garcia-Doval I.
        • et al.
        Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
        Cochrane Database Syst Rev. 2017; 12: CD011535
        • Masnoon N.
        • Shakib S.
        • Kalisch-Ellett L.
        • Caughey G.E.
        What is polypharmacy? A systematic review of definitions.
        BMC Geriatr. 2017; 17: 230
        • Ellis C.N.
        • Barker J.N.
        • Haig A.E.
        • Parker C.A.
        • Daly S.
        • Jayawardene D.A.
        Placebo response in two long-term randomized psoriasis studies that were negative for rosiglitazone.
        Am J Clin Dermatol. 2007; 8: 93-102
        • Langley R.G.
        • Elewski B.E.
        • Lebwohl M.
        • et al.
        Secukinumab in plaque psoriasis—results of two phase 3 trials.
        N Engl J Med. 2014; 371: 326-338
        • Lebwohl M.
        • Strober B.
        • Menter A.
        • et al.
        Phase 3 studies comparing brodalumab with ustekinumab in psoriasis.
        N Engl J Med. 2015; 373: 1318-1328
        • Papp K.A.
        • Menter M.A.
        • Abe M.
        • et al.
        Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials.
        Br J Dermatol. 2015; 173: 949-961
        • Gordon K.B.
        • Blauvelt A.
        • Papp K.A.
        • et al.
        Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis.
        N Engl J Med. 2016; 375: 345-356
        • Reich K.
        • Papp K.A.
        • Blauvelt A.
        • et al.
        Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials.
        Lancet. 2017; 390: 276-288
        • Gottlieb A.B.
        • Blauvelt A.
        • Thaci D.
        • et al.
        Certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks from two phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2).
        J Am Acad Dermatol. 2018; 79: 302-314.e6
        • Bissonnette R.
        • Langley R.G.
        • Papp K.
        • et al.
        Humanized anti-CD2 monoclonal antibody treatment of plaque psoriasis: efficacy and pharmacodynamic results of two randomized, double-blind, placebo-controlled studies of intravenous and subcutaneous siplizumab.
        Arch Dermatol Res. 2009; 301: 429-442
        • Akcali C.
        • Guven E.H.
        • Kirtak N.
        • Inaloz H.S.
        • Ozgoztasi O.
        • Guvenc U.
        Serum concentrations of interleukin-2 and tumour necrosis factor-alpha under cyclosporine versus acitretin treatment in plaque-type psoriasis.
        J Int Med Res. 2014; 42: 1118-1122
        • Akhyani M.
        • Chams-Davatchi C.
        • Hemami M.R.
        • Fateh S.
        Efficacy and safety of mycophenolate mofetil vs. methotrexate for the treatment of chronic plaque psoriasis.
        J Eur Acad Dermatol Venereol. 2010; 24: 1447-1451
        • Ali M.E.
        • Rahman G.M.M.
        • Akhtar N.
        • Wahab M.A.
        • Rashid M.M.
        • Islam A.Z.M.M.
        Efficacy and safety of leflunomide in the treatment of plaque type psoriasis.
        J Pak Assoc Dermatol. 2009; 19: 18-22
        • Anil Kumar M.S.
        • Papp K.
        • Tainaka R.
        • et al.
        Randomized, controlled study of bleselumab (ASKP1240) pharmacokinetics and safety in patients with moderate-to-severe plaque psoriasis.
        Biopharm Drug Dispos. 2018; 39: 245-255
        • Asahina A.
        • Etoh T.
        • Igarashi A.
        • et al.
        Oral tofacitinib efficacy, safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: a randomized, double-blind, phase 3 study.
        J Dermatol. 2016; 43: 869-880
        • Asahina A.
        • Nakagawa H.
        • Etoh T.
        • Ohtsuki M.
        Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: efficacy and safety results from a phase II/III randomized controlled study.
        J Dermatol. 2010; 37: 299-310
        • Bachelez H.
        • van de Kerkhof P.C.
        • Strohal R.
        • et al.
        Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial.
        Lancet. 2015; 386: 552-561
        • Balak D.M.
        • van Doorn M.B.
        • Arbeit R.D.
        • et al.
        IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis.
        Clin Immunol. 2017; 174: 63-72
        • Barker J.
        • Hoffmann M.
        • Wozel G.
        • et al.
        Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1).
        Br J Dermatol. 2011; 165: 1109-1117
        • Beissert S.
        • Pauser S.
        • Sticherling M.
        • et al.
        A comparison of mycophenolate mofetil with ciclosporine for the treatment of chronic plaque-type psoriasis.
        Dermatology. 2009; 219: 126-132
        • Bhuiyan M.S.I.
        • Sikder A.
        • Rashid M.M.
        • Rabin F.
        Role of oral colchicine in plaque type psoriasis. A randomized clinical trial comparing with oral methotrexate.
        J Pak Assoc Dermatol. 2010; 20: 146-151
        • Bissonnette R.
        • Luchi M.
        • Fidelus-Gort R.
        • et al.
        A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral Janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis.
        J Dermatolog Treat. 2016; 27: 332-338
        • Bissonnette R.
        • Papp K.
        • Poulin Y.
        • et al.
        A randomized, multicenter, double-blind, placebo-controlled phase 2 trial of ISA247 in patients with chronic plaque psoriasis.
        J Am Acad Dermatol. 2006; 54: 472-478
        • Blauvelt A.
        • Ferris L.K.
        • Yamauchi P.S.
        • et al.
        Extension of ustekinumab maintenance dosing interval in moderate-to-severe psoriasis: results of a phase IIIb, randomized, double-blinded, active-controlled, multicentre study (PSTELLAR).
        Br J Dermatol. 2017; 177: 1552-1561
        • Blauvelt A.
        • Lacour J.P.
        • Fowler Jr., J.F.
        • et al.
        Phase 3 randomised study of the proposed biosimilar adalimumab GP2017 in psoriasis—impact of multiple switches.
        Br J Dermatol. 2018; 179: 623-631
        • Blauvelt A.
        • Papp K.A.
        • Griffiths C.E.
        • et al.
        Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial.
        J Am Acad Dermatol. 2017; 76: 405-417
        • Blauvelt A.
        • Prinz J.C.
        • Gottlieb A.B.
        • et al.
        Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE).
        Br J Dermatol. 2015; 172: 484-493
        • Cai L.
        • Gu J.
        • Zheng J.
        • et al.
        Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double-blind study.
        J Eur Acad Dermatol Venereol. 2017; 31: 89-95
        • Caproni M.
        • Antiga E.
        • Melani L.
        • Volpi W.
        • Del Bianco E.
        • Fabbri P.
        Serum levels of IL-17 and IL-22 are reduced by etanercept, but not by acitretin, in patients with psoriasis: a randomized controlled trial.
        J Clin Immunol. 2009; 29: 210-214
        • Chaidemenos G.C.
        • Mourellou O.
        • Avgoustinaki N.
        • Papakonstantinou M.
        • Karakatsanis G.
        • Katsambas A.
        Intermittent vs. continuous 1-year cyclosporin use in chronic plaque psoriasis.
        J Eur Acad Dermatol Venereol. 2007; 21: 1203-1208
        • Choi C.W.
        • Kim B.R.
        • Seo E.
        • Youn S.W.
        The objective Psoriasis Area and Severity Index: a randomized controlled pilot study comparing the effectiveness of ciclosporin and methotrexate.
        Br J Dermatol. 2017; 177: 1740-1741
        • Christophers E.
        Targeting T-cell subsets to achieve remission.
        J Eur Acad Dermatol Venereol. 2003; 17: 6-11
        • Chua S.H.H.
        • Tioleco G.M.S.
        • Dayrit C.A.F.
        • Mojica W.P.
        • Dofitas B.L.
        • Frez L.F.
        Atorvastatin as adjunctive therapy for chronic plaque type psoriasis versus betamethasone valerate alone: a randomized, double-blind, placebo-controlled trial.
        Indian J Dermatol Venereol Leprol. 2017; 83: 441-447
        • Colombo D.
        • Cassano N.
        • Altomare G.
        • Giannetti A.
        • Vena G.A.
        Psoriasis relapse evaluation with week-end cyclosporine A treatment: results of a randomized, double-blind, multicenter study.
        Int J Immunopathol Pharmacol. 2010; 23: 1143-1152
        • David M.
        • Akerman L.
        • Ziv M.
        • et al.
        Treatment of plaque-type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial.
        J Eur Acad Dermatol Venereol. 2012; 26: 361-367
        • David M.
        • Gospodinov D.K.
        • Gheorghe N.
        • et al.
        Treatment of plaque-type psoriasis with oral CF101: data from a phase II/III multicenter, randomized, controlled trial.
        J Drugs Dermatol. 2016; 15: 931-938
        • de Groot M.
        • Teunissen M.B.
        • Ortonne J.P.
        • et al.
        Expression of the chemokine receptor CCR5 in psoriasis and results of a randomized placebo controlled trial with a CCR5 inhibitor.
        Arch Dermatol Res. 2007; 299: 305-313
        • de Vries A.C.
        • Thio H.B.
        • de Kort W.J.
        • et al.
        A prospective randomized controlled trial comparing infliximab and etanercept in patients with moderate-to-severe chronic plaque-type psoriasis: the Psoriasis Infliximab vs. Etanercept Comparison Evaluation (PIECE) study.
        Br J Dermatol. 2017; 176: 624-633
        • Dogra S.
        • Jain A.
        • Kanwar A.J.
        Efficacy and safety of acitretin in three fixed doses of 25, 35 and 50 mg in adult patients with severe plaque type psoriasis: a randomized, double blind, parallel group, dose ranging study.
        J Eur Acad Dermatol Venereol. 2013; 27: e305-e311
        • Dogra S.
        • Krishna V.
        • Kanwar A.J.
        Efficacy and safety of systemic methotrexate in two fixed doses of 10 mg or 25 mg orally once weekly in adult patients with severe plaque-type psoriasis: a prospective, randomized, double-blind, dose-ranging study.
        Clin Exp Dermatol. 2012; 37: 729-734
        • Drateln C.
        • Mercado C.
        • Rodriguez M.N.
        • et al.
        Efficacy of pioglitazone versus methotrexate in the treatment of psoriasis moderate-severe.
        Med Cutan Ibero Lat Am. 2015; 43: 122-124
        • Dubertret L.
        • Sterry W.
        • Bos J.D.
        • et al.
        Clinical Experience Acquired With the Efalizumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial.
        Br J Dermatol. 2006; 155: 170-181
        • El-Darouti M.A.
        • Hegazy R.A.
        • Abdel Hay R.M.
        • Rashed L.A.
        Study of T helper (17) and T regulatory cells in psoriatic patients receiving live attenuated varicella vaccine therapy in a randomized controlled trial.
        Eur J Dermatol. 2014; 24: 464-469
        • El-Mofty M.
        • el-Darouti M.
        • Rasheed H.
        • et al.
        Sulfasalazine and pentoxifylline in psoriasis: a possible safe alternative.
        J Dermatolog Treat. 2011; 22: 31-37
        • Ezquerra G.M.
        • Regana M.S.
        • Millet P.U.
        Combination of acitretin and oral calcitriol for treatment of plaque-type psoriasis.
        Acta Derm Venereol. 2007; 87: 449-450
        • Faghihi T.
        • Radfar M.
        • Mehrabian Z.
        • Ehsani A.H.
        • Rezaei Hemami M.
        Atorvastatin for the treatment of plaque-type psoriasis.
        Pharmacotherapy. 2011; 31: 1045-1050
        • Fallah Arani S.
        • Neumann H.
        • Hop W.C.
        • Thio H.B.
        Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a multicentre prospective randomized controlled clinical trial.
        Br J Dermatol. 2011; 164: 855-861
        • Faurschou A.
        • Gyldenlove M.
        • Rohde U.
        • et al.
        Lack of effect of the glucagon-like peptide-1 receptor agonist liraglutide on psoriasis in glucose-tolerant patients—a randomized placebo-controlled trial.
        J Eur Acad Dermatol Venereol. 2015; 29: 555-559
        • Flytstrom I.
        • Stenberg B.
        • Svensson A.
        • Bergbrant I.M.
        Methotrexate vs. ciclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial.
        Br J Dermatol. 2008; 158: 116-121
        • Gisondi P.
        • Del Giglio M.
        • Cotena C.
        • Girolomoni G.
        Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24-week, randomized, controlled, investigator-blinded pilot trial.
        Br J Dermatol. 2008; 158: 1345-1349
        • Goldminz A.M.
        • Suarez-Farinas M.
        • Wang A.C.
        • Dumont N.
        • Krueger J.G.
        • Gottlieb A.B.
        CCL20 and IL22 messenger RNA expression after adalimumab vs methotrexate treatment of psoriasis: a randomized clinical trial.
        JAMA Dermatol. 2015; 151: 837-846
        • Gordon K.B.
        • Duffin K.C.
        • Bissonnette R.
        • et al.
        A phase 2 trial of guselkumab versus adalimumab for plaque psoriasis.
        N Engl J Med. 2015; 373: 136-144
        • Gordon K.B.
        • Langley R.G.
        • Gottlieb A.B.
        • et al.
        A phase III, randomized, controlled trial of the fully human IL-12/23 mAb briakinumab in moderate-to-severe psoriasis.
        J Invest Dermatol. 2012; 132: 304-314
        • Gordon K.B.
        • Langley R.G.
        • Leonardi C.
        • et al.
        Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study.
        J Am Acad Dermatol. 2006; 55: 598-606
        • Gordon K.B.
        • Papp K.A.
        • Hamilton T.K.
        • et al.
        Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial.
        JAMA. 2003; 290: 3073-3080
        • Gordon K.B.
        • Vaishnaw A.K.
        • O'Gorman J.
        • Haney J.
        • Menter A.
        Treatment of psoriasis with alefacept: correlation of clinical improvement with reductions of memory T-cell counts.
        Arch Dermatol. 2003; 139: 1563-1570
        • 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
        • Gottlieb A.B.
        • Griffiths C.E.
        • Ho V.C.
        • et al.
        Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial.
        Br J Dermatol. 2005; 152: 1219-1227
        • Gottlieb A.B.
        • Langley R.G.
        • Strober B.E.
        • et al.
        A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis.
        Br J Dermatol. 2012; 167: 649-657
        • Gottlieb A.B.
        • Leonardi C.
        • Kerdel F.
        • Mehlis S.
        • Olds M.
        • Williams D.A.
        Efficacy and safety of briakinumab vs. etanercept and placebo in patients with moderate to severe chronic plaque psoriasis.
        Br J Dermatol. 2011; 165: 652-660
        • Gottlieb A.B.
        • Matheson R.T.
        • Lowe N.
        • et al.
        A randomized trial of etanercept as monotherapy for psoriasis.
        Arch Dermatol. 2003; 139: 1627-1632
        • Gribetz C.H.
        • Blum R.
        • Brady C.
        • Cohen S.
        • Lebwohl M.
        An extended 16-week course of alefacept in the treatment of chronic plaque psoriasis.
        J Am Acad Dermatol. 2005; 53: 73-75
        • Griffiths C.E.
        • Strober B.E.
        • van de Kerkhof P.
        • et al.
        Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis.
        N Engl J Med. 2010; 362: 118-128
        • Griffiths C.E.M.
        • Thaci D.
        • Gerdes S.
        • et al.
        The EGALITY study: a confirmatory, randomized, double-blind study comparing the efficacy, safety and immunogenicity of GP2015, a proposed etanercept biosimilar, vs. the originator product in patients with moderate-to-severe chronic plaque-type psoriasis.
        Br J Dermatol. 2017; 176: 928-938
        • Hafez V.G.
        • Bosseila M.
        • Abdel Halim M.R.
        • Shaker O.G.
        • Kamal M.
        • Kareem H.S.
        Clinical effects of “pioglitazone”, an insulin sensitizing drug, on psoriasis vulgaris and its co-morbidities, a double blinded randomized controlled trialx1.
        J Dermatolog Treat. 2015; 26: 208-214
        • Heydendael V.M.
        • Spuls P.I.
        • Opmeer B.C.
        • et al.
        Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis.
        N Engl J Med. 2003; 349: 658-665
        • Igarashi A.
        • Kato T.
        • Kato M.
        • Song M.
        • Nakagawa H.
        Efficacy and safety of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis: long-term results from a phase 2/3 clinical trial.
        J Dermatol. 2012; 39: 242-252
        • Jin T.
        • Sun Z.
        • Chen X.
        • et al.
        Serum human beta-defensin-2 is a possible biomarker for monitoring response to JAK inhibitor in psoriasis patients.
        Dermatology. 2017; 233: 164-169
        • Khattri S.
        • Goldblum O.
        • Solotkin K.
        • et al.
        Early onset of clinical improvement with ixekizumab in a randomized, open-label study of patients with moderate-to-severe plaque psoriasis.
        J Clin Aesthet Dermatol. 2018; 11: 33-37
        • Kimball A.B.
        • Gordon K.B.
        • Langley R.G.
        • Menter A.
        • Chartash E.K.
        • Valdes J.
        Safety and efficacy of ABT-874, a fully human interleukin 12/23 monoclonal antibody, in the treatment of moderate to severe chronic plaque psoriasis: results of a randomized, placebo-controlled, phase 2 trial.
        Arch Dermatol. 2008; 144: 200-207
        • Krueger G.G.
        Clinical response to alefacept: results of a phase 3 study of intravenous administration of alefacept in patients with chronic plaque psoriasis.
        J Eur Acad Dermatol Venereol. 2003; 17: 17-24
        • Krueger G.G.
        • Langley R.G.
        • Leonardi C.
        • et al.
        A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis.
        N Engl J Med. 2007; 356: 580-592
        • Krueger J.
        • Clark J.D.
        • Suarez-Farinas M.
        • et al.
        Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: a randomized phase 2 study.
        J Allergy Clin Immunol. 2016; 137: 1079-1090
        • Krueger J.G.
        • Suarez-Farinas M.
        • Cueto I.
        • et al.
        A randomized, placebo-controlled study of SRT2104, a SIRT1 activator, in patients with moderate to severe psoriasis.
        PLoS One. 2015; 10: e0142081
        • Krupashankar D.S.
        • Dogra S.
        • Kura M.
        • et al.
        Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, phase-III study.
        J Am Acad Dermatol. 2014; 71: 484-492
        • Lajevardi V.
        • Hallaji Z.
        • Daklan S.
        • Abedini R.
        • Goodarzi A.
        • Abdolreza M.
        The efficacy of methotrexate plus pioglitazone vs. methotrexate alone in the management of patients with plaque-type psoriasis: a single-blinded randomized controlled trial.
        Int J Dermatol. 2015; 54: 95-101
        • Langley R.G.
        • Papp K.
        • Gooderham M.
        • et al.
        Efficacy and safety of continuous every-2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase III trial (IXORA-P).
        Br J Dermatol. 2018; 178: 1315-1323
        • Langley R.G.
        • Tsai T.F.
        • Flavin S.
        • et al.
        Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial.
        Br J Dermatol. 2018; 178: 114-123
        • Lebwohl M.
        • Blauvelt A.
        • Paul C.
        • et al.
        Certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placebo-controlled study (CIMPACT).
        J Am Acad Dermatol. 2018; 79: 266-276
        • Lebwohl M.
        • Tyring S.K.
        • Hamilton T.K.
        • et al.
        A novel targeted T-cell modulator, efalizumab, for plaque psoriasis.
        N Engl J Med. 2003; 349: 2004-2013
        • Lee J.H.
        • Youn J.I.
        • Kim T.Y.
        • et al.
        A multicenter, randomized, open-label pilot trial assessing the efficacy and safety of etanercept 50 mg twice weekly followed by etanercept 25 mg twice weekly, the combination of etanercept 25 mg twice weekly and acitretin, and acitretin alone in patients with moderate to severe psoriasis.
        BMC Dermatol. 2016; 16: 11
        • Leonardi C.
        • Matheson R.
        • Zachariae C.
        • et al.
        Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis.
        N Engl J Med. 2012; 366: 1190-1199
        • Leonardi C.L.
        • Kimball A.B.
        • Papp K.A.
        • et al.
        Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibodpsoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1).
        Lancet. 2008; 371: 1665-1674
        • Leonardi C.L.
        • Papp K.A.
        • Gordon K.B.
        • et al.
        Extended efalizumab therapy improves chronic plaque psoriasis: results from a randomized phase III trial.
        J Am Acad Dermatol. 2005; 52: 425-433
        • Leonardi C.L.
        • Powers J.L.
        • Matheson R.T.
        • et al.
        Etanercept as monotherapy in patients with psoriasis.
        N Engl J Med. 2003; 349: 2014-2022
        • Ludbrook V.J.
        • Hicks K.J.
        • Hanrott K.E.
        • et al.
        Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study.
        Br J Dermatol. 2016; 174: 985-995
        • Malik T.
        • Ejaz A.
        Comparison of methotrexate and azathioprine in the treatment of psoriasis: a randomized controlled trial.
        J Pak Assoc Dermatol. 2010; 20: 152-157
        • Menter A.
        • Feldman S.R.
        • Weinstein G.D.
        • et al.
        A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis.
        J Am Acad Dermatol. 2007; 56: 31.e1-31.e15
        • Menter A.
        • Gordon K.
        • Carey W.
        • et al.
        Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis.
        Arch Dermatol. 2005; 141: 31-38
        • 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
        • Micali G.
        • Wilsmann-Theis D.
        • Mallbris L.
        • et al.
        Etanercept reduces symptoms and severity of psoriasis after cessation of cyclosporine therapy: results of the SCORE study.
        Acta Derm Venereol. 2015; 95: 57-61
        • Mittal R.
        • Malhotra S.
        • Pandhi P.
        • Kaur I.
        • Dogra S.
        Efficacy and safety of combination Acitretin and Pioglitazone therapy in patients with moderate to severe chronic plaque-type psoriasis: a randomized, double-blind, placebo-controlled clinical trial.
        Arch Dermatol. 2009; 145: 387-393
        • Moore A.
        • Gordon K.
        • Kang S.
        • et al.
        A randomized, open-label trial of continuous versus interrupted etanercept therapy in the treatment of psoriasis.
        J Am Acad Dermatol. 2007; 56: 598-603
        • Mrowietz U.
        • Leonardi C.L.
        • Girolomoni G.
        • et al.
        Secukinumab retreatment-as-needed versus fixed-interval maintenance regimen for moderate to severe plaque psoriasis: a randomized, double-blind, noninferiority trial (SCULPTURE).
        J Am Acad Dermatol. 2015; 73: 27-36.e1
        • Mrowietz U.
        • Szepietowski J.C.
        • Loewe R.
        • et al.
        Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, Fumaderm®- and placebo-controlled trial (BRIDGE).
        Br J Dermatol. 2017; 176: 615-623
        • Nakagawa H.
        • Niiro H.
        • Ootaki K.
        Brodalumab, a human anti-interleukin-17-receptor antibody in the treatment of Japanese patients with moderate-to-severe plaque psoriasis: efficacy and safety results from a phase II randomized controlled study.
        J Dermatol Sci. 2016; 81: 44-52
        • Naseri M.
        • Hadipour A.
        • Sepaskhah M.
        • Namazi M.R.
        The remarkable beneficial effect of adding oral simvastatin to topical betamethasone for treatment of psoriasis: a double-blind, randomized, placebo-controlled study.
        Niger J Med. 2010; 19: 58-61
        • Netto E.M.
        • Takahashi D.
        • de Fatima Paim de Oliveira M.
        • et al.
        Phase II randomized, placebo-controlled trial of M. vaccae-derived protein (PVAC) for the treatment of psoriasis.
        Vaccine. 2006; 24: 5056-5063
        • Noor S.M.
        • Ayub N.
        • Paracha M.M.
        Efficacy and safety of methotrexate versus acitretin in chronic plaque psoriasis.
        J Postgrad Med Inst. 2017; 31: 4-7
        • Ohtsuki M.
        • Kubo H.
        • Morishima H.
        • Goto R.
        • Zheng R.
        • Nakagawa H.
        Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study.
        J Dermatol. 2018; 45: 1053-1062
        • Ohtsuki M.
        • Okubo Y.
        • Komine M.
        • et al.
        Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: efficacy, safety and tolerability results from a phase 2b randomized controlled trial.
        J Dermatol. 2017; 44: 873-884
        • Ortonne J.P.
        Clinical response to alefacept: results of a phase 3 study of intramuscular administration of alefacept in patients with chronic plaque psoriasis.
        J Eur Acad Dermatol Venereol. 2003; 17: 12-16
        • Papp K.
        • Bachelez H.
        • Costanzo A.
        • et al.
        Clinical similarity of biosimilar ABP 501 to adalimumab in the treatment of patients with moderate to severe plaque psoriasis: a randomized, double-blind, multicenter, phase III study.
        J Am Acad Dermatol. 2017; 76: 1093-1102
        • Papp K.
        • Bissonnette R.
        • Rosoph L.
        • et al.
        Efficacy of ISA247 in plaque psoriasis: a randomised, multicentre, double-blind, placebo-controlled phase III study.
        Lancet. 2008; 371: 1337-1342
        • Papp K.
        • Cather J.C.
        • Rosoph L.
        • et al.
        Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial.
        Lancet. 2012; 380: 738-746
        • Papp K.
        • Pariser D.
        • Catlin M.
        • et al.
        A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis.
        Br J Dermatol. 2015; 173: 767-776
        • Papp K.
        • Reich K.
        • Leonardi C.L.
        • et al.
        Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1).
        J Am Acad Dermatol. 2015; 73: 37-49
        • Papp K.
        • Thaci D.
        • Reich K.
        • et al.
        Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial.
        Br J Dermatol. 2015; 173: 930-939
        • Papp K.A.
        • Barber K.
        • Bissonnette R.
        • et al.
        A Randomized, blinded assessor study to Evaluate the efFIcacy and safety of etanercept 50 mg once weekly plus as Needed topical agent vs. Etanercept 50 mg twice weekly in patients with moderate to severe plaque psoriasis (REFINE).
        J Eur Acad Dermatol Venereol. 2015; 29: 361-366
        • Papp K.A.
        • Blauvelt A.
        • Bukhalo M.
        • et al.
        Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis.
        N Engl J Med. 2017; 376: 1551-1560
        • Papp K.A.
        • Bressinck R.
        • Fretzin S.
        • et al.
        Safety of efalizumab in adults with chronic moderate to severe plaque psoriasis: a phase IIIb, randomized, controlled trial.
        Int J Dermatol. 2006; 45: 605-614
        • Papp K.A.
        • Kaufmann R.
        • Thaci D.
        • Hu C.
        • Sutherland D.
        • Rohane P.
        Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison study.
        J Eur Acad Dermatol Venereol. 2013; 27: e376-e383
        • Papp K.A.
        • Langley R.G.
        • Lebwohl M.
        • et al.
        Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2).
        Lancet. 2008; 371: 1675-1684
        • Papp K.A.
        • Langley R.G.
        • Sigurgeirsson B.
        • et al.
        Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study.
        Br J Dermatol. 2013; 168: 412-421
        • Papp K.A.
        • Leonardi C.
        • Menter A.
        • et al.
        Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis.
        N Engl J Med. 2012; 366: 1181-1189
        • Papp K.A.
        • Menter A.
        • Strober B.
        • et al.
        Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a phase 2b randomized placebo-controlled dose-ranging study.
        Br J Dermatol. 2012; 167: 668-677
        • Papp K.A.
        • Menter M.A.
        • Raman M.
        • et al.
        A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis.
        Br J Dermatol. 2016; 174: 1266-1276
        • Papp K.A.
        • Reich K.
        • Paul C.
        • et al.
        A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis.
        Br J Dermatol. 2016; 175: 273-286
        • Paul C.
        • Cather J.
        • Gooderham M.
        • et al.
        Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2).
        Br J Dermatol. 2015; 173: 1387-1399
        • Paul C.
        • Lacour J.P.
        • Tedremets L.
        • et al.
        Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE).
        J Eur Acad Dermatol Venereol. 2015; 29: 1082-1090
        • Paul C.
        • Puig L.
        • Kragballe K.
        • et al.
        Transition to ustekinumab in patients with moderate-to-severe psoriasis and inadequate response to methotrexate: a randomized clinical trial (TRANSIT).
        Br J Dermatol. 2014; 170: 425-434
        • Radmanesh M.
        • Rafiei B.
        • Moosavi Z.B.
        • Sina N.
        Weekly vs. daily administration of oral methotrexate (MTX) for generalized plaque psoriasis: a randomized controlled clinical trial.
        Int J Dermatol. 2011; 50: 1291-1293
        • Reich K.
        • Armstrong A.W.
        • Foley P.
        • et al.
        Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial.
        J Am Acad Dermatol. 2017; 76: 418-431
        • Reich K.
        • Gooderham M.
        • Green L.
        • et al.
        The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE).
        J Eur Acad Dermatol Venereol. 2017; 31: 507-517
        • Reich K.
        • Langley R.G.
        • Papp K.A.
        • et al.
        A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis.
        N Engl J Med. 2011; 365: 1586-1596
        • Reich K.
        • Nestle F.O.
        • Papp K.
        • et al.
        Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial.
        Lancet. 2005; 366: 1367-1374
        • Reich K.
        • Ortonne J.P.
        • Gottlieb A.B.
        • et al.
        Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab' certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension.
        Br J Dermatol. 2012; 167: 180-190
        • Reich K.
        • Papp K.A.
        • Matheson R.T.
        • et al.
        Evidence that a neutrophil-keratinocyte crosstalk is an early target of IL-17A inhibition in psoriasis.
        Exp Dermatol. 2015; 24: 529-535
        • Reich K.
        • Pinter A.
        • Lacour J.P.
        • et al.
        Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study.
        Br J Dermatol. 2017; 177: 1014-1023
        • Rich P.
        • Sigurgeirsson B.
        • Thaci D.
        • et al.
        Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study.
        Br J Dermatol. 2013; 168: 402-411
        • Roberti M.L.
        • Ricottini L.
        • Capponi A.
        • et al.
        Immunomodulating treatment with low dose interleukin-4, interleukin-10 and interleukin-11 in psoriasis vulgaris.
        J Biol Regul Homeost Agents. 2014; 28: 133-139
        • Saurat J.H.
        • Stingl G.
        • Dubertret L.
        • et al.
        Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION).
        Br J Dermatol. 2008; 158: 558-566
        • Saxena V.N.
        • Dogra J.
        Long-term oral azithromycin in chronic plaque psoriasis: a controlled trial.
        Eur J Dermatol. 2010; 20: 329-333
        • Shafiq N.
        • Malhotra S.
        • Pandhi P.
        • Gupta M.
        • Kumar B.
        • Sandhu K.
        Pilot trial: pioglitazone versus placebo in patients with plaque psoriasis (the P6).
        Int J Dermatol. 2005; 44: 328-333
        • Shintani Y.
        • Kaneko N.
        • Furuhashi T.
        • Saito C.
        • Morita A.
        Safety and efficacy of a fixed-dose cyclosporin microemulsion (100 mg) for the treatment of psoriasis.
        J Dermatol. 2011; 38: 966-972
        • Singh S.K.
        • Rai T.
        Relapse in psoriasis with two different tapering regimens of methotrexate: a randomized open-label controlled study.
        Indian J Dermatol Venereol Leprol. 2015; 81: 144-147
        • Skov L.
        • Kragballe K.
        • Zachariae C.
        • et al.
        HuMax-CD4: a fully human monoclonal anti-CD4 antibody for the treatment of psoriasis vulgaris.
        Arch Dermatol. 2003; 139: 1433-1439
        • Sticherling M.
        • Mrowietz U.
        • Augustin M.
        • et al.
        Secukinumab is superior to fumaric acid esters in treating patients with moderate-to-severe plaque psoriasis who are naive to systemic treatments: results from the randomized controlled PRIME trial.
        Br J Dermatol. 2017; 177: 1024-1032
        • Strober B.E.
        • Crowley J.J.
        • Yamauchi P.S.
        • Olds M.
        • Williams D.A.
        Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis.
        Br J Dermatol. 2011; 165: 661-668
        • Strohal R.
        • Puig L.
        • Chouela E.
        • et al.
        The efficacy and safety of etanercept when used with as-needed adjunctive topical therapy in a randomised, double-blind study in subjects with moderate-to-severe psoriasis (the PRISTINE trial).
        J Dermatolog Treat. 2013; 24: 169-178
        • Thaci D.
        • Blauvelt A.
        • Reich K.
        • et al.
        Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial.
        J Am Acad Dermatol. 2015; 73: 400-409
        • Torii H.
        • Nakagawa H.
        Infliximab monotherapy in Japanese patients with moderate-to-severe plaque psoriasis and psoriatic arthritis. A randomized, double-blind, placebo-controlled multicenter trial.
        J Dermatol Sci. 2010; 59: 40-49
        • Tsai T.F.
        • Ho J.C.
        • Song M.
        • et al.
        Efficacy and safety of ustekinumab for the treatment of moderate-to-severe psoriasis: a phase III, randomized, placebo-controlled trial in Taiwanese and Korean patients (PEARL).
        J Dermatol Sci. 2011; 63: 154-163
        • Tyring S.
        • Gottlieb A.
        • Papp K.
        • et al.
        Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial.
        Lancet. 2006; 367: 29-35
        • Vaclavkova A.
        • Chimenti S.
        • Arenberger P.
        • et al.
        Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial.
        Lancet. 2014; 384: 2036-2045
        • van Bezooijen J.S.
        • Balak D.M.
        • van Doorn M.B.
        • et al.
        Combination therapy of etanercept and fumarates versus etanercept monotherapy in psoriasis: a randomized exploratory study.
        Dermatology. 2016; 232: 407-414
        • van de Kerkhof P.C.
        • Segaert S.
        • Lahfa M.
        • et al.
        Once weekly administration of etanercept 50 mg is efficacious and well tolerated in patients with moderate-to-severe plaque psoriasis: a randomized controlled trial with open-label extension.
        Br J Dermatol. 2008; 159: 1177-1185
        • Vena G.A.
        • Cassano N.
        • Galluccio A.
        • et al.
        Evaluation of the efficacy and tolerability of a new intermittent treatment regimen with cyclosporin A in severe psoriasis.
        G Ital Dermatol Venereol. 2005; 140: 575-582
        • Warren R.B.
        • Mrowietz U.
        • von Kiedrowski R.
        • et al.
        An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
        Lancet. 2017; 389: 528-537
        • Williams B.
        • Vanags D.
        • Hall S.
        • et al.
        Efficacy and safety of chaperonin 10 in patients with moderate to severe plaque psoriasis: evidence of utility beyond a single indication.
        Arch Dermatol. 2008; 144: 683-685
        • Wu W.Z.
        • Zhang F.R.
        Glycyrrhizin combined with acitretin improve clinical symptom of psoriasis via reducing Th17 cell differentiation and related serum cytokine concentrations.
        Int J Clin Exp Med. 2015; 8: 16266-16272
        • Yang H.Z.
        • Wang K.
        • Jin H.Z.
        • et al.
        Infliximab monotherapy for Chinese patients with moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled multicenter trial.
        Chin Med J (Engl). 2012; 125: 1845-1851
        • Yoon H.S.
        • Youn J.I.
        A comparison of two cyclosporine dosage regimens for the treatment of severe psoriasis.
        J Dermatolog Treat. 2007; 18: 286-290
        • Zachariae C.
        • Mork N.J.
        • Reunala T.
        • et al.
        The combination of etanercept and methotrexate increases the effectiveness of treatment in active psoriasis despite inadequate effect of methotrexate therapy.
        Acta Derm Venereol. 2008; 88: 495-501
        • Zhang J.
        • Tsai T.F.
        • Lee M.G.
        • et al.
        The efficacy and safety of tofacitinib in Asian patients with moderate to severe chronic plaque psoriasis: a phase 3, randomized, double-blind, placebo-controlled study.
        J Dermatol Sci. 2017; 88: 36-45
      2. Lee JH, Lee SH, Han K , Kim M. Alzheimer's disease risk in patients with psoriasis: a nationwide population-based cohort study [abstract P034]. Abstract presented at: 6th Congress of the Skin Inflammatory and Psoriasis International Network (SPIN). April 25-27, 2019; Paris, France.