BACKGROUND: MSB11022 is a proposed adalimumab biosimilar. OBJECTIVES: To compare the efficacy, safety and immunogenicity of MSB11022 with reference adalimumab. METHODS: AURIEL-PsO was a double-blind randomized controlled equivalence trial, in which patients with moderate-to-severe chronic plaque-type psoriasis were randomized 1 : 1 to MSB11022 or reference adalimumab. The primary end point was ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 16, with a prespecified equivalence interval of ± 18%. Patients with a ≥50% improvement in PASI at week 16 were eligible to enter a double-blind extension period: patients receiving MSB11022 continued treatment, and patients receiving reference adalimumab were rerandomized 1 : 1 either to continue reference adalimumab or to switch to MSB11022. Other efficacy end points and safety, immunogenicity and pharmacokinetic parameters were evaluated at scheduled visits up to weeks 52 (efficacy and immunogenicity), 54 and 66 (safety). RESULTS: In total, 443 patients were randomized. The difference in PASI 75 response rates at week 16 between the treatment arms was -1·9%, and the 95% confidence interval (-7·8% to 4·1%) was within the prespecified equivalence interval. No notable difference in the incidence of treatment-emergent adverse events was observed between treatment arms up to the end of the trial, and no new safety signals were observed. Following treatment switch at week 16, no clinically meaningful differences in safety or immunogenicity were seen between treatment arms through to the end of the observation period. CONCLUSIONS: Therapeutic equivalence between MSB11022 and reference adalimumab was demonstrated. AURIEL-PsO provides evidence to support the similarity of both products with regard to efficacy, safety and immunogenicity. What's already known about this topic? Adalimumab is a fully human antitumour necrosis factor-α monoclonal antibody, indicated for the treatment of multiple inflammatory disorders, including psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel diseases and ankylosing spondylitis. MSB11022 is a proposed adalimumab biosimilar that has shown structural and functional similarity to the reference product in an extensive analytical comparability exercise. MSB11022 has demonstrated bioequivalence and comparable safety and immunogenicity profiles in a phase I study in healthy volunteers. What does this study add? This phase III study confirmed equivalent efficacy for MSB11022 and reference adalimumab in patients without any immunomodulation comedication in moderate-to-severe chronic plaque-type psoriasis at week 16. The efficacy, safety and immunogenicity of MSB11022 and reference adalimumab were similar over the respective observation periods (week 52 for efficacy and immunogenicity, week 66 for safety). A switch from reference adalimumab to MSB11022 at week 16 did not impact efficacy, safety or immunogenicity.

Cytel Geneva Switzerland

Dermatology Department 2nd Medical Faculty Charles University and Na Bulovce Hospital Prague Czech Republic

Fresenius Kabi Eysin Switzerland

K Papp Clinical Research and Probity Medical Research Inc Waterloo ON Canada

NIHR Clinical Research Facility University of Southampton Southampton U K

Br J Dermatol. 2020 Feb;182(2):266. doi: 10.1111/bjd.18717. PubMed

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Feldmann M, Maini RN. Anti‐TNF therapy, from rationale to standard of care: what lessons has it taught us? J Immunol 2010; 185:791–4. PubMed

Kaymakcalan Z, Sakorafas P, Bose S et al Comparisons of affinities, avidities, and complement activation of adalimumab, infliximab, and etanercept in binding to soluble and membrane tumor necrosis factor. Clin Immunol 2009; 131:308–16. PubMed

Lapadula G, Marchesoni A, Armuzzi A et al Adalimumab in the treatment of immune‐mediated diseases. Int J Immunopathol Pharmacol 2014; 27:33–48. PubMed

Putrik P, Ramiro S, Kvien TK et al Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth? Ann Rheum Dis 2014; 73:2010–21. PubMed

Kalo Z, Voko Z, Ostor A et al Patient access to reimbursed biological disease‐modifying antirheumatic drugs in the European region. J Mark Access Health Policy 2017; 5:1345580. PubMed PMC

Carrascosa JM, Jacobs I, Petersel D et al Biosimilar drugs for psoriasis: principles, present, and near future. Dermatol Ther (Heidelb) 2018; 8:173–94. PubMed PMC

Blauvelt A, Cohen AD, Puig L et al Biosimilars for psoriasis: preclinical analytical assessment to determine similarity. Br J Dermatol 2016; 174:282–6. PubMed

Blauvelt A, Puig L, Chimenti S et al Biosimilars for psoriasis: clinical studies to determine similarity. Br J Dermatol 2017; 177:23–33. PubMed

Cohen AD, Wu JJ, Puig L et al Biosimilars for psoriasis: worldwide overview of regulatory guidelines, uptake and implications for dermatology clinical practice. Br J Dermatol 2017; 177:1495–502. PubMed

Cohen HP, Blauvelt A, Rifkin RM et al Switching reference medicines to biosimilars: a systematic literature review of clinical outcomes. Drugs 2018; 78:463–78. PubMed PMC

European Medicines Agency . Guideline on similar biological medicinal products containing biotechnology‐derived proteins as active substance: non‐clinical and clinical issues. Available at: https://www.ema.europa.eu/documents/scientific-guideline/guideline-similar-biological-medicinal-products-containing-biotechnology-derived-proteins-active_en-2.pdf (last accessed 18 July 2019).

Magnenat L, Palmese A, Fremaux C et al Demonstration of physicochemical and functional similarity between the proposed biosimilar adalimumab MSB11022 and Humira. MAbs 2017; 9:127–39. PubMed PMC

Hyland E, Mant T, Vlachos P et al Comparison of the pharmacokinetics, safety, and immunogenicity of MSB11022, a biosimilar of adalimumab, with Humira® in healthy subjects. Br J Clin Pharmacol 2016; 82:983–93. PubMed PMC

Menter A, Tyring SK, Gordon K et al Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol 2008; 58:106–15. PubMed

Saurat JH, 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; 158:558–66. PubMed

Fredriksson T, Pettersson U. Severe psoriasis – oral therapy with a new retinoid. Dermatologica 1978; 157:238–44. PubMed

Schmitt J, Wozel G. The Psoriasis Area and Severity Index is the adequate criterion to define severity in chronic plaque‐type psoriasis. Dermatology 2005; 210:194–9. PubMed

Langley RG, Feldman SR, Nyirady J et al The 5‐point Investigator's Global Assessment (IGA) scale: a modified tool for evaluating plaque psoriasis severity in clinical trials. J Dermatolog Treat 2015; 26:23–31. PubMed

Piaggio G, Elbourne DR, Pocock SJ et al Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA 2012; 308:2594–604. PubMed

Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) – a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19:210–16. PubMed

Yfantopoulos J, Chantzaras A, Kontodimas S. Assessment of the psychometric properties of the EQ‐5D‐3L and EQ‐5D‐5L instruments in psoriasis. Arch Dermatol Res 2017; 309:357–70. PubMed

Bruce B, Fries JF. The Health Assessment Questionnaire (HAQ). Clin Exp Rheumatol 2005; 23 (5 Suppl. 39):S14–18. PubMed

Cauli A, Gladman DD, Mathieu A et al Patient global assessment in psoriatic arthritis: a multicenter GRAPPA and OMERACT study. J Rheumatol 2011; 38:898–903. PubMed

Mrowietz U, Kragballe K, Reich K et al An assessment of adalimumab efficacy in three phase III clinical trials using the European Consensus Programme criteria for psoriasis treatment goals. Br J Dermatol 2013; 168:374–80. PubMed

Van Lumig PP, Lecluse LL, Driessen RJ et al Switching from etanercept to adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure, secondary failure or intolerance to etanercept. Br J Dermatol 2010; 163:838–46. PubMed

Woolf RT, Smith CH, Robertson K et al Switching to adalimumab in patients with moderate to severe psoriasis who have failed on etanercept: a retrospective case cohort study. Br J Dermatol 2010; 163:889–92. PubMed

Bissonnette R, Bolduc C, Poulin Y et al Efficacy and safety of adalimumab in patients with plaque psoriasis who have shown an unsatisfactory response to etanercept. J Am Acad Dermatol 2010; 63:228–34. PubMed

Pitarch G, Sanchez‐Carazo JL, Mahiques L et al Treatment of psoriasis with adalimumab. Clin Exp Dermatol 2007; 32:18–22. PubMed

Ryan C, Kirby B, Collins P et al Adalimumab treatment for severe recalcitrant chronic plaque psoriasis. Clin Exp Dermatol 2009; 34:784–8. PubMed

Menter A, Gordon KB, Leonardi CL et al Efficacy and safety of adalimumab across subgroups of patients with moderate to severe psoriasis. J Am Acad Dermatol 2010; 63:448–56. PubMed

Prussick R, Unnebrink K, Valdecantos WC. Efficacy of adalimumab compared with methotrexate or placebo stratified by baseline BMI in a randomized placebo‐controlled trial in patients with psoriasis. J Drugs Dermatol 2015; 14:864–8. PubMed

Thaçi D, Ortonne JP, Chimenti S et al A phase IIIb, multicentre, randomized, double‐blind, vehicle‐controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study. Br J Dermatol 2010; 163:402–11. PubMed

Wu JJ. Contemporary management of moderate to severe plaque psoriasis. Am J Manag Care 2017; 23 (21 Suppl.):S403–16. PubMed

Asahina A, Nakagawa H, Etoh T et al 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. PubMed

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. PubMed PMC

Papp K, Bachelez H, Costanzo A et al Clinical similarity of the biosimilar ABP 501 compared with adalimumab after single transition: long‐term results from a randomized controlled, double‐blind, 52‐week, phase III trial in patients with moderate‐to‐severe plaque psoriasis. Br J Dermatol 2017; 177:1562–74. PubMed

Lafuente‐Urrez RF, Perez‐Pelegay J. Impact of obesity on the effectiveness of adalimumab for the treatment of psoriasis: a retrospective study of 30 patients in daily practice. Eur J Dermatol 2014; 24:217–23. PubMed

Gordon KB, Duffin KC, Bissonnette R et al A phase 2 trial of guselkumab versus adalimumab for plaque psoriasis. N Engl J Med 2015; 373:136–44. PubMed

Gordon KB, Langley RG, 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. PubMed

AbbVie Inc . Prescribing information: HUMIRA (adalimumab) injection, for subcutaneous use. Available at: http://www.rxabbvie.com/pdf/humira.pdf (last accessed 18 July 2019).

Song S, Yang L, Trepicchio WL et al Understanding the supersensitive anti‐drug antibody assay: unexpected high anti‐drug antibody incidence and its clinical relevance. J Immunol Res 2016; 2016:3072586. PubMed PMC

Gorovits B, Baltrukonis DJ, Bhattacharya I et al Immunoassay methods used in clinical studies for the detection of anti‐drug antibodies to adalimumab and infliximab. Clin Exp Immunol 2018; 192:348–65. PubMed PMC

Menting SP, Coussens E, Pouw MF et al Developing a therapeutic range of adalimumab serum concentrations in management of psoriasis: a step toward personalized treatment. JAMA Dermatol 2015; 151:616–22. PubMed

Blauvelt A, Lacour JP, Fowler JF Jr et al Phase III randomized study of the proposed biosimilar adalimumab GP2017 in psoriasis: impact of multiple switches. Br J Dermatol 2018; 179:623–31. PubMed

Jorgensen KK, Olsen IC, Goll GL et al Switching from originator infliximab to biosimilar CT‐P13 compared with maintained treatment with originator infliximab (NOR‐SWITCH): a 52‐week, randomised, double‐blind, non‐inferiority trial. Lancet 2017; 389:2304–16. PubMed

Weinblatt ME, Baranauskaite A, Dokoupilova E et al Switching from reference adalimumab to SB5 (adalimumab biosimilar) in patients with rheumatoid arthritis: fifty‐two‐week phase III randomized study results. Arthritis Rheumatol 2018; 70:832–40. PubMed PMC

Yoo DH, Prodanovic N, Jaworski J et al Efficacy and safety of CT‐P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT‐P13 and continuing CT‐P13 in the PLANETRA extension study. Ann Rheum Dis 2017; 76:355–63. PubMed PMC