Objectives To compare the safety, efficacy, and immunogenicity of MSB11022 (acetate-buffered formulation), an adalimumab biosimilar, with the reference product. Method AURIEL-RA study was a phase 3, multicenter, randomized, double-blind, parallel group trial (NCT03052322). Patients with moderately-to-severely active rheumatoid arthritis (RA) with an inadequate response to methotrexate were randomized 1:1 to MSB11022 or reference adalimumab. The primary endpoint was the incidence of treatment-emergent adverse events of special interest (AESIs) (predefined as hypersensitivity) up to week 52. The key secondary endpoint was ACR20 (≥ 20% improvement in American College of Rheumatology core set measurements from baseline) at week 12. Other efficacy endpoints, quality of life, immunogenicity, and pharmacokinetic parameters were evaluated up to week 52. Secondary safety endpoints were evaluated up to week 52 and at a 4-month safety follow-up. Results In total, 288 patients were randomized. The proportion of patients experiencing ≥ 1 treatment-emergent AESI up to week 52 was similar between trial arms: 6 patients (4.2%; 95% CI 1.56, 8.91) receiving MSB11022, and 8 patients (5.5%; 95% CI 2.41, 10.58) receiving reference adalimumab. No clinically meaningful differences in efficacy, quality of life, or immunogenicity were seen between treatment arms up to week 52. No notable difference in the incidence of treatment-emergent adverse events was observed between treatment arms up to the end of the follow-up period. Conclusions These results suggest MSB11022 and reference adalimumab are similar in patients with moderately-to-severely active rheumatoid arthritis in terms of safety, immunogenicity, and efficacy. AURIEL-RA provides evidence to support the similarity of MSB11022 and adalimumab. Key Points• Incidences of hypersensitivity events were similar for MSB11022 (modified buffer) and reference adalimumab.• There was no difference in local reactions between MSB11022 (modified buffer) and reference adalimumab.• AURIEL-RA confirms the equivalence in efficacy and immunogenicity of MSB11022 (modified buffer) and reference adalimumab.

Summary 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.

Response based on PASI 75 did not statistically differ between either guselkumab or risankizumab and the anti-IL-17 agents. Similar findings were observed for PASI 50 and 90 outcomes. Conclusions: Based on clinical trial findings, guselkumab and risankizumab provide clinical benefit similar to that of anti-IL-17 agents and may provide incremental benefits in comparison to tildrakizumab, anti-TNF-a agents, ustekinumab, and apremilast.

Background:Adalimumab is a fully human anti-TNF mAb, indicated for the treatment of multiple inflammatory disorders. MSB11022 is a proposed adalimumab biosimilar that has shown analytical similarity [1] and bioequivalence to US-licensed and EU-approved adalimumab originator, as well as comparable safety, tolerability and immunogenicity in a phase I trial [2].Objectives:The aims of this multicentre, double-blind, parallel-group, 52-week phase III study (AURIEL-PsO, NCT02660580) were to demonstrate equivalence in efficacy (Psoriasis Area and Severity Index [PASI] 75) and to compare the safety and immunogenicity of MSB11022 vs. adalimumab originator in patients with moderate-to-severe chronic plaque psoriasis. This study was designed in-line with the biosimilar regulatory framework as part of the totality of evidence to confirm similarity and rationale for extrapolation.Methods:A total of 443 eligible patients (391 evaluable, including 43 with psoriatic arthritis) from 69 sites in 12 countries were randomised 1:1 and treated with MSB11022 (n=202) or adalimumab originator (n=189) (80 mg subcutaneously [SC] on day 1; 40 mg SC every other week from weeks 2−14). The primary endpoint was PASI 75 at week 16; equivalence was established if the 95% confidence interval (CI) for the treatment difference was within ±18%. Secondary endpoints included % change from baseline in PASI (equivalence confirmed if 95% CI within ±15%), Physician Global Assessment (PGA), quality of life (QoL), immunogenicity and safety. Interim results at week 16 are presented.Results:Patient baseline characteristics were comparable between MSB11022 and adalimumab originator groups: mean age 44.8 vs. 42.4 years, male 66.8% vs. 68.3%, mean PASI score 20.7 vs. 21.2, respectively. PASI 75 scores were 89.6% for MSB11022 and 91.5% for adalimumab originator (difference −1.9% [95% CI −7.82–4.16]). Mean % change from baseline in PASI was −90.6% for MSB11022 and −91.7% for adalimumab originator (difference −1.0% [95% CI −1.23–2.98]). PGA and QoL scores were comparable between treatment groups. The incidence of treatment-emergent adverse events (TEAEs)/serious TEAEs was 51.1/3.6% for MSB11022 and 53.2/2.7% for adalimumab originator. Immunogenicity profiles of MSB11022 and adalimumab originator were also similar and consistent.Conclusions:Week 16 results of this phase III confirmatory study demonstrated equivalent efficacy and similar safety and immunogenicity profiles for MSB11022 vs. adalimumab originator at 16 weeks in patients with moderate-to-severe chronic psoriasis.References[1] Magnenat L, et al. Demonstration of physicochemical and functional similarity between the proposed biosimilar adalimumab MSB11022 and Humira®. MAbs. 2017;9:127–139.[2] Hyland E, 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.Disclosure of Interest:J. Hercogová Grant/research support from: Fresenius Kabi, Consultant for: Fresenius Kabi, K. Papp Grant/res...