A prospective, randomized, double-blind, multicentre, parallel-group, active controlled study to compare efficacy and safety of biosimilar adalimumab (Exemptia; ZRC-3197) and adalimumab (Humira) in patients with rheumatoid arthritis.

In this study, efficacy, tolerability and safety of biosimilar adalimumab (Exemptia; Zydus Cadila) was compared with reference adalimumab (Humira; AbbVie) in patients with moderate to severe rheumatoid arthritis (RA). In this multicentre, prospective, randomized, double-blind, active controlled parallel arm study, 120 patients with moderate to severe RA were given 40 mg of either test adalimumab (Exemptia) or reference adalimumab (Humira) by subcutaneous route every other week for 12 weeks. The primary endpoint was proportion of responders in two tretament groups by American College of Rheumatology 20 (ACR20) at week 12. The secondary endpoints were change in Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP) and proportion of patients with an ACR50 and ACR70 response in two treatment groups at week 12. Safety outcomes were also assessed. After 12 weeks, patients treated every other week with test adalimumab (Zydus Cadila) had statistically similar response rates as compared to reference adalimumab (AbbVie): ACR20 (82% vs. 79.2%; P > 0.7); ACR50 (46%, vs. 43.4%; P > 0.7); ACR70 (14% vs. 15.1%; P > 0.8). The change in DAS28-CRP score was -2.1 ± 1.09 and -2.1 ± 1.21, in test and reference products, respectively. It was statistically significant compared to baseline, but not significantly different between the two products. Three serious adverse events and no death was reported during the study. Both adalimumab preparations were safe and well tolerated in this study. The results demonstrated biosimilarity with respect to efficacy, tolerability and safety of test adalimumab (Exemptia) and reference adalimumab (Humira) in patients with moderate to severe RA.

Jani RH ，Gupta R ，Bhatia G ，Rathi G ，Ashok Kumar P ，Sharma R ，Kumar U ，Gauri LA ，Jadhav P ，Bartakke G ，Haridas V ，Jain D ，Mendiratta SK ... -  《-》

Similar efficacy, safety and immunogenicity of adalimumab biosimilar BI 695501 and Humira reference product in patients with moderately to severely active rheumatoid arthritis: results from the phase III randomised VOLTAIRE-RA equivalence study.

To demonstrate clinical equivalence of adalimumab biosimilar candidate BI 695501 with Humira. Patients with active rheumatoid arthritis on stable methotrexate were randomised to BI 695501 or Humira in a double-blind, parallel-group, equivalence study. At week 24, patients were rerandomised to continue BI 695501 or Humira, or switch from Humira to BI 695501. The coprimary endpoints were the percentage of patients achieving the American College of Rheumatology 20% response criteria (ACR20) at weeks 12 and 24. Further efficacy and safety endpoints and immunogenicity were assessed up to week 58. 645 patients were randomised. At week 12, 67.0% and 61.1% (90% CI -0.9 to 12.7) of patients receiving BI 695501 (n=324) and Humira (n=321), respectively, achieved ACR20; at week 24 the corresponding values were 69.0% and 64.5% (95% CI -3.4 to 12.5). These differences were within prespecified margins (week 12: 90% CI (-12% to 15%); week 24: 95% CI (-15% to 15%)), demonstrating therapeutic bioequivalence. 593 patients were rerandomised at week 24. Up to week 48, mean change from baseline in Disease Activity Score 28-erythrocyte sedimentation rate and ACR20/ACR50/ACR70 response rates were similar across the switched (n=147), continuous BI 695501 (n=298) and continuous Humira (n=148) groups. Similar immunogenicity (antidrug antibodies (ADAs), ADA titres and neutralising antibodies) was seen between BI 695501 and Humira (to week 24) and across rerandomised groups (to week 48). Safety and tolerability profiles were similar between groups. BI 695501 demonstrated similar efficacy, safety and immunogenicity to Humira; switch from Humira to BI 695501 had no impact on efficacy, safety and immunogenicity. NCT02137226, Results.

Cohen SB ，Alonso-Ruiz A ，Klimiuk PA ，Lee EC ，Peter N ，Sonderegger I ，Assudani D ... -  《-》

A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inferiority clinical trial to compare efficacy and safety of biosimilar adalimumab (CinnoRA®) to the reference product (Humira®) in patients with active rheumatoid arth

Jamshidi A ，Gharibdoost F ，Vojdanian M ，Soroosh SG ，Soroush M ，Ahmadzadeh A ，Nazarinia MA ，Mousavi M ，Karimzadeh H ，Shakibi MR ，Rezaieyazdi Z ，Sahebari M ，Hajiabbasi A ，Ebrahimi AA ，Mahjourian N ，Rashti AM ... -  《-》

Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study.

ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab. In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity. A total of 526 patients were randomised (n=264, ABP 501; n=262 adalimumab) and 494 completed the study. ACR20 response at week 24 was 74.6% (ABP 501) and 72.4% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies. Results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA. NCT01970475; Results.

Cohen S ，Genovese MC ，Choy E ，Perez-Ruiz F ，Matsumoto A ，Pavelka K ，Pablos JL ，Rizzo W ，Hrycaj P ，Zhang N ，Shergy W ，Kaur P ... -  《-》

A comparative clinical study of PF-06410293, a candidate adalimumab biosimilar, and adalimumab reference product (Humira®) in the treatment of active rheumatoid arthritis.

Fleischmann RM ，Alten R ，Pileckyte M ，Lobello K ，Hua SY ，Cronenberger C ，Alvarez D ，Bock AE ，Sewell KL ... -  《-》