Efficacy, Safety, and Immunogenicity of Biosimilar Adalimumab Advixa® Compared With Reference Product Humira® in Patients With Rheumatoid Arthritis in Bangladesh.

aimThis study evaluated the efficacy, safety, and immunogenicity of biosimilar adalimumab drug Advixa® (Incepta Pharmaceuticals Ltd, Dhaka, Bangladesh) in patients with moderate to severe rheumatoid arthritis (RA) compared to the reference drug Humira® (AbbVie Inc., North Chicago, IL, USA).

methodsIn this randomized, double-blind, prospective, parallel-group, active-controlled, non-inferiority trial, each of 144 patients was treated with six doses of Advixa® biweekly for up to 12 weeks. In the test group, there were 108 patients, and in the reference group, there were 36 patients. The primary endpoint was the proportion of the patients achieving the American College of Rheumatology 20% improvement criteria (ACR20) in response to the treatment. In contrast, ACR50, ACR70, and Disease Activity Score in 28 joints (DAS28) response were the secondary endpoints. The safety measurements included monitoring adverse events (AEs), serious AEs (SAEs), well-being assessment, and clinical laboratory abnormalities. Additionally, the level of anti-adalimumab antibody was assessed as a measure of immunogenicity against the drug.

resultsAfter 12 weeks, the per-protocol (PP) population treated every other week with Advixa® had statistically similar response rates as compared to Humira®: ACR20 erythrocyte sedimentation rate (ESR) (78.22% vs. 73.53%; P > 0.6), ACR50 ESR (55.45% vs. 52.94%; P > 0.8), ACR70 ESR (29.70% vs. 26.47%; P > 0.8). According to the intention to treat (ITT) population, the response rates were ACR20 (73% vs. 69%; P > 0.6), ACR50 (52% vs. 50%; P > 0.8), and ACR70 (28% vs. 25%; P > 0.8). In every criterion, the response rate for Advixa® was higher than Humira®. Similarly, the changes in DAS28-C-reactive protein (CRP) scores were -2.13 ± 1.43 vs -2.34 ± 1.55 in the PP population group (P > 0.4) and -2 ± 1.39 and -2 ± 1.56 in the ITT population group (P > 0.4) for Advixa® and Humira®, respectively. Six SAEs and 105 non-serious AEs were reported during the study. No significant difference was found between treatment groups for the incidence of SAEs (P > 0.3) and AEs (P > 0.7). There was no significant difference in the absolute value of change of anti-adalimumab antibody titer in the treatment groups from baseline to week 12 (P > 0.2).

conclusionsThe comprehensive assessment of efficacy, safety, and immunogenicity establishes the non-inferiority of Advixa® to Humira® at a 95% confidence level.