Similar Safety, Immunogenicity With Adalimumab Biosimilar and Reference Product in RA

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The study compared levels of efficacy, serum drug concentrations, immunogenicity, and safety of adalimumab biosimilar FKB327 with the reference product in patients with moderate to severe rheumatoid arthritis.

Adalimumab biosimilar FKB327 was equivalent to its reference product in terms of clinical efficacy and tolerability among patients with moderate to severe rheumatoid arthritis (RA), according to study results published in Arthritis Research & Therapy.

Investigators conducted a multicenter, phase 3, double-blind, randomized clinical trial of FKB327 against an adalimumab reference product (RP). FKB327 contains adalimumab, but with excipients different to those in RP, all of which are commonly used in the biologic treatment of RA.

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Patients aged ≥18 years with active RA according to the 2010 revised American College of Rheumatology (ACR) criteria were included in the study. Patients who had received prior treatment with the RP or any adalimumab-containing biosimilar were excluded from the study. In period 1 ( Identifier: NCT02260791) of the study, patients were randomly assigned 1:1 to receive either 40 mg subcutaneous FKB327 or 40 mg subcutaneous RP every other week for 22 weeks. The primary end point of period 1 was 20% improvement in ACR score (ACR20 response) by week 24. As secondary end points, investigators also assessed serum drug concentration levels, Disease Activity Score 28 for RA with C-reactive protein (DAS28-CRP), and ACR20, ACR50, and ACR70 response rates over time. Patients who completed period 1 were offered to enter period 2, a 30-week open-label extension study ( Identifier: NCT02405780). Patients who elected to enter period 2 were randomly assigned such that two-thirds remained on the same initial drug condition, providing 54 weeks of continuous treatment with either FKB327 or RP. The primary end points of period 2 were long-term tolerability and treatment-emergent adverse events.

Patients were recruited from 109 sites in 12 countries, including Bulgaria, Canada, Chile, Czech Republic, Germany, Peru, Poland, Romania, Russia, Spain, Ukraine, and the United States. A total of 730 patients were randomly assigned in period 1 (n=367 FKB327; n=363 RP), among whom 645 were transitioned to period 2 (n=216 FKB327-FKB327; n=108 FKB327-RP; n=108 RP-FKB327; n=213 RP-RP). Mean patient age was 53.3±12.2 years; 77.6% were women, and 85.0% were white. Patient demographics were generally similar across study groups.

At week 24, ACR20 response rates were similar with FKB327 and RP (74.1% and 75.7%, respectively; 95% CI for treatment difference, -7.9 to 4.7). Mean DAS28-CRP scores were also comparable between treatment groups (95% CI for treatment difference, -0.16 to 0.18). The ACR20 response rate remained above 70% for all treatment groups through week 54. In period 1, mean serum drug concentrations were slightly elevated among patients receiving FKB327 compared with patients receiving RP (4124.3 ng/mL vs 3761.7 ng/mL, respectively). Similar rates of positivity for neutralizing antidrug antibodies were observed in the FKB327 (57.9%) and RP (55.5%) treatment groups at week 24. Slightly reduced efficacy of the treatment drug was observed in patients with high antidrug antibody titers.

Overall, 25 patients (5.3%) treated with FKB327 and 34 patients (7.2%) treated with RP reported serious treatment-emergent adverse events. The most commonly reported serious adverse events were infections. Injection site reactions were relatively uncommon, although some patients reported erythema, irritation, or pain after injection.

These study results suggest similar clinical efficacy between FKB327 and RP. The ACR20 response, DAS28-CRP scores, and serum drug concentrations were comparable across study groups. No additional safety signals were observed with FKB327 compared with RP treatment. Further study is necessary to explore treatment options for patients with high antidrug antibody titers, given the reduced efficacy observed for both FKB327 and RP in this circumstance.

“[Overall], these results support the proposal of FKB327 as a candidate biosimilar to RP in patients with active RA,” the investigators concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures


Genovese MC, Glover J, Greenwald M, et al. FKB327, an adalimumab biosimilar, versus the reference product: results of a randomized, phase III, double-blind study, and its open-label extension. Arthritis Res Ther. 2019;21(1):281.