Biologic disease-modifying antirheumatic drugs have been the cornerstone of therapy for patients with rheumatoid arthritis (RA) for more than a decade. Although highly effective, these therapies can be expensive and access to them may be limited for some patients. As a result, there continues to be high interest in biosimilars, which have the potential to alleviate some of the financial burden associated with the high cost of treatment and increase patient access to biologic therapies.
According to the results of a recent clinical trial, the adalimumab biosimilar SB5 demonstrated similar efficacy, safety, and pharmacokinetics compared with adalimumab in patients with moderate-to-severe RA (Weinblatt ME, et al. Arthritis Rheumatol. 2018;70:40-48).
The phase 3, randomized, double-blind, parallel-group study enrolled 544 patients with moderate-to-severe RA that was not well-controlled on methotrexate. Patients were randomized 1:1 to SB5 or reference adalimumab at a dosage of 40 mg subcutaneously every other week for 24 weeks. The full analysis included 542 patients (269 in the SB5 arm and 273 in the adalimumab arm). In addition, the per-protocol set included 476 patients (239 in the SB5 arm and 237 in the adalimumab arm).
At baseline, both treatment arms were well-balanced in terms of demographic and disease characteristics, with the exception of slightly younger patients in the SB5 group compared with the reference adalimumab group (mean age, 49.8 years vs 52.5 years, respectively). There were no significant differences in baseline characteristics between younger and older patients.
The primary efficacy end point of American College of Rheumatology 20% (ACR20) improvement in response at week 24 was almost identical between the 2 treatment groups for the per-protocol set—72.4% for SB5 versus 72.2% for the reference product. These results were similar in the full analysis set (ACR20 of 68% and 67.4%, respectively).
All other secondary end points were comparable between groups, including ACR50, ACR70, mean change in disease activity scores from baseline to week 24 on the Disease Activity Score 28, the Simplified Disease Activity Index, and the Clinical Disease Activity Index. Remission rates and proportion of patients with low disease activity were also similar between groups, regardless of the measure of disease activity used.
“The findings from this study showed equivalent efficacy between SB5 and the adalimumab reference product, as demonstrated by the ACR20 response rates at week 24 and other secondary end points at week 24,” said lead author Michael E. Weinblatt, MD, Co-Director of Clinical Rheumatology at Brigham & Women’s Hospital, Boston, MA, in an interview with Value-Based Care in Rheumatology.
Pharmacokinetic profiles of the 2 drugs were comparable (including mean Ctrough values up to week 24) as was immunogenicity at week 24, with antidrug antibodies developing in 33.1% of the SB5 group and 32% of the adalimumab group.
Adverse events (AEs) were similar between groups and were as expected; the majority of these events were mild to moderate in severity. Overall, 35.8% of patients in the SB5 group and 40.7% of those in the reference adalimumab group experienced AEs up to week 24. The most common AEs were nasopharyngitis, headache, bronchitis, and increased alanine aminotransferase level.
AEs considered to be related to the study drugs were reported in 10.1% of patients treated with SB5 and 11.7% of those treated with reference adalimumab. Serious AEs were reported in 1.1% of the SB5 group and 2.9% of the reference adalimumab group. No patient developed active tuberculosis. Up to week 24, the percentage of patients experiencing AEs leading to treatment discontinuation was lower in the SB5 group than in the reference adalimumab group (0.7% vs 3.7%, respectively).
SB5 is currently approved as a biosimilar for adalimumab by the European Commission for the same indications as adalimumab, but has not yet been approved by the FDA.
“In the United States, the biosimilar to adalimumab is not available, since the reference product is under patent. But it is likely that rheumatologists and patients will shift toward a biosimilar when available if there is a significant cost differential,” Dr Weinblatt said.