Adalimumab Biosimilar SB5 Effective in Behçet’s Syndrome-Related Uveitis and IBD, Studies Find

Two new studies have investigated the adalimumab biosimilar SB5 (Imraldi; Samsung Bioepis) in inflammatory bowel disease (IBD; Crohn disease and ulcerative colitis)¹ and non-anterior uveitis associated with Behcet's syndrome (BS).²

According to the authors of the real-world study in IBD, their effectiveness data “shows comparability with the [adalimumab] originator.” Adalimumab drug persistence was 62.5% in patients starting on SB5 and 83.1% in patients switching from the reference product to biosimilar SB5. Those figures, the authors wrote, are “in line with drug persistence data from previous studies with the originator.”

In the retrospective study on BS-associated uveitis, all 8 patients who were treated with SB5 over an average of 16 months experienced complete resolution of inflammation. Retinal vasculitis resolved in all four eyes that were affected at baseline.

Adalimumab is a monoclonal antibody targeting tumor necrosis factor (TNF) alpha. The reference product (Humira) was first approved by the FDA in 2002 and the European Medicines Agency in 2003. Adalimumab biosimilars are currently available in the European Union, but market entry for has been delayed in the US due to additional patents and legal settlements.

Drug persistence in IBD

The investigators noted that several studies have demonstrated the effectiveness and safety of biosimilars to infliximab, another anti-TNF biologic.

However, they wrote, “data on [adalimumab] biosimilars are scarce.” At the time their study was published, they wrote, "no randomized controlled trials comparing a biosimilar to the originator in IBD have yet been published." (Since then, recent data from VOLTAIRE-CD have shown that safety and efficacy were similar in patients with Crohn's disease treated with BI 695501 or the adalimumab reference product, Humira.)

Their retrospective observational cohort study, conducted in Scotland, examined long-term outcomes of 481 patients with IBD taking SB5. Of those, 256 switched from the originator to SB5 (switch cohort), while 225 who were not being treated with adalimumab at baseline started treatment with the biosimilar (start cohort). Notably, their study included 35 patients who underwent a double switch from the reference product to SB5 to another adalimumab biosimilar, ABP 501.

The primary outcome of the study was drug persistence. In the switch cohort, 213 patients (84.6%) remained on the biosimilar after 26 weeks, and at 52 weeks 163 (70.8%) were still being treated with SB5. Over a median 13.7-month follow-up, 90 (35.2%) patients discontinued biosimilar treatment, 46 due to adverse events and 37 due to secondary loss of response. The investigators found no differences in the proportion of patients in clinical remission, or median C-reactive protein, fecal calprotectin, or adalimumab trough levels between baseline, week 26, and week 52 following the switch.

In the start cohort, at week 26, 137 patients (77.8%) remained on SB5 treatment, and 65 (60.3%) remained at 52 weeks. Over a median follow-up of 18.3 months, 81 patients (36%) discontinued SB5 therapy, 22 due to primary non-response, 26 due to secondary non-response, and 24 due to adverse events.

Pain at the injection site was the most frequent adverse event in the switch cohort. Three patients developed a skin rash and 5 patients developed an infection requiring temporary discontinuation of therapy. Of the 256 patients in the switch cohort, 51 patients experienced adverse events that required suspending or discontinuing SB5 therapy. In the start cohort, 39 of the 225 patients experienced any adverse event, the most frequent of which were infections. Of 17 infections, 7 required temporary suspension of treatment, and 10 required permanent discontinuation.

Double switch

The majority of patients in the switch cohort (76.1%), and a minority of patients in the start cohort (3.1%) who discontinued SB5 due to side effects switched to another adalimumab product. Taking these numbers into account, the authors said drug persistence on adalimumab overall was 90.9% and 83.1% at week 26 and 52 in the switch cohort and 80.1% and 62.8% in the start cohort.

The investigators added that 35 patients underwent a double switch from the reference product to biosimilar SB5 and then to biosimilar ABP 501, all of whom underwent the second switch due to side effects on SB5 (33 for pain at injection site, 2 for skin rash). None of these patients discontinued adalimumab therapy over a median follow-up duration of 34 weeks.

SB5 in uveitis

Researchers conducted a retrospective study of eight patients with BS who had active non-anterior uveitis and/or systemic uncontrolled disease or were undergoing a nonmedical switch from the reference product to SB5.

The authors said uveitis is one of the main clinical features of BS, which reduces visual acuity and negatively affects quality of life. However, “the use of monoclonal TNF-α antibodies has significantly improved visual prognosis in BS patients and widened therapeutic alternatives for the management of such a sight-threatening condition.”

The efficacy and safety of SB5 were originally demonstrated in rheumatoid arthritis, which the authors said “may not guarantee extrapolation to other indications, since it is not a very sensitive model for the detection of potential differences” between the biosimilar and reference product. They also mentioned data on SB5 in BS-related uveitis are scarce.

The 8 patients were treated with biosimilar SB5 for an average of 16.38 (standard deviation 3.93) months. In the 12 months prior to initiating adalimumab biosimilar therapy, there were 8 ocular relapses in the 8 patients. No ocular relapses were reported between baseline and the last follow-up visit.

At baseline, 4 of the 16 eyes had active retinal vasculitis, and all 4 had resolved by 3 months of SB5 therapy and remained resolved at the last follow-up. Furthermore, over the 16-month follow-up, “complete resolution of inflammation was observed in all affected eyes.” No adverse events were reported, and median visual acuity did not significantly change from baseline to the last follow-up visit. The investigators concluded SB5 is an effective treatment option for BS-related non-anterior uveitis.

The authors mentioned their findings “should be interpreted with caution” because of the small sample size and other study limitations. However, to their knowledge their study “represents the largest sample of BS patients affected by uveitis and successfully treated with SB5.

References

1. Derikx LAAP, Dolby HW, Plevris N, et al. Effectiveness and aafety of adalimumab biosimilar SB5 in inflammatory bowel disease: outcomes in originator to SB5 switch, double biosimilar switch and bio-naïve SB5 observational cohorts. J Crohns Colitis. 2021;15(12):2011-2021. doi:10.1093/ecco-jcc/jjab100

2. Sota J, Gentileschi S, Perfetti MO, et al. Role of adalimumab biosimilar in the treatment of non-anterior uveitis associated with Behçet's syndrome. Ophthalmol Ther. 2021;10(4):1129-1135. doi:10.1007/s40123-021-00387-6