For patients with Crohn disease, treatment with BI 695501 was noninferior to adalimumab reference product, with similar safety profiles noted between both treatments, according to the results of an exploratory analysis published in The Lancet Gastroenterology & Hepatology.
Although BI 695501 is biosimilar to adalimumab reference product and has shown similar efficacy, safety, and immunogenicity in treating patients with rheumatoid arthritis and chronic plaque psoriasis, these outcomes have not been measured in Crohn disease. To address this knowledge gap, a team of investigators conducted a phase 3, multicenter, double-blind, parallel-group, active-comparator trial (VOLTAIRE-CD; ClinicalTrials.gov Identifier: NCT02871635) to compare the safety and efficacy of these treatments in patients with moderately to severely active Crohn disease.
The primary endpoint measured the proportion of patients with a clinical response to treatment at week 4, which was defined as a decrease from baseline in Crohn’s Disease Activity Index score (CDAI, ranging from 220-450) of at least 70 points. Secondary outcomes were separated into efficacy and safety outcomes. Efficacy outcomes included the proportion of patients with clinical response and clinical remission (CDAI score <150) at week 24. Safety endpoints included the proportion of patients with adverse events, serious adverse events, adverse events of special interest, and injection-site reactions.
A total of 147 patients were randomly assigned to receive either BI 695501 (n=72) or adalimumab reference product (n=75). Of the patients in the adalimumab cohort, 93% were administered 40 mg/0.4 mL citrate-free formula and 7% were administered 40 mg/0.8 mL formulation. After full analysis modification, 68 patients were included in the BI 695501 cohort and 72 patients were included in the adalimumab cohort.
For patients in the BI 695501 cohort, the median age was 35.0 years, 54% were men, and the median CDAI score at baseline was 297.0. For patients in the adalimumab cohort, the median age was 30.0 years, 57% were men, and the median CDAI score was 296.0.
At week 4, 90% of the BI 695501 group and 94% of the adalimumab group had a clinical response (adjusted risk ratio [RR], 0.945). In a safety analysis including the total original cohort, 45 of 72 patients in the BI 695501 cohort and 42 of 75 patients in the adalimumab cohort had adverse events during weeks 0 to 24; 31 and 34 patients, respectively, had adverse events during weeks 24 to 56.
In weeks 0 to 24, serious adverse events were reported in 6 patients in the BI 695501 group and 8 patients in the adalimumab reference group. In weeks 24 to 56, there were 2 and 9 patients with serious adverse events in the BI 695501 and adalimumab groups, respectively. These adverse events included psoas abscess and hypersensitivity in the BI 695501 group and pulmonary tuberculosis and erythematous rash in the adalimumab group.
Adverse events of special interest from weeks 0 to 24 occurred in 2 patients in each treatment group. These adverse events included acute sinusitis and pulmonary tuberculosis in the BI 695501 group and anal abscess and postoperative would infection in the adalimumab reference group. Weeks 24 to 56 also had 2 patients per group with adverse events of special interest.
Investigators acknowledge that the use of CDAI score as a primary endpoint may be a limitation, as it is subjective in nature.
“The incidences of potentially clinically relevant immunogenic response were similar for both treatment groups, and the development of trough adalimumab concentrations
showed a similar accumulation over time,” the researchers wrote. “The findings of this study supports existing licensure of the biosimilar BI 695501 as an alternative to adalimumab reference product for patients with Crohn’s disease,” the investigators concluded.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Hanauer S, Liedert B, Balser S, Brockstedt E, Moschetti V, Schreiber S. Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn’s disease (VOLTAIRE-CD): a multicentre, randomised, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021;6(10):816-825. doi: 10.1016/S2468-1253(21)00252-1