Review Finds Better Efficacy of Biologics in Trials Without Placebo

Samantha DiGrande

A review was recently conducted among 2 different types of randomized clinical trials in the treatment of rheumatoid arthritis (RA): those comparing reference biologics’ efficacy versus placebo, and those comparing reference biologics’ efficacy versus biosimilars.

A review was recently conducted among 2 different types of randomized clinical trials in the treatment of rheumatoid arthritis (RA): those comparing reference biologics’ efficacy versus placebo, and those comparing reference biologics’ efficacy versus biosimilars. The researchers performed a systematic review of literature and meta-analysis of the data, the results of which will be presented during the American College of Rheumatology (ACR) Annual Meeting in Chicago, Illinois, held from October 19-24, 2018.

The study’s authors searched for randomized, double-blind, placebo-controlled or biosimilar controlled trials in RA. The review included randomized clinical trials in those with inadequate response to methotrexate and other disease-modifying anti-rheumatic drugs. However, randomized clinical trials involving monotherapy, methotrexate-naïve patients, or those who responded inadequately to biologics were excluded. In total, the review included 22 articles: 12 reference—placebo trials and 10 reference–biosimilar trials. The primary endpoint was the American College of Rheumatology’s criteria for a 20% improvement (ACR20).

The treatment timeframe for each group was approximately 24 weeks, and the characteristics of the population such as disease duration, disease activity, seropositivity, and methotrexate dose were similar. The global rates of ACR20 responders in both groups were calculated by performing a meta-analysis.

For the reference—placebo group, the global rate of ACR20 response was 58% (range, 54%-62%). In the reference–biosimilar group, however, the global ACR20 response rate was 70% (64%-76%). The researchers also evaluated the global rate of the American College of Rheumatology 50% (ACR50) response. In the reference–placebo group, ACR50 rate was 34% (30%-39%), whereas the rate for the reference–biosimilar group was 44% (37%-51%).

The researchers concluded that “The efficacy of reference agents is better in recent non-inferiority [randomized clinical trials] where all patients were treated with the reference agents or [a] biosimilar, than in pivotal [randomized clinical trials] where the patients could potentially be treated with the biologic agents or a placebo.” Notably, the authors say that a nocebo effect could explain lower efficacy found in reference—placebo trials.

Reference

Lopez L, Richez C, Truchetet ME, et al. Efficacy of the reference biologic agents in two different types of randomized clinical trials: 1/ the ones comparing their efficacy vs. placebo and 2/ the ones comparing their efficacy vs. biosimilar in rheumatoid arthritis: a systematic review of literature and meta-analysis. Presented at the American College of Rheumatology 2018 meeting, October 19-24, 2018; Chicago, Illinois. Abstract 2520.https://acrabstracts.org/abstract/efficacy-of-the-reference-biologic-agents-in-two-different-types-of-randomized-clinical-trials-1-the-ones-comparing-their-efficacy-vs-placebo-and-2-the-ones-comparing-their-efficacy-vs-biosimilar/.