Study to Evaluate Discontinuation of Biosimilar RA Treatment

August 11, 2020
Tony Hagen

Tony Hagen is senior managing editor for The Center for Biosimilars®.

Japanese investigators say more needs to be known about what happens post treatment with biosimilar infliximab in patients with rheumatoid arthritis (RA).

Japanese investigators hope to shed light on durability of clinical remission in rheumatoid arthritis (RA) following discontinuation of treatment with an infliximab biosimilar (CT-P13, Remsima).

“It is the next great issue whether disease activity can be maintained…after discontinuation of CT-P13, because no evidence is available” regarding the clinical outcome after biosimilar infliximab is stopped in RA, they wrote.

Rheumatoid arthritis is a chronic, systemic inflammatory disease that when uncontrolled can lead to joint destruction and deformity, lowering patients’ quality of life. Advances in the use of biologic disease modifying antirheumatic drugs, including biosimilars, have improved clinical outcomes, leading to low disease activity and clinical remission.

In the ongoing IFX-SIRIUS STUDY I, investigators are evaluating whether continued treatment with biosimilar infliximab is not inferior to treatment with the originator product in maintaining nonclinical relapse. The new study, IFX-SIRIUS STUDY II, continues with the evaluation of what happens once treatment with the biosimilar is stopped.

The clinical findings will be important, the investigators note, because infliximab is a costly drug whether the originator or a biosimilar is used. Therefore, it is important to know if disease activity can be suppressed following discontinuation of the biosimilar in patients with RA.

Previous Findings Show Lasting Benefit

Previous studies have suggested that the disease can be controlled following treatment cessation with antirheumatic drugs, so the investigators expect encouraging findings from IFX-SIRIUS STUDY II. According to findings published in 2010, of 102 patients with RA, 55% of those who attained low disease activity on infliximab were able to discontinue the drug for more than 1 year without radiologically detectable joint destruction.

Results from the HONOR study, reported in 2016, suggested the same long-term, medication-free benefit. The study enrolled 197 patients with RA treated with adalimumab. One year after discontinuation, 79% of patients who began the period with deep remission had not experienced flaring of inflammation and showed no functional or structural damage. The study also found that readministration of the drug to patients with flare-ups was effective in controlling RA.

Despite such findings, more needs to be known about “optimal approaches for discontinuation,” the investigators wrote.

In IFX-SIRIUS STUDY II, disease activity will be measured by musculoskeletal ultrasound as well as by clinical disease activity in order to accurately assess inflammation at the joint level. Investigators will also measure serum levels of cytokines and chemokines to determine whether these biomarkers can predict nonclinical relapse after discontinuation of biosimilar infliximab.

“We expect that a certain proportion of patients with RA will have clinical relapse after discontinuation of CT-P13; thus, we will also evaluate the effectiveness and safety of CT-P13 retreatment in patients with RA who have clinical relapse,” they said.

The prospective, interventional, single-arm, multicenter study based in Japan will begin with enrollment of ≤ 80 patients and baseline screening, followed by evaluations at 3-month intervals and final evaluation at 48 weeks. For enrollment, patients must have been on biosimilar infliximab during the IFX-SIRIUS STUDY I and have experienced a nonclinical relapse during that study period.

Patients will discontinue CT-P13 at points throughout the study period, and if they have a relapse following discontinuation, CT-P13 will be readministered.

The primary end point is the proportion of patients who had clinical relapse during the 48-week period.

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