Study Reports 24% Discontinuation Rate After Switching From Remicade to Biosimilar CT-P13

A Dutch study recently published in Arthritis and Rheumatology reports that 24% of patients with rheumatoid arthritis (RA), psoriatic arthritis (PA), and ankylosing spondylitis (AS),who switched from originator infliximab (Remicade) to CT-P13, an infliximab biosimilar, discontinued the biosimilar by their 6-month follow-up, mainly for reasons researchers termed “subjective” health complaints.

Researchers, led by Lieke Tweehuysen, MD, attributed the discontinuation of the biosimilar to a possible nocebo effect (in which a patient’s negative expectation causes a treatment to have a more negative effect than it otherwise would), and/or incorrect causal attribution (in which AEs or a loss of efficacy occurring independent of a drug switch are attributed to the biosimilar). Both effects occur in clinical practice, where patients and physicians are aware that a biosimilar is being used. In clinical trials, this process is typically “blinded,” and patients and physicians are unaware of who is receiving biosimilars.

Tweehuysen and colleagues’ multicenter, prospective cohort study included 222 patients treated with the reference infliximab, 192 of whom agreed to transition to the biosimilar CT-P13. Seventy-five patients had RA, 50 had PA, and 67 had AS. Patients’ median disease duration was 14 years, and median treatment with infliximab was 7 years. Throughout the study period, all patients received usual care, disease activity monitoring, and adjustments to treatment to meet treatment targets.

After 6 months, nearly a quarter of the patients who had switched to the biosimilar discontinued CT-P13. Of the 47 patients who discontinued CT-P13:

• 26 discontinued because of a patient-perceived lack of efficacy
• 11 did so because of AEs
• 10 cited both of the above reasons

After discontinuation, 37 patients restarted Remicade, 7 switched to another biologic drug, and 3 remained off of biologic drugs.

At follow-up, the researchers assessed changes in patients’ disease activity score in 28 joints and C-reactive protein (DAS28-CRP), Bath Ankylosing Spondylitis Disease Activity Index scores (BASDAI), CRP levels, and anti-infliximab antibody levels (a measure of immunogenicity), and documented reported adverse events (AEs). They found the following:

• DAS28-CRP remained stable from baseline through month 6 at 2.2 (standard deviation [SD] 0.9) to 2.2 (SD 0.8) (difference, 0.0; 95% confidence interval [CI]; range, -01. to 0.2)
• BASDAI increased from 3.8 (SD 2.1) to 4.3 (SD 2.1) (difference, 0.5; 95% CI; range, 0.1 to 0.9)
• CRP and anti-infliximab antibody levels did not change

The researchers said that the increases seen in the DAS28 score were caused by higher tender joint counts and patient global disease activity scores, which are subjective assessments, and not by changes in objective measures such as swollen joint counts and CRP levels.

Prior to CT-P13 discontinuation, tender joint count, patients’ global disease activity, and BASDAI were increased compared with baseline, the researchers noted. The AEs most frequently reported by patients were arthralgia, fatigue, pruritis, and myalgia.

The study’s results were limited by the small number of patients (30) who did not switch to the biosimilar; these patients could have been used as a control group if there had been greater numbers.

Communication between clinicians and patients appears to be the determining factor of the success of transitioning to a biosimilar in daily practice, the researchers believe, and they recommend that physicians and pharmacists receive training in methods to reassure patients who experience subjective changes when switching to a biosimilar from originator biologicals.