Switching to CT-P13 Associated With Loss of Response in Patients With Behçet's Disease

A recent case report, published in the European Journal of Rheumatology, showed that switching to biosimilar infliximab resulted in a rapid loss of efficacy in 3 patients with Behçet’s disease (BD), a chronic, relapsing, systemic vasculitis.

Severe clinical manifestations of BD include eye, intestinal, and neurological inflammatory involvement that may be refractory to treatment with corticosteroids or immunosuppressive drugs, and may warrant treatment with infliximab.

When biosimilar infliximab CT-P13 (Inflectra, Remsima) was approved in the European Union, it offered a lower-cost option for treating patients with BD, but in 3 cases observed by the Rheumatology Department of Prato, a referral center for rare rheumatic diseases in Italy, a non-medical switch to CT-P13 in patients’ local health clinics was associated with a relapse of BD.

Case 1

A 32-year-old man with BD who did not respond adequately to corticosteroids, methotrexate, and cyclosporine A was treated with reference infliximab at a dose of 5mg per kg at weeks 0, 2, 6, and every 8 weeks thereafter. His symptoms subsided after the third infusion, and he achieved clinical remission (which was maintained on reference infliximab therapy). Two weeks after switching to CT-P13, the patient developed cutaneous vasculitis with papulopustulosis, oral and genital ulcers, and worsening of visual acuity. He required treatment with subcutaneous adalimumab to resolve the retinal vasculitis.

Case 2

A 40-year-old woman with BD who had bilateral posterior uveitis and cerebral vasculitis achieved stable disease remission with reference infliximab therapy at 5 mg per kg for 5 years. She was then switched to CT-P13 and experienced a loss of response after her third infusion. She experienced posterior uveitis, fever, headache, loss of balance, and cognitive impairment, among other symptoms. Treatment with intravenous methylprednisolone plus adalimumab was required to return the patient to clinical remission.

Case 3

A 26-year-old man with BD had neurological and intestinal involvement of BD that was refractory to treatment with methotrexate. Reference infliximab at a dose of 5 mg per kg allowed the patient to achieve complete disease remission that was maintained for the next 5 years. He was switched to CT-P13, and after the second infusion, oral aphthosis, papulopustulosis, and neurological and intestinal manifestations of BD recurred. Intravenous methylprednisolone and adalimumab were required to return the patient to complete remission over the next 2 months.

The case study’s authors state that, “In the absence of a valid explanation, we could only hypothesize that the rapid failure of [CT-P13] in our 3 patients might be related to the development of ADAs against [the biosimilar.]” While technical problems (such as improper storage or drug solution preparation issues) could be responsible for the loss of efficacy of CT-P13, the authors state that “Our experience with the 3 BD patients who were successfully treated with [reference infliximab] and who experienced recurrence...soon after switching to [CT-P13] appears to reinforce skepticism regarding the exchangeability and automatic substitution of reference [infliximab] with the biosimilar drug."