Stopping treatment with infliximab (brand names, Remsima, Remicade) can lead to relapses in people with ankylosing spondylitis (AS) who are in stable clinical remission, according to a 12-month study.
Reintroduction of infliximab treatment is safe; however, it does not result in the same clinical response prior to treatment withdrawal in a significant number of patients.
The study, “Withdrawal of infliximab therapy in ankylosing spondylitis in persistent clinical remission, results from the REMINEA study,” appeared in the journal Arthritis Research & Therapy.
Therapies targeting the pro-inflammatory molecule tumor necrosis factor (TNF), such as infliximab, have shown effectiveness in patients with AS.
Infliximab is used to reduce inflammation, so as to reduce pain and the progression of AS. It consists of a monoclonal antibody that recognizes and attaches to TNF-alpha, which is involved in inflammation.
Withdrawal of anti-TNF treatments has been associated with disease reactivation in most patients, especially those with high clinical activity and longer disease duration. However, data from recent studies and clinical practice support a dose reduction and potentially stopping these therapies, particularly in patients who maintain good clinical response. Planning a limited duration for anti-TNF treatments could be beneficial given their high cost and potential long-term side effects.
Researchers aimed to better understand how long AS patients maintained a good clinical response, or absence of flares, after anti-TNF withdrawal and to evaluate the effects of treatment reintroduction. The team also analyzed the characteristics of patients who did not present clinical relapse.
Specifically, they focused on patients who received infliximab as first-line treatment and presented clinical remission over at least six months.
The study was conducted in 23 hospitals in Catalonia, Spain. Information such as disease duration and activity, spine global and nighttime pain, levels of the inflammatory marker C-reactive protein (CRP) and erythrocyte sedimentation rate — also a way to assess inflammation — was collected at baseline and every 6–8 weeks over 12 months.
A total of 107 patients — 72% men, mean age 41.8 years, 11.9 years of disease duration — were identified, 36 of whom (34%) achieved persistent clinical remission over six to 12 months and thereby discontinued treatment with infliximab.
Of these 36 patients, only 12 (33.3%) remained free of clinical relapse during follow-up. Half of the relapses occurred within six months of infliximab withdrawal. The 21 patients who presented clinical relapse (58.3%; three others were lost to follow-up) restarted treatment with infliximab, which was not associated with relevant side effects or infusion reactions.
Eleven of these patients (52%) achieved clinical remission again, but 10 did not. Among these, seven had good clinical response after resuming infliximab, as reflected by no flare-ups, CRP level below.8 mg/dl and a Bath Ankylosing Spondylitis Disease Activity Index score lower than 4. However, the treatment was ineffective in three patients (14%), which made the clinicians switch to a different anti-TNF therapy.
The data further showed that the patients with persistent clinical remission on infliximab were significantly younger (mean age 38.5 vs. 43.4 years), had longer disease duration — 8.9 vs. 13.7 years — and higher CRP levels (3.41 vs 1.63 mg/dl) at the start of treatment compared to those with no remission.
However, no significant differences were seen between patients who remained free of clinical relapse after treatment withdrawal and those who did not.
“Overall, the results we reported here suggest that the decision to withdraw treatment should be taken with considerable caution, and it seems unreasonable to propose withdrawal as an objective of the treatment strategy, at least at present, in the absence of any objective predictive factors of persistent clinical remission after treatment withdrawal,” the scientists wrote.
Among the study’s limitations, the researchers mentioned the small sample size, which precluded the determination of factors associated with persistent remission or having a flare-up after infliximab withdrawal.