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More than half of patients with ankylosing spondylitis (AS) who achieved clinical remission on infliximab (Remicade) relapsed when the treatment was withdrawn, a small prospective study found.

Among 36 patients in persistent clinical remission who stopped treatment, 58.3% relapsed within a year, with half of the relapses occurring within 6 months of withdrawal, according to Jordi Gratacós, MD, of the Universitat Autònoma de Barcelona in Spain, and colleagues.

But "unfortunately," no clinical or biological marker could be identified that could predict which patients would stay in long-term remission after treatment withdrawal, the researchers reported online in .

Accordingly, "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," they stated.

The burden of disease in AS is high and the availability of biologic therapies has greatly improved the functionality and quality of life among patients. Approximately 60% of patients experience some response, but only 20% to 30% achieve remission and are symptom-free.

Considerable interest today exists in the question of whether biologic treatment of inflammatory diseases such as AS -- costly and associated with risks such as infection -- can be withdrawn among patients who achieve remission on treatment.

However, most previous studies have not shown success, with high rates of disease reactivation. Factors that have predicted relapse include . In addition, AS includes a wide range of disease manifestations and severity, which also could influence response.

Therefore, to explore the possibility of treatment cessation in a homogeneous group of AS patients, Gratacós and colleagues enrolled 107 patients with definite AS who had received infliximab as a first biologic. Patients' mean age was 42, 70% were men, and 90% were HLA-B27 positive. Disease duration averaged 12 years.

Persistent clinical remission, defined as a disease activity score below 2, normal CRP levels, and no arthritis or other disease manifestations, of at least 6 months' duration was reported in 36 of the 107 patients. Factors that were associated with achieving clinical remission during infliximab treatment included younger age (39 vs 43 years, P=0.05), shorter disease duration (nine vs 14 years, P=0.02), and higher CRP level at the start of treatment (3.41 vs 1.63 mg/dL, P=0.02).

Only one-third of patients remained in clinical remission during the yearlong follow-up (three were lost to follow-up).

Among the 21 patients who relapsed, infliximab was reintroduced and 11 once again achieved remission, but ten did not. Seven of the ten did have a good clinical response, defined as an absence of flare, CRP level below 0.8 mg/dL, and a disease activity score below 4. For the other three, treatment had to be changed to a different anti-tumor necrosis factor agent.

Unlike predictors of response of initial treatment, none of the variables were predictive of loss of clinical remission in relapsers versus non-relapsers, including age (40 vs 37 years), disease duration (9 years for both), CRP (3.9 vs 3 mg/dL), disease activity score (6 for both), and function scores (4 vs 5).

These findings are similar to what was seen in of adalimumab (Humira) in non-radiographic spondyloarthritis. In both that study and the current analysis, dose reduction was not attempted before treatment withdrawal, so the researchers noted that they were unable to rule out the possibility that withdrawal might be successful after intensive dosage lowering. Results also might have differed among patients with longer periods of remission prior to stopping, they acknowledged.

An additional limitation of the study was its small sample size.

"Although the reintroduction of infliximab treatment was safe, half of the patients did not achieve the same clinical response as prior to treatment withdrawal," the authors cautioned.

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