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TB No Barrier to Anti-TNF Treatment

MedpageToday

WASHINGTON -- Patients being treated with tumor necrosis factor (TNF) inhibitors who develop tuberculosis (TB) may safely reinstitute their biologic before completing the lengthy TB treatment regimen, a small retrospective study suggested.

Among a Spanish cohort of patients who restarted anti-TNF treatment after stopping because of active TB, nine did so while still being treated for the infection, while 18 waited until completion, according to Maria Victoria Hernández, MD, of the Hospital Clinical of Barcelona, and colleagues.

Action Points

  • Patients being treated with tumor necrosis factor (TNF) inhibitors who develop tuberculosis (TB) may safely reinstitute their biologic before completing the lengthy TB treatment regimen, a study has found.
  • Note that in none of the 27 patients studied was there a relapse of TB during follow-up of 4 years, suggesting that resumption of biologic therapy may not always need to be deferred.

In none of these 27 patients was there a relapse of TB during follow-up of 4 years, suggesting that resumption of biologic therapy may not always need to be deferred, Hernández said at the annual meeting of the American College of Rheumatology here.

"Tuberculosis is one of the most serious adverse events related to biologic therapy, particularly with the TNF inhibitors," she said.

The cytokine TNF plays an important role in defense against TB infection through several mechanisms, including macrophage activation and formation of granulomas.

Shortly after the introduction of the TNF inhibitors in the 1900s, it became apparent that suppression of this cytokine permitted the reactivation of latent TB.

Compliance with the ensuing recommendations about screening and treatment before initiating treatment has resulted in a substantial decrease in the rate of TB in these patients.

"However, cases are still being diagnosed, and compliance with recommendations does not prevent the occurrence of de novo cases following exposure at any time," Hernández said.

When new infection does develop, current guidelines state that biologic therapy should be withdrawn and the TB treated, but the timing for the reinstitution of the biologic remains unclear, with different groups offering contradictory advice.

For instance, the 2012 recommendations from the American College of Rheumatology simply observe that biologic therapy may be resumed after TB treatment.

In contrast, the guidelines from the British Society for Rheumatology state that patients may continue on biologics if necessary during TB treatment, and the Spanish Society of Rheumatology has said that there is no evidence about the optimal time for resumption.

The Spanish group does suggest that the time until reinitiation of a biologic should be as long as possible, taking into account the disease activity of the underlying inflammatory condition because some patients experience a relapse during TB treatment, Hernández said.

To examine the effects of the timing of restarting biologic therapy, she and her colleagues analyzed data from the Spanish Biologic Therapy Registry, which includes 6,479 patients.

By November 2011, 52 cases of active TB had been reported.

In all cases, the biologic treatment was withdrawn, and in 27, anti-TNF therapy was subsequently restarted.

Among those 27, patients who resumed anti-TNF therapy early were considered group 1, while group 2 consisted of those who completed TB treatment before returning to the biologic.

A total of 15 of the patients were women and mean age was 57. Mean disease duration was 19 years.

The underlying diagnosis was rheumatoid arthritis in 14, ankylosing spondylitis in six, psoriatic arthritis in three, juvenile idiopathic arthritis in two, Behçet's disease in one, and undifferentiated spondyloarthropathy in one.

A total of 20 patients were taking infliximab (Remicade), three were on etanercept (Enbrel), and four were receiving adalimumab (Humira).

Median time to resumption of treatment was 2 months in group 1 and 12 months in group 2.

"When we analyzed disease activity scores at the time of resumption of biologic therapy, we found significantly higher scores in group 1," she said, noting that the intergroup P value was 0.027.

In all but two cases, good control was once again achieved after the resumption of anti-TNF therapy and patients remained on treatment at the last visit.

"In conclusion, treatment for tuberculosis may not be a contraindication for the resumption of anti-TNF therapy, especially in patients who have a relapse of the underlying inflammatory condition and who have had a favorable response to at least 2 months of tuberculosis treatment," she said.

Limitations of this analysis included the small numbers and the lack of data on outcomes if anti-TNF therapy were to continue throughout treatment for TB.

Disclosures

The investigators reported no disclosures.

Primary Source

American College of Rheumatology

Source Reference: Hernández M, et al "When can biological therapy be resumed in patients with rheumatic conditions who develop tuberculosis infection during tumor necrosis factor antagonist therapy? Study based on the BIOBADASER data registry" ACR 2012; Abstract 1641.