THESSALONIKI, Greece—Flares of latent tuberculosis (TB) and cases of newly acquired TB occasionally occur in rheumatoid arthritis (RA) patients being treated with TNFα inhibitors, even when strict screening criteria have been used. There has been little research on the safety of readministering TNFα inhibitors after bringing TB under control in such patients. Spyros Aslanidis, MD, and colleagues from Hippokration General Hospital in Thessaloniki, Greece, report in Arthritis & Rheumatism that resuming anti-TNF treatment can be a safe option.¹

"Two clear issues are 1) whether it is safe to reintroduce anti-TNFα therapy in patients who have exhibited tuberculosis during the course of their initial treatment, and 2) if so, what is the optimum time point for reintroduction?" Dr. Aslanidis said.

Aslanidis et al reported cases of active TB appearing in 5 of a 180 RA cohort receiving anti-TNFα treatment, all of whom had negative purified protein derivative (PPD) skin test results during the screening prior to beginning therapy. All five patients were hospitalized "for prolonged fever, with clinical symptoms and radiographic evidence of respiratory tract infection." Symptom onset coincided with development of a positive PPD test in 4 of the 5 patients. TB diagnosis was established by lymph node biopsy, lung biopsy, or sputum culture in three patients; TB diagnosis was based on clinical/radiographic criteria and response to treatment in the two remaining patients.

Active TB developed within 6 months of beginning TNF-α inhibitor treatment in three patients and was considered to be reactivation of latent TB. The other two cases developed after 30 months and 46 months of anti-TNF treatment and were thought to be newly acquired TB.

"The prevalence of latent TB is relatively low among the native Greek population; new cases of TB are, however, increasing in number, partly due to rising immigration/repatriation rates," Dr. Aslanidis commented.

The five patients were treated with ethambutol, isoniazid, or a combination of isoniazid and rifampin, and 3 of the 5 patients also received streptomycin. Treatment continued for 6 to 12 months until complete recovery, during which time anti-TNFα treatment was discontinued (infliximab in four patients, adalimumab in one patient) and patients were treated only with low-dose corticosteroids. Methotrexate was begun after the conclusion of TB treatment, but did not control RA flares in three patients. Anti-TNFα treatment was reinitiated immediately after the completion of TB therapy in two of these patients, and 3 years later in the third patient. This produced rapid remission of RA symptoms and laboratory abnormalities.

"All three patients were still receiving anti-TNF therapy at the time of submission of this manuscript (17 to 27 months after reinstitution) and, despite the fact that they are not receiving any prophylactic anti-TB treatment, they show no clinical, chest radiographic, or molecular evidence of relapse of TB infection...," Dr. Aslanidis said. The researchers concluded, "Based on the findings in our three patients in whom reinitiation of anti-TNFα therapy proved to be effective and safe...we propose that readministration of anti-TNF treatment should not be ruled out, and that it could represent a safe option for patients with otherwise uncontrollable RA flares."

Dr. Aslanidis also pointed out that blocking TNF might have some benefits as an adjunct to anti-TB treatment because TNFα is required for the formation and maintenance of granulomas. TB in patients who have been taking TNFα inhibitors typically lacks the orderly, formed granulomas that provide the microenvironment sanctuary for surviving dormant mycobacteria, and may therefore be less likely to undergo future reactivation.

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