Interleukin-1 receptor antagonist anakinra as treatment for paradoxical responses in HIV-negative tuberculosis patients: A case series

Abstract

Background: Paradoxical inflammatory responses can occur during microbiologically successful antituberculous therapy. Optimal treatment is unknown, but corticosteroids are used most often. It is likely that interleukin-1 (IL-1) plays a central role in the development of these paradoxical responses, and if corticosteroids fail or are undesirable because of adverse effects, anti-IL-1 therapy may therefore be a rational choice.

Methods: We present seven HIV-negative tuberculosis patients with paradoxical responses, two with exclusively pulmonary and five with extrapulmonary tuberculosis. All had received corticosteroids, with unsatisfactory effect. Patients were treated with the IL-1 receptor antagonist anakinra and monitored for reduction of fever and inflammatory markers, imaging evidence of stabilization or regression of lesions, and respiratory improvement.

Findings: Six patients had anemia and four patients had lymphopenia at the start of the antituberculosis treatment. Fever was present in six patients at the moment of paradoxical response. Anakinra resulted in the decrease of fever within days, followed by resolution of symptoms and radiological improvement in five patients. Anakinra induced neutropenia, necessitating its cessation in two patients, who recovered quickly afterward.

Conclusion: Anakinra can be considered in HIV-negative tuberculosis patients with paradoxical responses when steroids fail or are undesired. Given its favorable safety profile and reversible side effects, it is conceivable that anakinra might also be used as first-line adjuvant treatment for paradoxical responses.

Funding: A.v.L. and R.v.C. are supported by National Institutes of Health (R01AI145781).

Keywords: Translation to patients; anakinra; interleukin-1; paradoxical response; tuberculosis.