Adalimumab Could Help Treat Corticosteroid- and Infliximab-Resistant IRIS

Although corticosteroids are a mainstay of treatment for immune reconstitution inflammatory syndrome (IRIS)—a paradoxical clinical worsening of a known condition or the appearance of a new condition after a patient with HIV initiates antiretroviral therapy (ART), frequently associated with mycobacteria that can cause tuberculosis (TB)—some patients with HIV are refractory to corticosteroid therapy.

There is no clear guideline on how to treat these patients, although some limited evidence has suggested that infliximab may be useful in treating IRIS. While tumor necrosis factor (TNF) deficiency is associated with a higher incidence of TB, excessive production of TNF is associated with an exaggerated inflammatory response that can result in mycobacterial IRIS. However, little known about patients whose IRIS is refractory to infliximab.

Now, a recently published case study suggests that adalimumab may be useful in treating patients whose IRIS fails to respond adequately to either corticosteroids or infliximab. The case study reports that a 51-year-old man was diagnosed with HIV infection in 2007, declined treatment, and presented in 2016 with symptoms that, once investigated, revealed miliary TB and 2 frontal cerebral tuberculomas that later tested positive for Mycobacterium tubuculosis. He underwent treatment for TB and, 3 weeks later, received prednisolone for prophylaxis against IRIS. After TB treatment commenced, he began to receive ART.

After 6 weeks of therapy for TB and 3 weeks of ART, he began to taper the corticosteroid and re-presented with high fevers that were eventually diagnosed as IRIS. An increase of prednisolone did not reduce his fevers, so 300 mg of intravenous infliximab was given, but the patient did not improve after 2 doses of infliximab 2 weeks apart. Next, methylprednisolone was given at 500 mg daily for 3 days, but the patient did not improve.

Infliximab was then discontinued, and a subcutaneous injection of adalimumab was given. Two days after the first dose of adalimumab, the patient’s fever reduced, and his neurological signs and symptoms resolved in 48 hours. He continued to receive adalimumab every 2 weeks for 3 months, and the corticosteroid was withdrawn. At a 7-month follow-up, the patient remained well while continuing ART.

“In our patient, interrupting very active inflammation and granuloma formation by TNF blockade may have discouraged the exaggerated immune response, which is important to the development of IRIS, while enhancing bacteria killing by maximizing drug penetration into the granulomas,” say the case study’s authors. “Our case demonstrates that adalimumab is not only effective in controlling IRIS, but that it does so without interfering with mycobacterial or HIV infection control.”

Reference

Lwin N, Boyle M, Davis JS. Adalimumab for corticosteroid and infliximab-resistant immune reconstitution inflammatory syndrome in the setting of TB/HIV coinfection [published online January 30, 2018]. Open Forum Infect Dis. doi: 10.1093/ofid/ofy027.