Tacrolimus Effective as Second Immunosuppressant for Noninfectious Uveitis

Tacrolimus, used in a dual-immunosuppressive-drug therapy along with an antimetabolite, achieved corticosteroid-sparing for 75% of patients with noninfectious uveitis by 6 months after initiation, according to an analysis published in Retina. In patients for whom a single immunosuppressant did not control inflammation, the calcineurin inhibitor was a useful second agent — and based on US Medicaid data, the study estimated its yearly cost at $549 vs $81,000 with adalimumab.

Researchers examined deidentified electronic records of 32 individuals with intermediate uveitis, posterior uveitis, or panuveitis who were treated and followed at 2 academic tertiary-care uveitis clinics between December 2013 and December 2022. The antimetabolite was mycophenolate in 81.2% of participants. If a second agent was needed, clinicians sometimes chose tacrolimus due to prior data that suggested it can offer comparable effectiveness to cyclosporine, with relatively few side effects.

When participants began taking tacrolimus, 65.6% presented active uveitis. Upon treatment, median time to inactive disease was 1.5 months (95% CI 1.2, 4.08). Investigators targeted a widely-accepted benchmark of tapering prednisone to a dose of 7.5 mg/day or less while sustaining inactive disease, reached at a median of 3.9 months (95% CI 1.41, 6.67).

For many patients, prednisone was tapered to 7.5 mg/day or less gradually, such as 1 mg/day/month. “Although we cannot evaluate it from these data, it has been our clinical impression that this slow rate of taper facilitates prednisone discontinuation without relapse and without corticosteroid withdrawal symptoms,” the investigators explain. Also, previous research indicates tacrolimus better manages uveitis when trough blood level is 5 to 10 ng/mL.

Clinicians discontinued tacrolimus for 5 individuals who experienced tremor or hyperglycemia, but all side effects resolved after stopping the medication. Therapy interruption from side effects was comparable to rates found in studies with antimetabolites or tacrolimus. For uveitis, median tacrolimus doses are 4 mg/day, but can reach 10 mg/day with organ transplants.

Generally, 2-drug immunosuppression is required less often. Limitations of this investigation include a small adult-only cohort, and shorter follow-up for several patients — these factors did not allow subgroup analysis by subtype of uveitis, and detection of rare or long-term side effects. A strength is the study’s 9-year sample.