tacrolimus and Panuveitis

Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated in the posterior structures of the eye. Because NIIPPU is typically a chronic condition, people with NIIPPU frequently require treatment with steroid-sparing immunosuppressive therapy. Methotrexate, mycophenolate, cyclosporine, azathioprine, and tacrolimus are non-biologic, disease-modifying antirheumatic drugs (DMARDs) which have been used to treat people with NIIPPU.. To compare the effectiveness and safety of selected DMARDs (methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and azathioprine) in the treatment of NIIPPU in adults.. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, the Latin American and Caribbean Health Sciences database, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, most recently on 16 April 2021.. We included randomized controlled trials (RCTs) comparing selected DMARDs (methotrexate, mycophenolate, tacrolimus, cyclosporine, and azathioprine) with placebo, standard of care (topical steroids, with or without oral steroids), or with each other.. We used standard methodological procedures expected by Cochrane.. We included 11 RCTs with a total of 601 participants in this review. DMARDs versus control Two studies compared an experimental DMARD (cyclosporine A or enteric-coated mycophenolate [EC-MPS]) plus oral steroid with steroid monotherapy. We did not pool these results into a meta-analysis because the dose of cyclosporine used was much higher than that used in current clinical practice. The evidence is very uncertain about whether EC-MPS plus low-dose oral steroid results in a higher proportion of participants achieving control of inflammation over steroid monotherapy (risk ratio [RR] 2.81, 95% confidence interval [CI] 1.10 to 7.17; 1 study, 41 participants; very low-certainty evidence). The change in best-corrected visual acuity (BCVA) was reported separately for right and left eyes. The evidence for improvement (lower logarithm of the minimum angle of resolution (logMAR) indicates better vision) between the groups is very uncertain (mean difference [MD] -0.03 and -0.10, 95% CI -0.96 to 0.90 and -0.27 to 0.07 for right and left, respectively; 1 study, 82 eyes; very low-certainty evidence). No data were available for the following outcomes: proportion of participants achieving a 2-line improvement in visual acuity, with confirmed macular edema, or achieving steroid-sparing control. The evidence for the proportion of participants requiring cessation of medication in the DMARD versus control group is very uncertain (RR 2.61, 95% CI 0.11 to 60.51; 1 study, 41 participants; very low-certainty evidence). Methotrexate versus mycophenolate We were able to combine two studies into a meta-analysis comparing methotrexate versus mycophenolate mofetil. Methotrexate probably results in a slight increase in the proportion of participants achieving control of inflammation, including steroid-sparing control, compared to mycophenolate at six months (RR 1.23, 95% CI 1.01 to 1.50; 2 studies, 261 participants; moderate-certainty evidence). Change in BCVA was reported per eye and the treatments likely result in little to no difference in change in vision (MD 0.01 logMAR higher [worse] for methotrexate versus mycophenolate; 2 studies, 490 eyes; moderate-certainty evidence). No data were available for the proportion of participants achieving a 2-line improvement in visual acuity. The evidence is very uncertain regarding the proportion of participants with confirmed macular edema between methotrexate versus mycophenolate (RR 0.49, 95% CI 0.19 to 1.30; 2 studies, 35 eyes; very low-ce. There is a paucity of data regarding which DMARD is most effective or safe in NIIPPU. Studies in general were small, heterogenous in terms of their design and outcome measures, and often did not compare different classes of DMARD with each other. Methotrexate is probably slightly more efficacious than mycophenolate in achieving control of inflammation, including steroid-sparing control (moderate-certainty evidence), although there was insufficient evidence to prefer one medication over the other in the VKH subgroup (very low-certainty evidence). Methotrexate may result in little to no difference in safety outcomes compared to mycophenolate.

Topics: Adult; Antirheumatic Agents; Azathioprine; Cyclosporine; Humans; Immunosuppressive Agents; Inflammation; Macular Edema; Methotrexate; Mycophenolic Acid; Panuveitis; Steroids; Tacrolimus

To evaluate the effectiveness of tacrolimus in patients with noninfectious intermediate, posterior, or panuveitis needing a two-immunosuppressive-agent regimen.. Design: Retrospective cohort study. Setting: Two tertiary-care uveitis practices at academic medical centers. Patient population: Thirty-two patients with noninfectious intermediate, posterior, or panuveitides in whom single-agent immunosuppression was inadequate to effect successful corticosteroid sparing. Intervention: tacrolimus, added as the second immunosuppressive agent. Main outcome measure: successful corticosteroid sparing, defined as inactive uveitis at a dose of prednisone ≤7.5 mg/day.. Active uveitis was present in 65.6% of patients at initiation of tacrolimus, and the median time to inactive uveitis was 1.5 months (95% confidence interval 1.2, 4.08). The median time to successful corticosteroid sparing was 3.9 months (95% confidence interval 1.41, 6.67), and by 6 months of follow-up successful corticosteroid sparing was achieved in 75% of patients. Tacrolimus was discontinued for side effects in five patients, three for tremor, and two for hyperglycemia. All side effects were reversible with tacrolimus discontinuation.. Tacrolimus seems to have efficacy as a second immunosuppressive agent in two-immunosuppressive drug regimens, when a single agent does not permit successful corticosteroid sparing. Side effects were reversible with tacrolimus discontinuation.

Topics: Humans; Immunosuppression Therapy; Immunosuppressive Agents; Panuveitis; Retrospective Studies; Tacrolimus; Treatment Outcome; Uveitis

To evaluate the success of single-agent immunosuppression for patients with the posterior uveitides, birdshot chorioretinitis, multifocal choroiditis with panuveitis, and punctate inner choroiditis.. Retrospective case series.. setting: Tertiary care uveitis practices. population: Patients initiated on immunomodulatory therapy. intervention: Patients were treated with prednisone 1 mg/kg and mycophenolate 2 g daily. Prednisone was tapered after 1 month. Immunosuppression was escalated to mycophenolate 3 g daily, with addition of a second agent, as needed, to achieve treatment success. outcome measure: Treatment success, defined as no disease activity with prednisone dose ≤10 mg daily, at 6, 12, and 24 months.. Twenty-seven patients were followed. Mean presentation and 2-year follow-up acuities were 20/41 and 20/42, respectively. For birdshot chorioretinitis, mean (±standard deviation) quantitative Goldmann visual field scores improved from 761 ± 69 degrees (IV/4 isopter) and 496 ± 115 degrees (I/4 isopter) at presentation to 784 ± 57 degrees and 564 ± 125 degrees, respectively. Prednisone was successfully tapered in 95% of patients; mean prednisone doses at 1 and 2 years were 5.3 ± 4.1 and 5.7 ± 4.8 mg/day, respectively. At 2 years, prednisone was discontinued in 11% of patients. Treatment success was achieved in 74% of patients on 1 immunosuppressant, and in an additional 21% of patients on 2 agents, for an overall 95% success rate at 2 years.. Posterior uveitides can be treated with 1 agent in most patients, but the data suggest a need to escalate therapy to higher mycophenolate doses, and in one fifth of cases to add a second agent to maintain disease suppression with acceptably low prednisone doses.

Topics: Adolescent; Adult; Aged; Azathioprine; Chorioretinitis; Choroiditis; Drug Therapy, Combination; Electroretinography; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Multifocal Choroiditis; Mycophenolic Acid; Panuveitis; Prednisone; Retrospective Studies; Tacrolimus; Visual Acuity; Visual Fields