mycophenolic-acid 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 report outcomes of Vogt-Koyanagi-Harada (VKH) disease from a clinical trial of antimetabolite therapies.. Subanalysis from an observer-masked randomized clinical trial for noninfectious intermediate, posterior, and panuveitis.. setting: Clinical practice at Aravind Eye Hospitals, India.. Forty-three of 80 patients enrolled (54%) diagnosed with VKH.. Patients were randomized to either 25 mg oral methotrexate weekly or 1 g mycophenolate mofetil twice daily, with a corticosteroid taper.. Primary outcome was corticosteroid-sparing control of inflammation at 5 and 6 months. Secondary outcomes included visual acuity, central subfield thickness, and adverse events. Patients were categorized as acute (diagnosis ≤3 months prior to enrollment) or chronic (diagnosis >3 months prior to enrollment).. Twenty-seven patients were randomized to methotrexate and 16 to mycophenolate mofetil; 30 had acute VKH. The odds of achieving corticosteroid-sparing control of inflammation with methotrexate were 2.5 times (95% CI: 0.6, 9.8; P = .20) the odds with mycophenolate mofetil, a difference that was not statistically significant. The average improvement in visual acuity was 12.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. On average, visual acuity for patients with acute VKH improved by 14 more ETDRS letters than those with chronic VKH (P < .001), but there was no difference in corticosteroid-sparing control of inflammation (P = .99). All 26 eyes with a serous retinal detachment at baseline resolved, and 88% achieved corticosteroid-sparing control of inflammation.. The majority of patients treated with antimetabolites and corticosteroids were able to achieve corticosteroid-sparing control of inflammation by 6 months. Although patients with acute VKH gained more visual improvement than those with chronic VKH, this did not correspond with a higher rate of controlled inflammation.

Topics: Adult; Drug Administration Schedule; Enzyme Inhibitors; Female; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Panuveitis; Uveomeningoencephalitic Syndrome; Visual Acuity

To assess the usefulness of mycophenolate mofetil (MMF) (Cellcept, Roche), a potent selective uncompetitive and reversible inhibitor of ionisine monophosphate dehydrogenase involved in purine synthesis, as an immunosuppressive and steroid-sparing agent in the management of ocular inflammatory disease.. Open-label, prospective, uncontrolled pilot study.. Eleven patients with uncontrolled ocular inflammation.. Mycophenolate mofetil, at a dosage of 1 g twice daily, was given in conjunction with steroids, as a steroid-sparing agent, or as an additional agent with cyclosporine (CsA), or instead of CsA or azathioprine.. The inflammatory response, side effects, and toxicity were monitored.. The addition of MMF to immunosuppressive regimens led to the improvement in symptoms and the ability to reduce the dose of prednisone in most patients. Ten of 11 patients showed a favorable response to MMF, with few side effects noted.. These findings suggest that MMF is a useful immunosuppressive drug for controlling ocular inflammation with minimal side effects.

Topics: Adult; Aged; Enzyme Inhibitors; Female; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Male; Middle Aged; Mycophenolic Acid; Panuveitis; Pilot Projects; Prospective Studies; Safety; Scleritis; Treatment Outcome

Topics: Antibiotics, Antineoplastic; Child; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Humans; Mycophenolic Acid; Nephritis, Interstitial; Panuveitis; Time Factors; Uveitis

Vogt-Koyanagi-Harada (VKH) disease is uncommon in the pediatric population and can have an aggressive course with serious visual sequelae. A 12-year-old Han Chinese American female, who presented with mild headaches and panuveitis with diffuse serous retinal detachments, was diagnosed with VKH. Despite treatment with a combination of high-dose systemic corticosteroids, intravitreal triamcinolone injection, and mycophenolate mofetil, ocular inflammation was inadequately controlled. Addition of adalimumab allowed for inflammation remission, improvement of vision, and tapering of systemic corticosteroids. Escalation of immunosuppression until remission appears to be critical in this population. Further research is needed to understand the complex pathophysiology of VKH and investigation for similar efficacy of other anti-tumor necrosis factor-alpha agents will need to be performed.

Topics: Adalimumab; Child; Drug Therapy, Combination; Female; Fluorescein Angiography; Headache; Humans; Mycophenolic Acid; Panuveitis; Remission Induction; Tomography, Optical Coherence; Triamcinolone; Tumor Necrosis Factor-alpha; Uveomeningoencephalitic Syndrome; Visual Acuity

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

To report a case of herpes simplex virus-induced herpetic necrotizing retinitis after placement of a flucinolone acetonide (Retisert) intravitreal implant.. Interventional case report.. Retrospective chart review.. A 22-year-old male with idiopathic unilateral panuveitis since 2002 that was intolerant of systemic immunosuppressive therapy received a flucinolone acetonide implant 6 years later. Intraocular inflammation was completely quiescent until 1 year following the implant, when he developed retinitis. To the authors' knowledge, this is the first reported case of polymerase chain reaction-proven herpetic necrotizing retinitis following implantation of a Retisert device.. Although rare, herpetic necrotizing retinitis can occur in the setting of local ocular immunosuppression with the Retisert intravitreal implant. This potential infection should be considered in the face of recurrent uveitis following Retisert implantation.

Topics: Acyclovir; Antiviral Agents; Azathioprine; Cataract; Drug Implants; Eye Infections, Viral; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Panuveitis; Pregnadienetriols; Retinal Necrosis Syndrome, Acute; Treatment Outcome; Valacyclovir; Valine; Visual Acuity; Young Adult