@article {1181, title = {Association between Quality of Life and Visual Acuity in a Randomized Clinical Trial of Patients with Uveitis Taking Antimetabolites.}, journal = {Ocul Immunol Inflamm}, year = {2023}, month = {2023 Feb 07}, pages = {1-9}, abstract = {

PURPOSE: To evaluate how changes in visual acuity are associated with changes in quality of life (QoL) among patients with non-infectious uveitis taking antimetabolites.

METHODS: This secondary analysis of the multicenter First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial involves 216 participants randomized to methotrexate or mycophenolate mofetil. Vision-related (NEI-VFQ and IND-VFQ) and health-related (PCS and MCS SF-36v2) QoL and visual acuity were measured at baseline and 6-month primary endpoint.

RESULTS: Visual acuity was significantly associated and correlated with all QoL measures (Spearman correlation coefficients\ =\ 0.5, 0.5, 0.3, and 0.4 for NEI-VFQ, IND-VFQ, SF-36v2 MCS and PCS, respectively). All observed changes in QoL met or exceeded the minimal clinically important difference definition on each scale. Treatment group was not significantly associated with any QoL measure.

CONCLUSION: By adding insight beyond visual acuity, QoL provides a more comprehensive picture of the patient experience during uveitis treatment. QoL = quality of life; VR-QoL = vision-related quality of life; HR-QoL = health-related quality of life; FAST = First-line Antimetabolites as Corticosteroid Sparing Treatment; NEI-VFQ = National Eye Institute Visual Functioning Questionnaire; IND-VFQ = Indian Visual Functioning Questionnaire; SF-36v2 = Medical Outcomes Study 36-Item Short Form Survey; PCS = physical component score; MCS = mental component score; 95\% CI = 95\% confidence interval; MCID = minimal clinically important difference.

}, issn = {1744-5078}, doi = {10.1080/09273948.2023.2169714}, author = {Chattopadhyay, Aheli and Rathinam, S R and Gonzales, John A and Kelly, Nicole K and Thundikandy, Radhika and Kanakath, Anuradha and Murugan, S Bala and Vedhanayaki, R and Lim, Lyndell L and Suhler, Eric B and Al-Dhibi, Hassan A and Doan, Thuy and Ebert, Caleb D and Porco, Travis C and Acharya, Nisha R} } @article {1171, title = {Reduced Dose Methotrexate and Mycophenolate Mofetil in Noninfectious Uveitis: A Sub-Analysis from the First-Line Antimetabolites as Steroid Sparing Therapy (FAST) Trial.}, journal = {Ocul Immunol Inflamm}, year = {2023}, month = {2023 Jan 26}, pages = {1-6}, abstract = {

PURPOSE: Some patients taking methotrexate (MTX) or mycophenolate mofetil (MMF) experience intolerable side effects at full doses. We evaluated whether dose reduction affected treatment outcomes in uveitis patients.

METHODS: Subanalysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial. Patients were randomized to receive MTX (25 mg weekly) or MMF (3\ g daily). A pre-specified dose reduction protocol could be employed for intolerable side effects. Primary analysis was performed at 6\ months.

RESULTS: 43/194 patients (22\%) required dose reduction. 88/151 patients (58\%) on maximum doses and 32/43 patients (74\%) on reduced doses were deemed treatment successes at 6 months. The odds ratio point estimate (1.60, 95\% CI 0.72-3.74) favored dose-reduction but this was not significant. Following reduction, adverse events improved at the subsequent study visit (79 events reduced to 63 events).

CONCLUSION: Dose reduction of antimetabolites was not associated with worse outcomes in this subanalysis of a uveitis trial.

}, issn = {1744-5078}, doi = {10.1080/09273948.2023.2165949}, author = {Sura, Amol A and Sun, Yuwei and Reddy, Amit K and Rathinam, S R and Gonzales, John A and Thundikandy, Radhika and Vedhanayaki, Rajesh and Kanakath, Anuradha and Murugan, Bala and Doan, Thuy A and Lim, Lyndell L and Suhler, Eric B and Al-Dhibi, Hassan A and Acharya, Nisha R} } @article {1231, title = {Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial.}, journal = {J Ophthalmic Inflamm Infect}, volume = {13}, year = {2023}, month = {2023 Jun 09}, pages = {29}, abstract = {

BACKGROUND: The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis.

MAIN BODY: This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF.

CONCLUSION: Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics.

}, issn = {1869-5760}, doi = {10.1186/s12348-023-00350-5}, author = {Reddy, Amit K and Miller, D Claire and Sura, Amol A and Rathinam, S R and Gonzales, John A and Thundikandy, Radhika and Kanakath, Anuradha and Murugan, Bala and Vedhanayaki, Rajesh and Lim, Lyndell L and Suhler, Eric B and Doan, Thuy and Al-Dhibi, Hassan A and Goldstein, Debra A and Arellanes-Garcia, Lourdes and Acharya, Nisha R} } @article {896, title = {Time to Uveitis Control with Methotrexate and Mycophenolate Mofetil.}, journal = {Ophthalmology}, year = {2022}, month = {2022 Jan 24}, abstract = {

This subanalysis from the First-line Antimetabolites as Steroid-sparing Treatment Trial found no significant difference in the time to achieve a corticosteroid-sparing dosage of prednisone for patients with noninfectious uveitis treated with methotrexate versus mycophenolate mofetil.

}, issn = {1549-4713}, doi = {10.1016/j.ophtha.2022.01.020}, author = {Bui, Anh D and Kong, Christina L and Kelly, Nicole K and Rathinam, S R and Gonzales, John A and Thundikandy, Radhika and Kanakath, Anuradha and Murugan, Bala and Vedhanayaki, R and Lim, Lyndell L and Suhler, Eric B and Al-Dhibi, Hassan A and Doan, Thuy and Acharya, Nisha R} } @article {41, title = {Effect of Corticosteroid-Sparing Treatment With Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients With Uveitis: A Randomized Clinical Trial.}, journal = {JAMA}, volume = {322}, year = {2019}, month = {2019 09 10}, pages = {936-945}, abstract = {

Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective.

Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018.

Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109).

Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1\%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome.

Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5\%) women), 194 (89.8\%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7\%) patients in the methotrexate group vs 56 (57.1\%) in the mycophenolate group (difference, 9.5\% [95\% CI, -5.3\% to 21.8\%]; odds ratio [OR], 1.50 [95\% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4\%) in the methotrexate group vs 42 (55.3\%) in the mycophenolate group (difference, 19.1\% [95\% CI, 3.6\% to 30.6\%]; OR, 2.35 [95\% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3\%) in the methotrexate group vs 14 (63.6\%) in the mycophenolate group (difference, -30.3\% [95\% CI, -51.6\% to 1.1\%]; OR, 0.29 [95\% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0\%) in the methotrexate group and 8 patients (7.4\%) in the mycophenolate group.

Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis.

Trial Registration: ClinicalTrials.gov Identifier: NCT01829295.

}, keywords = {Adult, Anti-Inflammatory Agents, Drug Therapy, Combination, Enzyme Inhibitors, Female, Humans, Immunosuppressive Agents, Liver Function Tests, Male, Methotrexate, Middle Aged, Mycophenolic Acid, Prednisolone, Uveitis}, issn = {1538-3598}, doi = {10.1001/jama.2019.12618}, author = {Rathinam, S R and Gonzales, John A and Thundikandy, Radhika and Kanakath, Anuradha and Murugan, S Bala and Vedhanayaki, R and Lim, Lyndell L and Suhler, Eric B and Al-Dhibi, Hassan A and Doan, Thuy and Keenan, Jeremy D and Rao, Maya M and Ebert, Caleb D and Nguyen, Hieu H and Kim, Eric and Porco, Travis C and Acharya, Nisha R} }