Dataset Information

Mycophenolate sodium in the treatment of corticosteroid-refractory non-infectious inflammatory uveitis (MySTRI study).

ABSTRACT:

Objectives

To evaluate the therapeutic effect and safety profile of next generation mycophenolate sodium (MPS), which is different from mycophenolate mofetil with an enteric-coated formulation, in corticosteroid-refractory non-infectious inflammatory uveitis (CRU) patients.

Methods

Prospective, uncontrolled, open-label interventional case series. Forty consecutive patients at a tertiary uveitis referral centre received 6 months of oral MPS as the treatment regimen with follow-up 12 months. The main outcome measures were best-corrected visual acuity (BCVA), inflammatory index, steroid-sparing effect of tapering prednisone to ≤10 mg daily and side effects.

Results

Mean age of enroled patients was 49 (49 ± 13) years and 29 (72.5%) were female. Thirty-six (90.0%) had bilateral disease. There were 0 (0%) anterior uveitis, 2 (5.0%) intermediate uveitis, 22 (55.0%) posterior uveitis, and 16 (40.0%) panuveitis. Vogt-Koyanagi-Harada disease was the most common diagnosis (17/40, 42.5%), followed by idiopathic panuveitis (8/40, 20%) and idiopathic retinal vasculitis (5/40, 12.5%). LogMAR BCVA improved from 0.9 (SD = 0.09) to 0.31 (SD = 0.08) after 6 months of MPS with good steroid-sparing effect (p = 0.012). Further maintenance in LogMAR BCVA was evident after MPS discontinuation from 6th month to 12th month, from 0.31 (SD = 0.08) to 0.33 (SD = 0.07), respectively (p = 0.81). MPS was the only immunosuppressive drug needed to reach quiescent state in 29 patients (72.5%). The drug-related safety profile was satisfactory.

Conclusion

MPS is an effective steroid-sparing drug for the treatment of CRU. The effect seen was not only during the 6 months of therapy, but also extended to 12 months to maintain BCVA and inflammation control. The side effects were acceptable.

SUBMITTER: Chen TS

PROVIDER: S-EPMC7784879 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Mycophenolate sodium in the treatment of corticosteroid-refractory non-infectious inflammatory uveitis (MySTRI study).

Chen Tony S TS Tsang Wing Man WM Enkh-Amgalan Ijilmurun I Hwang Yih-Shiou YS

Eye (London, England) 20200706 11

<h4>Objectives</h4>To evaluate the therapeutic effect and safety profile of next generation mycophenolate sodium (MPS), which is different from mycophenolate mofetil with an enteric-coated formulation, in corticosteroid-refractory non-infectious inflammatory uveitis (CRU) patients.<h4>Methods</h4>Prospective, uncontrolled, open-label interventional case series. Forty consecutive patients at a tertiary uveitis referral centre received 6 months of oral MPS as the treatment regimen with follow-up 1 ...[more]

PMID: 32632297

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Project description: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.

Project description:BACKGROUND:Refractory non-infectious uveitis is a serious condition that leads to ocular complications and vision loss and requires effective systemic treatment to control disease. The effectiveness of long-term infliximab [IFX] in refractory non-infectious childhood uveitis and the impact of treatment adherence on disease control were evaluated. METHODS:Retrospective, single-center study between December 2002 and April 2016 of 27 children with refractory non-infectious uveitis [17 with juvenile idiopathic arthritis, JIA] treated with long-term IFX [9+ months]. Disease activity was assessed prior to and while on IFX using the Standardization of Uveitis Nomenclature [SUN]. Number of visits per year with active uveitis was analyzed by repeated measures logistic regression analysis from 2 years prior to IFX initiation or from onset of uveitis until most recent visit on IFX. Incomplete treatment adherence was assessed for each visit and defined as any deviance in corticosteroid use, prescribed infusion frequency, and/or follow-up examination frequency. RESULTS:Primary outcomes were sustained uveitic and systemic disease control prior to and during IFX treatment and the impact of incomplete adherence on uveitic disease control while on IFX. Secondary outcomes included corticosteroid and glaucoma medication requirement, ocular complications and need for surgical intervention. Mean age at IFX initiation was 10.4 ± 4.5 years; initial mean dose was 6.6 ± 2.2 mg/kg [and given at weeks 0, 2, 4 and q4 weeks thereafter for 93%]. Median duration on IFX was 35 [range 9-128] months. Prior to IFX, 14/27 patients had failed adalimumab ± methotrexate [MTX]; 21/27 failed MTX. IFX led to uveitis control in 89% and arthritis control in 76% (13/17). The odds ratio of having controlled disease after IFX was 4.1 (2.6, 6.4) compared to pre-treatment visits. Topical corticosteroids and glaucoma medications were statistically decreased (p = 0.007 right eye [OD], 0.003 left eye [OS] and p = 0.001 OD, p = 0.028 OS respectively). Incomplete adherence to treatment showed 10.3 times greater odds (7.1, 15.0) of having disease activity than full adherence. CONCLUSIONS:This study adds significantly to the IFX literature by documenting outstanding uveitis control with long-term IFX treatment in non-infectious pediatric uveitis patients. Higher dosage and shorter interval were utilized without adverse effects. Importantly, this is the first study, to our knowledge, to document the significant impact of treatment adherence on uveitis control.

Project description:PurposeTo evaluate the role of vitreomacular adhesion (VMA) in visual and anatomic outcomes in patients with non-infectious uveitis.DesignPhase 2 clinical trial PARTICIPANTS: Data from the Safety, Tolerability, and Efficacy of Tocilizumab in Patients with Non-infectious Uveitis (STOP-Uveitis) study was analyzed.MethodsIn the STOP-Uveitis study, patients with non-infectious uveitis (NIU) received monthly intravenous infusions of either 4 or 8 mg/kg tocilizumab until month 6 (M6). Spectral domain optical coherence tomography (SD-OCT) images of patients that completed M6 of the study were analyzed at baseline to stratify the patients by the presence (VMA+) or absence (VMA-) of VMA. Patients with vitreomacular traction (VMT) or epiretinal membrane causing structural abnormalities within center 1 mm were excluded. All images were graded by two independent graders.Main outcome measuresMean change in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and vitreous haze (VH) at M6.ResultsOut of 37 patients randomized in the STOP-Uveitis study, 48 eyes (27 patients) were eligible based on the study criteria. At baseline, 19 eyes were classified as VMA+, and 32 eyes were classified as VMA-. The distribution of two doses of TCZ (4 mg/kg and 8 mg/kg) were similar between the two groups. At M6, the mean improvement in BCVA was 2.00 ± 5.3 and 6.50 ± 7.98 letters in the VMA+ and VMA- groups, respectively (p = 0.02). The mean improvement in CRT was 34.85 ± 72.36 and 80.37 ± 157.21 μm in the VMA+ and VMA- groups, respectively (p = 0.18). Similarly, the mean change in VH was - 0.65 ± 0.47 and - 0.76 ± 0.71 in the VMA+ and VMA- groups, respectively (p = 0.32). Out of 16 eyes with VMA at baseline, 3 eyes developed posterior vitreous detachment (PVD) at M6. The mean change in BCVA was significantly higher (p = 0.02), while CRT and VH score were similar (p > 0.05) in eyes with PVD compared to eyes with persistent VMA.ConclusionsThe absence of VMA or development of PVD in eyes with VMA seems to have a beneficial effect on the vision of subjects receiving treatment for uveitis. Therefore, patients with uveitis should be assessed using SD-OCT for the presence of vitreomacular interface abnormalities.

Project description:BackgroundNon-infectious uveitis represents a sub-type of intraocular inflammation often associated with disorders of immune dysregulation. If untreated, the intraocular inflammation may progress to severe visual impairment and blindness. Current treatment is heavily reliant on systemic corticosteroid, often at doses associated with severe side effects. There is a need for efficacious corticosteroid-sparing immunomodulatory therapy for these patients. Current immunomodulators include various immunosuppressants and biologics but mammalian target of rapamycin (mTOR) inhibitors (such as sirolimus and everolimus) may also be contenders for this role. The systematic review proposed here will evaluate the evidence for the use of sirolimus and everolimus in the context of non-infectious uveitis.Method/designStandard systematic review methodology will be used to identify, select and extract data from any comparative or non-comparative study of mTOR inhibitors in patients with non-infectious uveitis excluding case reports. Searches of bibliographic databases (MEDLINE, EMBASE, The Cochrane Library and CINAHL) and clinical trials registers will be performed, with no restriction on language or date of publication. Translation of non-English language articles will be undertaken where necessary. The primary outcome of interest will be uveitis activity as measured by vitreous haze. Secondary outcomes will include other pre-specified measures of uveitis activity (such as anterior chamber cells or central macular thickness) best corrected visual acuity, heath-related quality of life, requirement for concurrent treatment and adverse events. Risk of bias assessment will be performed appropriate to each study design. Study selection, data extraction and risk of bias assessment will be undertaken by two reviewers independently. Data will be grouped, tabulated and narratively synthesised. Meta-analysis will be undertaken where appropriate clinical and methodological homogeneity exists. The review will be published according to PRISMA guidance.DiscussionStudies of various designs have investigated the clinical use of mTOR inhibitors for non-infectious uveitis, and a large international randomised controlled trail of sirolimus for non-infectious uveitis is due to report. The findings of this systematic review will help inform ophthalmologists and aid the improvement of treatment protocols for non-infectious uveitis with regard to the use of mTOR inhibitors.Systematic review registrationPROSPERO CRD42017056390.

Dataset Information

Mycophenolate sodium in the treatment of corticosteroid-refractory non-infectious inflammatory uveitis (MySTRI study).

Objectives

Methods

Results

Conclusion

Publications

Mycophenolate sodium in the treatment of corticosteroid-refractory non-infectious inflammatory uveitis (MySTRI study).

Similar Datasets

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