medwireNews: Adding a conventional synthetic disease-modifying antirheumatic drug (DMARD) to first-line systemic corticosteroid therapy (CTC) for nonanterior sarcoidosis-associated uveitis may reduce the risk for treatment failure, suggests research in Ophthalmology.
“Strikingly, CTC-DMARD allowed a significantly decreased risk of treatment failure (for inefficiency or relapse) and a greater corticosteroid-sparing than CTC alone,” report Bahram Bodaghi, from Pitié-Salpêtrière Hospital, Sorbonne University in Paris, France, and colleagues.
They note that “[o]ne of the main challenges in the therapeutic management of sarcoidosis-associated uveitis is the high frequency of relapses (30-60%) during the follow-up,” and that “cortisone-sparing therapy is required in up to 30% of patients,” either because of high-dose corticosteroid dependence or adverse effects of the drug.
A total of 163 patients with a first flare of nonanterior sarcoidosis-related uveitis were included in the retrospective trial, of whom 41 were treated with CTC plus DMARD, namely weekly methotrexate 15–20 mg (n=20), twice daily mycophenolate mofetil 1 g, or daily azathioprine 100–150 mg, and 121 with CTC alone.
The median age of the patients was 54–56 years and 51–57% were women. Sarcoidosis was histologically proven in 55% of patients, presumed in 17%, and probable in 28%, with comparable rates across the two treatment groups. Cystoid macular edema (CME) was present in 52% of patients and vasculitis in 44% with no significant difference between the groups.
At the time of flare, patients in the CTC-DMARD group differed significantly from those in the CTC arm in having a lower prevalence of multifocal choroiditis and a significantly lower daily dose of CTC.
Over a median follow-up of 3.5 years, 13 patients in the CTC-DMARD group experienced treatment failure, defined as treatment discontinuation due to ineffectiveness or relapse, compared with 70 patients in the CTC group over a median follow-up of 4.7 years. This corresponded to treatment-failure free rates of 83% versus 65% at 12 months.
After accounting for the differences in multifocal choroiditis and corticosteroid dose at baseline, patients receiving CTC-DMARD were a significant 2.2-fold more likely to remain free of treatment failure than those receiving CTC alone.
There was no significant treatment difference in terms of improving visual acuity or a reduction in CME, the primary ocular reason for treatment failure, or retinal vasculitis, although in subgroup analysis, 66% of patients with CME at the time of flare in the CTC-DMARD group experienced a reduction in the condition at 3 months, compared with 52% of those in the CTC group.
Bodaghi and colleagues note that, among the secondary outcomes, there was a significant steroid-sparing effect with the addition of DMARD at 3, 6, and 12 months. By 12 months, the median daily dose among patients receiving CTC-DMARD had decreased from 40.0 mg to 5.0 mg, compared with a reduction from 60.0 mg to 7.5 mg for those given CTC only.
They highlight the importance of this finding for patients with sarcoidosis-related uveitis, given that “[c]orticosteroid sparing is essential […] to avoid systemic issues like cardiovascular diseases, diabetes, infections, and osteoporosis, along with serious ocular complications.”
Indeed, withdrawal of CTCs was possible for 38% of patients in the CTC-DMARD group versus 29% of those in the CTC group.
The safety profile was similar for the two treatments, with a comparable adverse event (AEs) rate of 34% and 41% among patients in the CTC-DMARD and CTC groups, respectively. AEs led to a corresponding 13% and 0% of patients discontinuing treatment, namely severe infections, liver cytolysis, and an allergic reaction.
The most common complications were bacterial or viral pulmonary infections and herpes zoster virus, leading the study authors to recommend “thorough vaccination before starting [conventional synthetic] DMARD therapy, particularly with pneumococcal, coronavirus 19, and varicella-zoster virus vaccines.”
They say that adding a conventional synthetic DMARD to CTC therapy “must be prioritized” for patients with nonanterior sarcoidosis-associated uveitis who show “risk factors for treatment failure, poor functional prognosis, or complications of corticosteroids.”
And the team concludes that this treatment strategy “may lead the [International Workshop on Ocular Sarcoidosis] recommendations to consider [conventional synthetic] DMARD in association with corticosteroids as the first-line therapy in non-anterior sarcoidosis-related uveitis.”
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