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Few data exist for the use of golimumab in patients whose uveitis does not respond to adalimumab, a first-line biologic choice in refractory juvenile idiopathic arthritis-associated uveitis.
Golimumab (GLM) was effective in treating patients with juvenile idiopathic arthritis (JIA) who experienced loss of response (LOR) to adalimumab (ADA), according to a study published in Pediatric Rheumatology.1 Patients without primary response to initial ADA treatment should be switched to an alternative biologic medication rather than further blocking the tumor necrosis factor-alpha (TNF-α) pathway.
“ADA is the first-line biologic choice in refractory JIA-associated uveitis. However, patients in substantial numbers are discontinued ADA treatment for lack of efficacy,” investigators explained. “The options for managing failure of ADA treatment include switching to an alternative anti-TNFα-agent or switching to a drug with a different mode of action. Few data exist for the use of GLM in patients whose uveitis does not respond to ADA.”
Between March 2010 and April 2021, the single-center, retrospective study analyzed the efficacy of patients with JIA being treated with GLM for active uveitis who had non-response to ADA and received at least 1 conventional disease-modifying antirheumatic drug (cDMARD). JIA was determined using the International League of Associations for Rheumatology and uveitis was classified using the Standardization of Uveitis Nomenclature (SUN) Working Group. Clinical data, such as intraocular inflammation, best-corrected visual acuity, corticosteroid-sparing potential, and ocular complications, were evaluated at baseline, 1 month, and 3 months, and continued for every 3 subsequent months during GLM treatment.
Response was defined as complete (CR), partial (PR) or non (NR). Patients achieving CR had inactive uveitis, PR was classified as improved uveitis and decreased inflammation, and NR was defined as no change in SUN score and worsening disease activity.
Patients and their parents also reported any side effects or unusual experiences during GLM treatment.
A total of 10 patients were recruited for the study. Of these, 100% were female, the mean age was 14.3 + 6.7 years and the mean age at onset of JIA was 2.96 + 1.26 years. In 9 patients, the JIA subtype was oligoarthritis, while 1 patient had enthesitis-related arthritis. The most common cDMARDs used were methotrexate (MTX) (n = 10), azathioprine (n = 4), and mycophenolate mofetil (n = 3). At baseline, 80% of patients had ocular complications, including macular edema, cataract, glaucoma, synechiae, and bad keratopathy. More than half (60%) of patients were receiving MTX or azathioprine, 50% of patients were being treated with systemic corticosteroids, and 90% were using topical corticosteroids.
GLM 50 mg was administered subcutaneously every 4 weeks for patients weighing 40 kg or more and 30 mg for those weighing 40 kg or less.
At 1 month, 60% (CR n = 2, PR n = 4) of patients achieved response, 80% (CR n = 4, PR n = 4), at 3 months, 70% (CR n = 3, PR n = 4) at 6 months, 75% (CR n = 5, PR n = 1) at 9 months, 83% (CR n = 4, PR n = 1) at 12 months, and 83% (CR n = 5) at 18 months.
Primary non-response to ADA was seen in 2 patients and 8 received GLM due to LOR, 5 of which had neutralizing anti-ADA-antibodies. Response was seen in all 8 patients with LOR, however, the 2 patients with NR to ADA did not respond to GLM. Those in this subgroup were switched to tocilizumab, an anti-interleukin-6 (IL-6), and achieved CR within 3 months. Median time to treatment failure for patients receiving GLM was 26.8 months.
Additionally, 3 of the 8 patients experienced LOR to GLM throughout treatment. Four of 5 patients were able to reach CR by the end of the study and 1 had achieved PR.
Systemic corticosteroids were reduced from 0.19 mg/kg at baseline to 0.07 mg/kg by 6 months. Further, no patients received systemic corticosteroids between 12 months and 18 months.
The small number of patients examined, due to the rarity of JIA, as well as the retrospective design, limits the study.
“GLM is an effective treatment option in a subset of patients with JIA-associated uveitis,” investigators concluded. “Switching to GLM is more effective in patients with LOR to ADA than in patients without a primary response to ADA. Primary non-responders might instead benefit from switching to a biologic agent with a different mode of action.”
Lanz S, Seidel G, Skrabl-Baumgartner A. Golimumab in juvenile idiopathic arthritis-associated uveitis unresponsive to Adalimumab. Pediatr Rheumatol Online J. 2021;19(1):132. Published 2021 Aug 21. doi:10.1186/s12969-021-00630-1