Secukinumab in HLA‐B27 associated uveitis

Secukinumab is a selective, high affinity, fully-humanised monoclonal antibody against IL17A, a cytokine with a key role in several immunoinflammatory disorders. Secukinumab has been approved by the Food and Drug Administration, U.S. as a 150 mg or 300 mg subcutaneous preparation for the treatment of psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (Ax-SPA). These diseases share many clinical features and an association with HLA-B27. HLA-B27 associated uveitis is an acute, unilateral, recurrent inflammation of the anterior segment of the eye that may occur in association with other HLA-B27 related diseases. Recurrence of HLA-B27 uveitis often involves the fellow eye and can cause complications including synechiae and cataract in milder forms, and retinal vasculitis and macular oedema as more severe manifestations. Most patients respond to short courses of local or oral corticosteroids, but patients with recurrent or severe attacks of HLA-B27 associated uveitis may require long-term treatment with systemic immunosuppressive drugs. Three multicenter, randomised, double-masked, phase III studies (SHIELD, INSURE, ENDURE) found no difference in the number of noninfectious uveitis recurrences when comparing secukinumab to placebo. However, these studies were limited by the potentially confounding effects of concomitant immunosuppressive medications and different types of uveitis enrolled. We describe our experience of using secukinumab in four patients with recurrent HLA-B27 associated uveitis, three of whom had spondyloarthritis (axSpA) and one patient with PsA. The study was approved by the ASST Gaetano Pini-CTO Institute Institutional Review Board (approval n. 138_1999) and conducted under the tenets of the Declaration of Helsinki. Written consent was signed by each participant. Mean age at the time of treatment with secukinumab was 39 years (range: 32-45 years). All patients had an ocular diagnosis of recurrent non-granulomatous anterior uveitis affecting both eyes (Table 1). Mean duration of uveitis was 5 years (range: 3-7 years) with a mean recurrence rate of 4.5 episodes of active uveitis per year (range: 3-6 episodes). Topical corticosteroids were initially effective in controlling intraocular inflammation. However, due to the increase in frequency and severity of uveitis recurrences and the presence of ocular complications (posterior synechiae, cataract, ocular hypertension), patients were started on systemic disease-modifying antirheumatic drugs (DMARDs). All patients were started on adalimumab monotherapy (40 mg fortnightly), and a combination with methotrexate (MTX, 15 mg weekly) was introduced in the patient with PsA. Following adalimumab failure to control uveitis, therapy was switched to infliximab (5 mg/kg every 6 weeks) in combination with MTX for all patients. Improvement in intraocular inflammation was initially documented in all cases, but after a mean time of 2.3 years, patients showed an increasing number of anterior uveitis recurrences. Two patients also experienced arthritis reactivation. In agreement with our rheumatology colleagues, antiIL17A therapy with secukinumab was started at the dosage of 150 mg in axSpA patients and 300 mg in the PsA patient, in combination with MTX 15 mg weekly. Mean follow-up duration of treatment with secukinumab was 12.5 months (range: 9-18 months). Mean uveitis recurrences decreased from 4.2 episodes to 0.9 per year, and intraocular inflammation was controlled without topical corticosteroids. Subcutaneous secukinumab was well tolerated by all patients and no systemic adverse events occurred during follow up. Arthritis was also controlled during follow up under this therapy. IL17A is elevated in the serum and ocular fluids during active uveitis and decreases after effective treatment. Thus, therapies against the IL17A axis are potential targets for noninfectious uveitis. In 2010, Hueber et al reported the efficacy and safety profile of secukinumab on 16 patients with active chronic noninfectious uveitis. However, data from the SHIELD study did not demonstrate efficacy of subcutaneous secukinumab in patients with uveitis. INSURE and ENDURE studies were terminated early, but they did not consider different types of noninfectious uveitis with their different causative molecular pathways. Indeed, not all forms of noninfectious uveitis show dysregulation of IL17A pathways. Despite this, data from SHIELD and INSURE suggested a Received: 23 January 2021 Revised: 15 March 2021 Accepted: 16 March 2021