Successful treatment of psoriasis-associated uveitis with ixekizumab after failure of secukinumab and risankizumab

Dear Sir, Psoriasis is strongly associated with uveitis, a rare but serious ocular complication. We report a case of psoriasis-associated uveitis treated successfully with ixekizumab, an interleukin (IL)-17A monoclonal antibody, after failure of treatment with secukinumab and risankizumab. A 43-year-old Caucasian woman was seen for follow-up of psoriasis with psoriatic arthritis and uveitis. Skin and joint manifestations were minimal, but she was troubled by left eye painless vision blurring and floaters for 3 months. She had been on treatment with secukinumab for 6 years and was diagnosed with uveitis a year before. Treatment before secukinumab included topical corticosteroids, narrowband ultraviolet B therapy and cyclosporine. Secukinumab was subsequently switched to risankizumab due to residual psoriatic lesions and preference for reduced injection frequency. During her follow-up here, she had been on treatment with risankizumab for 10 months. She was referred to Ophthalmology for uveitis management. Ophthalmic examination found left eye corrected visual acuity of 20/50, mild conjunctival injection, small keratic precipitates, mild anterior chamber cells and flare, and broken posterior synechiae. Posterior segment findings included mild vitritis and disc hyperaemia with moderate macular oedema, confirmed on optical coherence tomography [Figure 1a]. Right eye examination was normal.Figure 1: Optical coherence tomography of the left eye: (a) before ixekizumab therapy (white arrow: macular oedema); and (b) 2 months after ixekizumab therapy, which shows resolution of macular oedema.These findings were consistent with left chronic anterior uveitis complicated by macular oedema. This improved with prednisolone acetate 1% eyedrops; however, tapering in the frequency of eyedrops resulted in uveitis flares. The patient’s nonsteroidal anti-inflammatory drug (NSAID) allergy precluded alternative eyedrops. Due to concern of potential ocular side effects with prolonged corticosteroid eyedrop therapy, risankizumab was switched to ixekizumab 80 mg monthly. After she received two subcutaneous injections of ixekizumab 80 mg over 2 months, there was complete resolution of left eye uveitis and macular oedema [Figure 1b], with improvement in visual acuity to 20/20. Corticosteroid eyedrops was stopped, and she was maintained only on ocular lubricants. Her skin condition remained stable with a psoriasis area and severity index score of 1.2. Psoriasis is a chronic immune-mediated disorder with cutaneous, joint, gastrointestinal and ocular manifestations. Uveitis, though rare in the general population, is estimated to affect 7%–20% of patients with psoriasis.[1] Symptoms include pain, eye redness, floaters and even devastating vision loss. It has been proposed that T-helper cell subsets Th-1 and Th-17 are activated in psoriasis and uveitis. The current standard of care for non-infectious uveitis is topical corticosteroid eyedrops or periocular corticosteroid injection, with cycloplegics. For resistant cases, therapeutic options include systemic corticosteroids or biologics. Among the biologics, anti-tumour necrosis factor agents have shown the most favourable outcomes so far.[2] The cytokine IL-17 has been detected in patients with active uveitis.[2] Ixekizumab prevents binding of IL-17A to the IL-17 receptor, attenuating the proinflammatory cascade causing keratinocyte proliferation and activation in psoriasis. It has shown efficacy in the treatment of plaque psoriasis and ankylosing spondylitis. Clinical trials of ixekizumab in the treatment of psoriasis-associated uveitis have not been registered. With regard to other monoclonal antibodies, there has been reported treatment success of non-infectious uveitis with ustekinumab, an IL-12/IL-23 inhibitor.[3] Secukinumab, another IL-17A inhibitor, has so far failed to demonstrate efficacy for uveitis recurrence over placebo (primary end point)[1] and may warrant higher intravenous doses.[4] Janus kinase inhibitors are another consideration in newer uveitis treatments, with favourable clinical response of ocular inflammation to tofacitinib and baricitinib reported.[5] Our case study demonstrates the potential of ixekizumab in the treatment of psoriasis-associated uveitis. Significant morbidity may be prevented with treatment of the uveitis and from cessation of corticosteroid eyedrops, limiting steroid-associated ocular side effects. With the emergence of anti-interleukin therapy for psoriasis, concurrent treatment of psoriasis and psoriasis-associated uveitis with biologics is promising. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.