Long-term efficacy and tolerability of TNFα inhibitors in the treatment of non-infectious ocular inflammation:an 8-year prospective surveillance study

BACKGROUND/AIM: To report the efficacy and tolerability of antitumour necrosis factor-alpha therapy (TNF inhibitors [TNFi]) in the management of non-infectious ocular inflammation, including uveitis and scleritis, in adult patients over an 8-year period. MATERIALS AND METHODS: This is a prospective cohort study of infliximab and adalimumab in the treatment of non-infectious ocular inflammatory disease. 43 of 85 adult patients on TNFi (34 infliximab, 9 adalimumab) for ≥1 year with non-infectious uveitis or scleritis were followed from 2006 to 2014. Clinical assessments, medication, adverse events and history of steroid rescues were collected at 6 monthly intervals. General quality of life (Short Form Health Survey (SF-36)) and visual quality of life (Vision-related quality of life Core Measure (VCM1)) were assessed annually. Outcome measures included rate of sustained remission, rate of relapse, systemic corticosteroid reduction, adverse events, and VCM1 and SF-36 scores. RESULTS: The median time on infliximab was 3.2 years (IQR 4.3) and on adalimumab was 2.4 years (IQR 1.8). Sustained remission was induced in 39 patients (91%) (0.5 per patient year) after a median of 1.2 years on a TNFi. 22 (51%) experienced one relapse, and 5 (12%) had two relapses. 23 (54%) had at least one adverse event; serious adverse events necessitating hospitalisation or cessation of medication occurred in four (9%) patients. 10 patients (23%) switched from the initiation of TNFi, at 1.7 years after starting, to another TNFi or another class of biologic therapy. CONCLUSION: TNFi treatment is associated with long-term drug-induced remission of ocular inflammation, visual stability and corticosteroid reduction. Adverse events were common and no new safety signals occurred. Relapse of inflammation occurs in half of the treated population

Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness-a protocol for a randomised controlled trial (ASTUTE trial).

IntroductionAdalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care.Methods and analysisThe ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted.Ethics and disseminationThe trial received Research Ethics Committee (REC) approval from South Central - Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available.Trial registrationISRCTN31474800. Registered 14 April 2020

A Review of the Landscape of Targeted Immunomodulatory Therapies for Non-Infectious Uveitis

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>.</b> <a href="https://link.springer.com/article/10.1007/s40123-017-0115-5">https://link.springer.com/article/10.1007/s40123-017-0115-5</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

Systemic corticosteroid use in UK Uveitis practice: results from the ocular inflammation steroid toxicity risk (OSTRICH) study.

OBJECTIVES To ascertain adherence to an international consensus target of ≤7.5 mg/day of prednisolone for maintenance systemic corticosteroid (CS) prescribing in uveitis and report the frequency of courses of high-dose systemic CS in the UK. METHODS We conducted a national, multicentre audit of systemic CS prescribing for uveitis at 11 UK sites between November 2018 and March 2019. High-dose CS was defined as (1) maintenance >7.5 mg prednisolone for >3 consecutive months, or (2) >1 course ≥40 mg oral CS or ≥500 mg intravenous (IV) methylprednisolone in the past 12 months. Case notes of patients exceeding threshold CS doses were reviewed by an independent uveitis specialist and judged as avoidable or not, based upon a scoring matrix. RESULTS Of 667 eligible patients, 285 (42.7%) were treated with oral or IV CS over the preceding 12 months; 96 (33.7%) of these exceeded the threshold for high-dose CS. Twenty-five percent of prescribing in patients on excess CS was judged avoidable; attributed to either prescribing long-term CS without evidence of consideration of alternative strategies, prescribing error or miscommunication. More patients received immunomodulatory therapy (IMT) in the group treated with CS above threshold than below threshold (p < 0.001) but there was no significant difference in doses of IMT. CONCLUSION 33% of patients had been prescribed excessive corticosteroid when compared to the reference standard. An analysis of decision-making suggests there may be opportunity to reduce excess CS prescribing in 25% of these patients