Glenn J Jaffe1, Andrew D Dick1, Antoine P Brézin1, Quan Dong Nguyen1, Jennifer E Thorne1, Philippe Kestelyn1, Talin Barisani-Asenbauer1, Pablo Franco1, Arnd Heiligenhaus1, David Scales1, David S Chu1, Anne Camez1, Nisha V Kwatra1, Alexandra P Song1, Martina Kron1, Samir Tari1, Eric B Suhler1. 1. From Duke University, Durham, NC (G.J.J.); University of Bristol, Bristol Eye Hospital, Bristol, and National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London - both in the United Kingdom (A.D.D.); Université Paris Descartes, Hôpital Cochin, Paris (A.P.B.); Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha (Q.D.N.); Johns Hopkins Medical Institute, Baltimore (J.E.T.); Ghent University Hospital, Ghent, Belgium (P.K.); Laura Bassi Center of Expertise Ocuvac, Medical University of Vienna, Vienna (T.B.-A.); Organización Médica de Investigación, Buenos Aires (P.F.); the Department of Ophthalmology, St. Franziskus-Hospital Münster, Münster (A.H.), University of Duisburg-Essen, Essen (A.H.), and AbbVie Deutschland, Ludwigshafen (A.C., M.K.) - all in Germany; University of Texas Health Science Center, San Antonio (D.S.); Metropolitan Eye Research and Surgery Institute, Palisades Park, NJ (D.S.C.); AbbVie, North Chicago, IL (N.V.K., A.P.S., S.T.); and Casey Eye Institute, Oregon Health and Science University, and VA Portland Health Care System (E.B.S.) - both in Portland.
Abstract
BACKGROUND:Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).
RCT Entities:
BACKGROUND:Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).
Authors: Esperanza Pato; Mª Auxiliadora Martin-Martinez; Adela Castelló; Rosalía Méndez-Fernandez; Santiago Muñoz-Fernández; Miguel Cordero-Coma; Lucia Martinez-Costa; Elia Valls; Miguel Reyes; Félix Francisco; Mar Esteban; Alex Fonollosa; Fernando Sanchez-Alonso; Cruz Fernández-Espartero; Teresa Diaz-Valle; José Miguel Carrasco; Emma Beltran-Catalán; Marisa Hernández-Garfella; María Victoria Hernández; Laura Pelegrin; Ricardo Blanco; David Diaz-Valle Journal: Rheumatol Int Date: 2016-11-04 Impact factor: 2.631
Authors: Mathilde Leclercq; M Le Besnerais; V Langlois; N Girszyn; Y Benhamou; C Ngo; H Levesque; M Muraine; J Gueudry Journal: Clin Rheumatol Date: 2018-02-03 Impact factor: 2.980
Authors: Courtney McCracken; Steven Yeh; Kirsten Jenkins; Curtis Travers; Daneka Stryker; Steven Tommasello; Kelly A Rouster-Stevens; Scott R Lambert; Sampath Prahalad; Carolyn Drews-Botsch; Sheila T Angeles-Han Journal: Eye (Lond) Date: 2018-11-28 Impact factor: 3.775