Adalimumab in patients with active noninfectious uveitis

Glenn J. Jaffe, Andrew D. Dick, Antoine P. Brézin, Quan Dong Nguyen, Jennifer E. Thorne, Philippe Kestelyn, Talin Barisani-Asenbauer, Pablo Franco, Arnd Heiligenhaus, David Scales, David S. Chu, Anne Camez, Nisha V. Kwatra, Alexandra P. Song, Martina Kron, Samir Tari, Eric B. Suhler

Research output: Contribution to journalArticle

140 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)932-943
Number of pages12
JournalNew England Journal of Medicine
Volume375
Issue number10
DOIs
StatePublished - Sep 8 2016

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Uveitis
Treatment Failure
Placebos
Prednisone
Anterior Chamber
Glucocorticoids
Visual Acuity
Intermediate Uveitis
Panuveitis
Posterior Uveitis
Vision Disorders
Adalimumab
Therapeutics
Research Personnel
Confidence Intervals
Inflammation
Safety
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Jaffe, G. J., Dick, A. D., Brézin, A. P., Nguyen, Q. D., Thorne, J. E., Kestelyn, P., ... Suhler, E. B. (2016). Adalimumab in patients with active noninfectious uveitis. New England Journal of Medicine, 375(10), 932-943. https://doi.org/10.1056/NEJMoa1509852

Adalimumab in patients with active noninfectious uveitis. / Jaffe, Glenn J.; Dick, Andrew D.; Brézin, Antoine P.; Nguyen, Quan Dong; Thorne, Jennifer E.; Kestelyn, Philippe; Barisani-Asenbauer, Talin; Franco, Pablo; Heiligenhaus, Arnd; Scales, David; Chu, David S.; Camez, Anne; Kwatra, Nisha V.; Song, Alexandra P.; Kron, Martina; Tari, Samir; Suhler, Eric B.

In: New England Journal of Medicine, Vol. 375, No. 10, 08.09.2016, p. 932-943.

Research output: Contribution to journalArticle

Jaffe, GJ, Dick, AD, Brézin, AP, Nguyen, QD, Thorne, JE, Kestelyn, P, Barisani-Asenbauer, T, Franco, P, Heiligenhaus, A, Scales, D, Chu, DS, Camez, A, Kwatra, NV, Song, AP, Kron, M, Tari, S & Suhler, EB 2016, 'Adalimumab in patients with active noninfectious uveitis', New England Journal of Medicine, vol. 375, no. 10, pp. 932-943. https://doi.org/10.1056/NEJMoa1509852
Jaffe GJ, Dick AD, Brézin AP, Nguyen QD, Thorne JE, Kestelyn P et al. Adalimumab in patients with active noninfectious uveitis. New England Journal of Medicine. 2016 Sep 8;375(10):932-943. https://doi.org/10.1056/NEJMoa1509852
Jaffe, Glenn J. ; Dick, Andrew D. ; Brézin, Antoine P. ; Nguyen, Quan Dong ; Thorne, Jennifer E. ; Kestelyn, Philippe ; Barisani-Asenbauer, Talin ; Franco, Pablo ; Heiligenhaus, Arnd ; Scales, David ; Chu, David S. ; Camez, Anne ; Kwatra, Nisha V. ; Song, Alexandra P. ; Kron, Martina ; Tari, Samir ; Suhler, Eric B. / Adalimumab in patients with active noninfectious uveitis. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 10. pp. 932-943.
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AU - Jaffe, Glenn J.

AU - Dick, Andrew D.

AU - Brézin, Antoine P.

AU - Nguyen, Quan Dong

AU - Thorne, Jennifer E.

AU - Kestelyn, Philippe

AU - Barisani-Asenbauer, Talin

AU - Franco, Pablo

AU - Heiligenhaus, Arnd

AU - Scales, David

AU - Chu, David S.

AU - Camez, Anne

AU - Kwatra, Nisha V.

AU - Song, Alexandra P.

AU - Kron, Martina

AU - Tari, Samir

AU - Suhler, Eric B.

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N2 - 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.

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