Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial
Por:
Perez-Moreiras, JV, Gomez-Reino, JJ, Maneiro, JR, Perez-Pampin, E, Lopez, AR, Alvarez, FMR, Laguarta, JMC, Cabello, AD, Sorroche, MG, Gregori, EE, Sales-Sanz, M
Publicada:
1 nov 2018
Resumen:
OBJECTIVE: To demonstrate the efficacy of the anti-interleukin-6 receptor monoclonal antibody tocilizumab in patients with moderate-to-severe corticosteroid-resis-tant Graves orbitopathy (GO).
DESIGN: Double-masked randomized clinical trial.
METHODS: Setting and Participants: Thirty-two adults with moderate-to-severe corticosteroid-resistant GO from 10 medical centers in Spain were randomized (1:1). Intervention: Randomization to either 8 mg/kg body weight tocilizumab or placebo administered intrave-nously at weeks 0, 4, 8, and 12, and follow-up for an addi-tional 28 weeks. Main Outcomes and Measures: The primary outcome was the proportion of patients with a change from baseline to week 16 of at least 2 in the clin-ical activity score (CAS).
RESULTS: The primary outcome was met by 93.3% (95% confidence interval [CI] 70.1%-98.8%) of the pa-tients receiving tocilizumab and 58.8% (36%-78.3%) receiving placebo (P = .04; odds ratio, 9.8 [CI 1.3-73.2]). A significant difference was also observed in the proportion of patients achieving a CAS < 3 (86.7% [CI 62.1%-96.2%] vs 35.2% [CI 17.3%-58.7%], P = .005; OR 11.9 [CI 2.1-63.1]) at week 16. Additionally, a larger proportion of patients with improvement in the European Group on GO-proposed composite ophthalmic score at week 16 (73.3% [CI 48%-89.1%] vs 29.4% [CI 13.2%53.1%]; P = .03), and exophthalmos size change from baseline to week 16 (-1.5 [-2.0 to 0.5] mm vs 0.0 [-1.0 to 0.5] mm; P = .01) were seen with tocilizumab. One patient experienced a moderate increase in transaminases at week 8; another had an acute pyelonephritis at week 32 in the tocilizumab-treated group.
CONCLUSION: Tocilizumab offers a meaningful improvement in activity and severity in corticosteroid-resistant GO. This trial justifies further studies to characterize the role of tocilizumab in GO. (C) 2018 Elsevier Inc. All rights reserved.
Filiaciones:
Perez-Moreiras, JV:
Inst Int Orbita & Oculoplast, Santiago, Spain
Gomez-Reino, JJ:
Hosp Clin Univ, Fdn Ramon Dominguez, IDIS, Santiago, Spain
Maneiro, JR:
Hosp Clin Univ, Rheumatol Serv, Santiago, Spain
Perez-Pampin, E:
Hosp Clin Univ, Fdn Ramon Dominguez, IDIS, Santiago, Spain
Lopez, AR:
Hosp Clin Madrid, Ophthalmol Serv, Madrid, Spain
Hosp Clin Madrid, Endocrinol Serv, Madrid, Spain
Alvarez, FMR:
Hosp Univ Santa Creu & San Pau, Ophthalmol Serv, Barcelona, Spain
Hosp Univ Santa Creu & San Pau, Endocrinol Serv, Barcelona, Spain
Hosp Univ Santa Creu & San Pau, Rheumatol Serv, Barcelona, Spain
Laguarta, JMC:
Hosp Clin Univ Lozano Blesa, Ophthalmol Serv, Zaragoza, Spain
Hosp Clin Univ Lozano Blesa, Rheumatol Serv, Zaragoza, Spain
Cabello, AD:
Hosp Univ, Ophthalmol Serv, Seville, Spain
Hosp Univ, Endocrinol Serv, Seville, Spain
Hosp Univ, Rheumatol Serv, Seville, Spain
Sorroche, MG:
Hosp Univ Virgen de la Macarena, Ophthalmol Serv, Seville, Spain
Hosp Univ Virgen de la Macarena, Clin Pharmacol Serv, Seville, Spain
Hosp Univ Virgen de la Macarena, Endocrinol Serv, Seville, Spain
Hosp Univ Virgen de la Macarena, Rheumatol Serv, Seville, Spain
Gregori, EE:
Hosp Univ La Fe, Ophthalmol Serv, Valencia, Spain
Hosp Univ La Fe, Endocrinol Serv, Valencia, Spain
Hosp Univ La Fe, Internal Med Serv, Valencia, Spain
Sales-Sanz, M:
Hosp Univ Ramon Y Cajal, Ophthalmol Serv, IRYCIS Crta De Colmenar Km 9,100, Madrid 28034, Spain
Hosp Univ Ramon Y Cajal, Rheumatol Serv, Madrid, Spain
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