Jose V Perez-Moreiras1, Juan J Gomez-Reino2, Jose R Maneiro3, Eva Perez-Pampin2, Angel Romo Lopez4, Fernando M Rodríguez Alvarez5, Jesús M Castillo Laguarta6, Aurora Del Estad Cabello7, María Gessa Sorroche8, Enrique España Gregori9, Marco Sales-Sanz10. 1. Instituto Internacional de Orbita y Oculoplastica, Santiago, Spain. 2. Fundación Ramon Dominguez, IDIS, Hospital Clinico Universitario, Santiago, Spain. 3. Rheumatology Service, Hospital Clinico Universitario, Santiago, Spain. 4. Ophthalmology and Endocrinology Services, Hospital Clínico, Madrid, Spain. 5. Ophthalmology, Endocrinology, and Rheumatology Services, Hospital Universitario de la Santa Creu i San Pau, Barcelona, Spain. 6. Ophthalmology and Rheumatology Services, Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain. 7. Ophthalmology, Endocrinology, and Rheumatology Services, Hospital Universitario, Virgen de Rocio, Sevilla, Spain. 8. Ophthalmology, Clinical Pharmacology, Endocrinology, and Rheumatology Services, Hospital Universitario Virgen de la Macarena, Sevilla, Spain. 9. Ophthalmology, Endocrinology, and Internal Medicine Services, Hospital Universitario La Fe, Valencia, Spain. 10. Ophthalmology and Rheumatology Services, Hospital Universitario Ramon y Cajal, Madrid, Spain. Electronic address: salessanz@yahoo.es.
Abstract
OBJECTIVE: To demonstrate the efficacy of the anti-interleukin-6 receptor monoclonal antibody tocilizumab in patients with moderate-to-severe corticosteroid-resistant 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 intravenously at weeks 0, 4, 8, and 12, and follow-up for an additional 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 clinical activity score (CAS). RESULTS: The primary outcome was met by 93.3% (95% confidence interval [CI] 70.1%-98.8%) of the patients 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.
RCT Entities:
OBJECTIVE: To demonstrate the efficacy of the anti-interleukin-6 receptor monoclonal antibody tocilizumab in patients with moderate-to-severe corticosteroid-resistant 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 intravenously at weeks 0, 4, 8, and 12, and follow-up for an additional 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 clinical activity score (CAS). RESULTS: The primary outcome was met by 93.3% (95% confidence interval [CI] 70.1%-98.8%) of the patients 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.
Authors: Peter N Taylor; Lei Zhang; George J Kahaly; Marian Ludgate; Richard W J Lee; Ilaria Muller; Daniel G Ezra; Colin M Dayan Journal: Nat Rev Endocrinol Date: 2019-12-30 Impact factor: 43.330