Utilisation of composite endpoint outcome to assess efficacy of tocilizumab for non-infectious uveitis in the STOP-Uveitis Study.


Journal

The British journal of ophthalmology
ISSN: 1468-2079
Titre abrégé: Br J Ophthalmol
Pays: England
ID NLM: 0421041

Informations de publication

Date de publication:
08 2023
Historique:
received: 12 10 2021
accepted: 18 03 2022
medline: 24 7 2023
pubmed: 6 4 2022
entrez: 5 4 2022
Statut: ppublish

Résumé

To use a composite endpoint scoring system in assessing efficacy of two doses of intravenous tocilizumab (TCZ), in eyes with non-infectious uveitis. Data from STOP-Uveitis Study (a phase 2 multicentre, randomised, interventional clinical trial), where monthly intravenous infusions of 4 mg/kg (Group 1) or 8 mg/kg (Group 2) TCZ until month 6 (M6) were administered, were used. Efficacy was ascertained by a composite endpoint scoring system consisting of: (1) visual acuity; (2) intraocular inflammation; (3) central retinal thickness; (4) posterior segment inflammation on fluorescein angiographic and (5) steroid taper. Each component of grading system was graded as ((+1) improvement, (-1) worsening or (0) no change) based on specific criteria. The clinical response was classified as positive (improvement in at least one parameter and worsening in none), negative (worsening of any parameter) or stable (neither improvement nor worsening of any parameter). The percentage achieving various clinical responses was compared between groups. Thirty-seven patients were analysed. At M6, 31 (83.8%) subjects demonstrated a positive clinical response (Group 1=14 (77.8%) and Group 2=17 (89.5%)). Three (8.1%) subjects (all Group 1) met the criteria for treatment failure, whereas three (8.1%) subjects showed a stable clinical response (Group 1=1 and Group 2=2). The difference in clinical responses between study groups was not significant (p>0.05). Both doses of intravenous TCZ were effective in either improving or maintaining stability in patients using the composite endpoint scoring system. A composite scoring system as used in this study may be a better measure to assess efficacy outcomes as compared with only vitreous haze or other single outcome measures.

Sections du résumé

BACKGROUND/AIMS
To use a composite endpoint scoring system in assessing efficacy of two doses of intravenous tocilizumab (TCZ), in eyes with non-infectious uveitis.
METHODS
Data from STOP-Uveitis Study (a phase 2 multicentre, randomised, interventional clinical trial), where monthly intravenous infusions of 4 mg/kg (Group 1) or 8 mg/kg (Group 2) TCZ until month 6 (M6) were administered, were used. Efficacy was ascertained by a composite endpoint scoring system consisting of: (1) visual acuity; (2) intraocular inflammation; (3) central retinal thickness; (4) posterior segment inflammation on fluorescein angiographic and (5) steroid taper. Each component of grading system was graded as ((+1) improvement, (-1) worsening or (0) no change) based on specific criteria. The clinical response was classified as positive (improvement in at least one parameter and worsening in none), negative (worsening of any parameter) or stable (neither improvement nor worsening of any parameter). The percentage achieving various clinical responses was compared between groups.
RESULTS
Thirty-seven patients were analysed. At M6, 31 (83.8%) subjects demonstrated a positive clinical response (Group 1=14 (77.8%) and Group 2=17 (89.5%)). Three (8.1%) subjects (all Group 1) met the criteria for treatment failure, whereas three (8.1%) subjects showed a stable clinical response (Group 1=1 and Group 2=2). The difference in clinical responses between study groups was not significant (p>0.05).
CONCLUSIONS
Both doses of intravenous TCZ were effective in either improving or maintaining stability in patients using the composite endpoint scoring system. A composite scoring system as used in this study may be a better measure to assess efficacy outcomes as compared with only vitreous haze or other single outcome measures.

Identifiants

pubmed: 35379598
pii: bjophthalmol-2021-320604
doi: 10.1136/bjophthalmol-2021-320604
doi:

Substances chimiques

tocilizumab I031V2H011

Types de publication

Randomized Controlled Trial Multicenter Study Clinical Trial, Phase II Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1197-1201

Subventions

Organisme : NEI NIH HHS
ID : P30 EY026877
Pays : United States

Informations de copyright

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: YJS has received research support from Astellas, Genentech and Optovue, and serves on the Scientific Advisory Board for Genentech/Roche, Optos and Regeneron. QDN serves on the Scientific Advisory Board for AbbVie, Bayer, Genentech, Regeneron and Santen, among others, also chaired the Steering Committee for the STOP-Uveitis study and was on the Steering Committee for other studies sponsored by Genentech and Regeneron. DVD serves on the Scientific Advisory Board for Allergan, Genentech, Kodiak, Regeneron and Santen and has received research support from Genentech and Regeneron. No other authors have received any financial funding or support.

Auteurs

Muhammad Hassan (M)

Byers Eye Institute, Stanford University, Stanford, California, USA.

Mohammad Ali Sadiq (MA)

Department of Ophthalmology, Weill Cornell Medicine, New York, New York, USA.

Maria Soledad Ormaechea (MS)

Byers Eye Institute, Stanford University, Stanford, California, USA.
Department of Ophthalmology, Hospital Universitario Austral, Pilar, Argentina.

Günay Uludağ (G)

Byers Eye Institute, Stanford University, Stanford, California, USA.

Muhammad Sohail Halim (MS)

Byers Eye Institute, Stanford University, Stanford, California, USA.

Rubbia Afridi (R)

Byers Eye Institute, Stanford University, Stanford, California, USA.

Diana V Do (DV)

Byers Eye Institute, Stanford University, Stanford, California, USA.

Yasir Jamal Sepah (YJ)

Byers Eye Institute, Stanford University, Stanford, California, USA.

Quan Dong Nguyen (QD)

Byers Eye Institute, Stanford University, Stanford, California, USA ndquan@stanford.edu.

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Classifications MeSH