Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial.

Abstract

BACKGROUND:

Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little. At present there are no approved therapies for CTD-ILD. Following trials in scleroderma-ILD, cyclophosphamide is the accepted standard of care for individuals with severe or progressive CTD-related ILD. Observational studies have suggested that the anti-CD20 monoclonal antibody, rituximab, is an effective rescue therapy in the treatment of refractory CTD-ILD. However, before now, there have been no randomised controlled trials assessing the efficacy of rituximab in this treatment population.

METHODS/DESIGN:

RECITAL is a UK, multicentre, prospective, randomised, double-blind, double-dummy, controlled trial funded by the Efficacy and Mechanism Evaluation Programme of the Medical Research Council and National Institute for Health Research. The trial will compare rituximab 1 g given intravenously, twice at an interval of 2 weeks, with intravenously administered cyclophosphamide given monthly at a dose of 600 mg/m2 body surface area in individuals with ILD due to systemic sclerosis, idiopathic inflammatory myositis (including anti-synthetase syndrome) or mixed connective tissue disease. A total of 116 individuals will be randomised 1:1 to each of the two treatment arms, with stratification based on underlying CTD, and will be followed for a total of 48 weeks from first dose. The primary endpoint for the study will be change in forced vital capacity (FVC) at 24 weeks. Key secondary endpoints include: safety, change in FVC at 48 weeks as well as survival, change in oxygen requirements, total 48-week corticosteroid exposure and utilisation of health care resources.

DISCUSSION:

This is the first randomised control trial to study the efficacy of rituximab as first-line treatment in CTD-associated ILD. The results generated should provide important information on the treatment of a life-threatening complication affecting a rare group of CTDs.

TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01862926. Registered on 22 May 2013.

• Authors: Peter Saunders, Vicky Tsipouri, Gregory J Keir, Deborah Ashby, Marcus D Flather, Helen Parfrey, Daphne Babalis, Elisabetta A Renzoni, Christopher P Denton, Athol U Wells, Toby M Maher
• Journal: Trials (Trials) Vol. 18 Issue 1 Pg. 275 (06 15 2017) ISSN: 1745-6215 [Electronic] England
• PMID: 28619061 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Immunosuppressive Agents
• Rituximab
• Cyclophosphamide

Topics

• Administration, Intravenous
• Adrenal Cortex Hormones (administration & dosage)
• Clinical Protocols
• Connective Tissue Diseases (diagnosis, drug therapy, immunology, physiopathology)
• Cyclophosphamide (administration & dosage, adverse effects)
• Double-Blind Method
• Drug Administration Schedule
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects)
• Lung (drug effects, immunology, physiopathology)
• Lung Diseases, Interstitial (diagnosis, drug therapy, immunology, physiopathology)
• Oxygen Inhalation Therapy
• Prospective Studies
• Recovery of Function
• Research Design
• Rituximab (administration & dosage, adverse effects)
• Time Factors
• Treatment Outcome
• United Kingdom
• Vital Capacity