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Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised

Trial and economic evaluation

Key features

• May 2010 - 2013

• 270 patients were recruited to the study

• 52 sites recruited at least one patient to the study

• NIHR Health Technology Assessment

• Chief Investigator: Professor John Williams, Swansea University

• The results showed that ciclosporin is just as effective in treating ulcerative colitis and much cheaper for the NHS.

Ulcerative colitis is a chronic debilitating disease that affects about 150,000 people in the UK. It is a long-term condition, where the colon (large bowel) and rectum become inflamed. Small ulcers can develop on the colon’s lining, and can bleed and produce pus as well as causing recurring diarrhoea and abdominal pain. Acute severe ulcerative colitis (ASC) affects 25 per cent of patients, and requires hospital admission and treatment with intravenous steroids.

About 40 per cent of these patients do not respond to the standard steroid therapy and until 10 years ago colectomy was the only available treatment. Ciclosporin and Infliximab are existing drugs which are used to treat people with ulcerative colitis, both are effective but infliximab is a newer drug and much more expensive than ciclosporin. The CONSTRUCT trial aimed to test their relative clinical effectiveness, measured by quality of life and cost-effectiveness.

Outcomes and findings

The study team conducted a pragmatic randomised trial using mixed quantitative and qualitative methods. 270 participants were recruited to the study from a ‘colitis cohort’ of patients admitted with ASC to hospitals (52 hospitals) across Great Britain. Participants randomised to infliximab received the drug through a drip over two hours, and then received a second and third dose at two and six weeks after the first dose.

Participants randomised to ciclosporin received the drug through a drip which continued for up to seven days if successful, when it was switched to twice-daily oral tablets. After 12 weeks, treatment was at the discretion of the participant’s consultant. For both treatments participants were also able to receive steroid treatment from week four of the study at the discretion of the consultant and asked to discontinue by week 12 in participants who remained well.

The team assessed quality of life through patient-completed questionnaires at the start of the study, three and six months after treatment and then six-monthly for one to three years. A local research professional collated clinical data, laboratory results, drugs, and adverse events, at same time points. The relative cost-effectiveness of the trial drugs was assessed through cost–utility analysis, which estimated differences between groups in NHS costs and quality-adjusted life-years.

The results showed both drugs are just as effective at treating ulcerative colitis and there was no significant difference in the quality adjusted survival of either group of participants. Interviews with participants revealed the substantial impact of ulcerative colitis on their quality of life, and the potential benefits from these medical treatments and from surgery. Participants treated with infliximab generally spoke more positively about the treatment than those treated with ciclosporin.

Value to the NHS

Participants liked infliximab better than ciclosporin, but doctors were more equivocal, whereas nurses disliked the more resource-intensive drip-infusion requirements of ciclosporin. In the primary analysis of the cost-effectiveness of the drugs, at 30 months, total health service costs for ciclosporin (£14,609) were significantly lower than for infliximab (£20,241). By following participants over the next 10 years, through both questionnaires and routine data, we plan to extend our quantitative findings, especially on colectomies and other readmissions.

“This trial was the first in colitis to put patient benefit at the heart of the trial by using quality of life as its primary outcome. This combined with the savings demonstrated to the NHS, make the trial a real success.“

Professor John Williams, Swansea University and Chief Investigator of the study.

Key publications:

• Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open-label, pragmatic randomised trial. The Lancet Gastroenterology & Hepatology 1(1) · June 2016 DOI: 10.1016/S2468-1253(16)30003-6.

• The trial has also been cited in six guideline papers.