• Biologics … To continue or not after one year of treatment?

    “Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis.”

    Kennedy NA et al. Aliment Pharmacol Ther 2016; 43: 910−923.

     

    Summary

    Biologics play an important role in the treatment of IBD. However, they are expensive and there are concerns over long-term safety. Serious potential side effects include infections, malignancies (including skin cancer), and immune-regulated conditions. Once remission has been achieved on maintenance anti-TNF therapy, clinicians, patients and financers may all have different motivations for a trial of drug withdrawal. In the UK, the National Institute for Clinical Excellence (NICE) and the Scottish Medicines Consortium (SMC) recommend reassessment at 12-monthly intervals with a consideration for drug cessation where patients are in stable remission. There is presently insufficient data on relapse rates following treatment cessation.

    The scientists in this paper examined the rate of disease relapse in IBD patients after anti-TNF withdrawal using new data from a large UK cohort. They carried out a large retrospective observational study on 166 adult patients with IBD from 21 centres in the UK (with a total of 146 patients with Crohn’s disease (CD) and 20 with Ulcerative colitis (UC) and IBD-Unclassified (IBD-U)). All patients were withdrawn from anti-TNF therapy for sustained clinical remission, and were assessed for possible predictive factors for relapse and the success of drug reintroduction.

    80% of CD patients and 95% of UC/IBDU patients were on infliximab prior to withdrawal; the remainder were on adalimumab. Median treatment time prior to withdrawal was 29 months for CD and 21 months for UC/IBDU. Relapse rates were 36% by one year and 56% by two years for CD, and 42% by one year and 47% by two years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis, white cell count and faecal calprotectin at drug withdrawal. There was no significant difference in relapse rates between CD and UC/IBDU. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU.

    In conclusion, this study shows that approximately one in three patients with any form of IBD are likely to experience a moderate-to-severe flare within 12 months of anti-TNF withdrawal, and one in two by 24 months. Just under half of all patients who relapsed required steroids; hospital admission rates were relatively low (17% in CD, 0% in UC); and surgery was rare (two patients).

    This study provides us with relevant data on the risk and safety of withdrawing anti-TNF therapy in patients who achieve sustained remission. It also adds useful information in relation to the efficacy of restarting anti-TNF therapy. Identification of reliable predictors of relapse at withdrawal would be pivotal to stratify the risk and make individualised decisions: i.e. withdrawal for patients with no risk/low risk of relapse, and continuation for the ones at high risk of relapse. In this regard, research focused on developing prognostic biomarkers for disease relapse remains one of the current goals in IBD research.

    MG