Editorial: To Stop Or Not To Stop: Is It Still A Question?

Abstract

Treatment approaches for inflammatory bowel disease (IBD) have changed considerably within the last two decades. Biological agents and small molecules have dramatically lifted the therapeutic ceiling. The treat-to-target concept is increasingly implemented with the latest STRIDE-II guidelines summarising the key goals as symptomatic response and remission, normalisation of C-reactive protein and decrease of faecal calprotectin and mucosal healing [1]. The latter has been associated with improved long-term outcome [2]. Even the formerly utopian goal of disease clearance might be achieved in a subset of patients.

The availability of efficacious drugs and the concept of mucosal healing, has led to a shift from a step-up to a top-down therapeutic strategy. In fact, early initiation of aggressive treatment has been shown to be more effective [3]. This now raises the question of whether medications can be stopped or at least reduced once mucosal healing is achieved. Such treatment reduction includes complete withdrawal of a treatment, de-escalation or de-intensification. A simpler question is whether co-medications can be stopped once biologics or small molecules are started.

Seo et al. have tried to answer this question by examining a large nationwide cohort in South Korea [4]. The authors found—based on 7442 patients—that stopping 5-aminosalicylic acid (5-ASA) was not associated with an inferior outcome over a 4.3-year follow-up. Importantly, their analyses were corrected for confounders such as age, sex, disease duration, comorbidities and insurance status. The authors concluded that discontinuing 5-ASA after initiation of anti-TNF agents is safe given the absence of an increased risk of adverse events.

This is an important step for the concept of treatment reduction. Previous studies have shown that 5-ASA withdrawal is safe in the short-term [5]. With a follow-up period > 4 years, this study closes the gap with regards to longer term outcome. Assuming a price of 157.45€/months, rigorous 5-ASA withdrawal in the treatment group would have resulted in an estimated €52 million savings. In the current era of economic pressure, this is considerable, even when considering the study period of 13 years. Low-cost medications have an economic impact when prescribed to large numbers of patients. Nevertheless, the study has one important limitation. It is almost impossible to assess the previously described chemopreventive effect of 5-ASA [6] over only 4 years. The incidence of IBD-associated colorectal cancer (CRC) has dramatically decreased in recent years. In the latest studies, a hazard ratio of 1.66 compared to the general population was found [7]. Still, uncontrolled disease is a significant risk factor for the development of CRC over time [8]. Whether 5-ASA has a value in chemoprevention in otherwise well controlled patients remains debatable, but should be at least investigated prospectively. If this would be the case, the cost saving calculations would get a whole new meaning, because CRC prevention would justify a certain price to pay. 5-ASA: To stop or not to stop? It is still a question, but less so than in the past.

Stephan R. Vavricka: conceptualization, writing – original draft, writing – review and editing. Thomas Greuter: conceptualization, writing – original draft.

S.R.V. has received consulting fees and unrestricted research grants from Abbott, Falk Pharma GmbH, Ferring Pharmaceuticals, Janssen, MSD, Pfizer Inc., Sanofi-Aventis, Takeda, Tillotts, UCB and Vifor. T.G. has consulting contracts with Sanofi-Regeneron, Bristol-Myers Squibb, Takeda, Abbvie, Janssen, Eli Lilly, Pfizer and Dr. Falk Pharma GmbH, received travel grants from Dr. Falk Pharma GmbH and Vifor, speaker's fee from Norgine and Amgen, and an unrestricted research grant from Novartis.

This article is linked to Seo et al papers. To view these articles, visit https://doi.org/10.1111/apt.18102 and https://doi.org/10.1111/apt.18341.