Advertisement

Deep Remission at 1 Year Prevents Progression of Early Crohn’s Disease

      Background & Aims

      We investigated the effects of inducing deep remission in patients with early Crohn’s disease (CD).

      Methods

      We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1–0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05–6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period.

      Results

      Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07–0.31) was significantly associated with a lower risk of major adverse outcome.

      Conclusions

      In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.

      Graphical abstract

      Keywords

      Abbreviations used in this paper:

      aHR (adjusted hazard ratio), anti-TNF (anti–tumor necrosis factor biologics), CALM (Effect of Tight Control Management on Crohn’s Disease), CD (Crohn’s disease), CDAI (Crohn’s disease activity index), CDEIS (Crohn’s Disease Endoscopic Index of Severity), CI (confidence interval), CM (conventional management), HR (hazard ratio), IQR (interquartile range), STRIDE (Selecting Therapeutics Targets in Inflammatory Bowel Disease), TC (tight control)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Torres J.
        • Mehandru S.
        • Colombel J.-F.
        • et al.
        Crohn’s disease.
        Lancet. 2017; 389: 1741-1755
        • Cosnes J.
        • Bourrier A.
        • Nion-Larmurier I.
        • et al.
        Factors affecting outcomes in Crohn’s disease over 15 years.
        Gut. 2012; 61: 1140-1145
        • Malarcher C.A.
        • Wheaton A.G.
        • Liu Y.
        • et al.
        Hospitalizations for Crohn’s disease — United States, 2003–2013.
        MMWR Morb Mortal Wkly Rep. 2017; 66: 377-381
        • Ma C.
        • Moran G.W.
        • Benchimol E.I.
        • et al.
        Surgical rates for Crohn’s disease are decreasing: a population-based time trend analysis and validation study.
        Am J Gastroenterol. 2017; 112: 1840-1848
        • Burisch J.
        • Kiudelis G.
        • Kupcinskas L.
        • et al.
        Natural disease course of Crohn’s disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study.
        Gut. 2019; 68: 423-433
        • Markusse I.M.
        • Akdemir G.
        • Dirven L.
        • et al.
        Long-term outcomes of patients with recent-onset rheumatoid arthritis after 10 years of tight controlled treatment: a randomized trial.
        Ann Intern Med. 2016; 164: 523-531
        • Choy E.H.S.
        • Smith C.M.
        • Farewell V.
        • et al.
        Factorial randomised controlled trial of glucocorticoids and combination disease modifying drugs in early rheumatoid arthritis.
        Ann Rheum Dis. 2008; 67: 656-663
        • Berg D.R.
        • Colombel J.-F.
        • Ungaro R.
        The role of early biologic therapy in inflammatory bowel disease.
        Inflamm Bowel Dis. 2019; 25: 1896-1905
        • Peyrin-Biroulet L.
        • Sandborn W.
        • Sands B.E.
        • et al.
        Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target.
        Am J Gastroenterol. 2015; 110: 1324-1338
        • Colombel J.-F.
        • Panaccione R.
        • Bossuyt P.
        • et al.
        Effect of tight control management on Crohn’s disease (CALM): a multicentre, randomised, controlled phase 3 trial.
        Lancet. 2018; 390: 2779-2789
        • Colombel J.F.
        • Reinisch W.
        • Mantzaris G.J.
        • et al.
        Randomised clinical trial: deep remission in biologic and immunomodulator naïve patients with Crohn’s disease - a SONIC post hoc analysis.
        Aliment Pharmacol Ther. 2015; 41: 734-746
        • Panaccione R.
        • Löfberg R.
        • Rutgeerts P.
        • et al.
        Efficacy and safety of adalimumab by disease duration: analysis of pooled data from Crohn’s disease studies.
        J Crohns Colitis. 2019; 13: 725-734
        • Schreiber S.
        • Colombel J.-F.
        • Bloomfield R.
        • et al.
        Increased response and remission rates in short-duration Crohn’s disease with subcutaneous certolizumab pegol: an analysis of PRECiSE 2 randomized maintenance trial data.
        Am J Gastroenterol. 2010; 105: 1574-1582
        • Rubin D.T.
        • Uluscu O.
        • Sederman R.
        Response to biologic therapy in Crohn’s disease is improved with early treatment: an analysis of health claims data.
        Inflamm Bowel Dis. 2012; 18: 2225-2231
        • Safroneeva E.
        • Vavricka S.R.
        • Fournier N.
        • et al.
        Impact of the early use of immunomodulators or TNF antagonists on bowel damage and surgery in Crohn’s disease.
        Aliment Pharmacol Ther. 2015; 42: 977-989
        • Walters T.D.
        • Kim M.-O.
        • Denson L.A.
        • et al.
        Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn’s disease.
        Gastroenterology. 2014; 146: 383-391
        • Shah S.C.
        • Colombel J.F.
        • Sands B.E.
        • et al.
        Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn’s disease.
        Aliment Pharmacol Ther. 2016; 43: 317-333