Discontinuation of Infliximab Therapy in Patients with Crohn’s Disease

Buhl, Sine; Steenholdt, Casper; Brynskov, Jørn; Christensen, Katrine Risager; Dorn-Rasmussen, Maria; Thomsen, Ole Østergaard; Bendtzen, Klaus; Klausen, Tobias Wirenfeldt; Dahlerup, Jens Frederik; Thorsgaard, Niels; Jahnsen, Jørgen; Molazahi, Akbar; Pedersen, Natalia; Kjeldsen, Jens; Almér, Sven; Dahl, Eva Efsen; Vind, Ida; Cannon, Annett Gerhardt; Marsal, Jan; Sipponen, Taina; Agnholt, Jørgen; Kievit, Hendrika Adriana Linda; Aure, Synnøve Louise; Martinsen, L.; Meisner, Svetlana; Hansen, Jane Møller; Ainsworth, Mark

doi:10.1056/evidoa2200061

Cited by 18 publications

(17 citation statements)

References 23 publications

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“…Although the study did not reveal any significant risk factors for relapse after IFX withdrawal, concomitant IM at discontinuation demonstrated a tendency to decrease the risk of relapse. The result of the reintroduction of IFX was not assessed in this study [ 14 ].…”

Section: Discontinuation Of Tnfimentioning

confidence: 99%

“…Notably, the true disadvantage of withdrawal should not be recognized by the relapse rate after discontinuation itself but by the increase of relapse rate over relapse rate with continued therapy, because a considerable number of patients may still relapse even if the therapy is continued (Fig. 1 ) [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Evidence-Based Approach to the Discontinuation of Immunomodulators or Biologics in Inflammatory Bowel Disease

Miyatani

2022

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Background: Biologics and immunomodulators are key drugs in the long-term treatment of inflammatory bowel diseases, while they may negatively impact patients’ quality of life due to concerns of adverse events, need for frequent hospital visits, and medical expenses. The basic concept of drug withdrawal should be based on the risk of relapse and the efficacy of re-treatment. Considering a number of patients may relapse even if treatment is continued, the disadvantage of discontinuation should be recognized not by all relapse after discontinuation, but by the increase in relapse. Summary: Discontinuation of immunomodulator monotherapy is associated with an increased risk of relapse. However, prolonged remission might be an indication of withdrawal, concerning the long-term adverse effect including lymphoma and nonmelanoma skin cancers. When considering discontinuation from combination therapy of anti-tumor necrosis factor (TNF) agents with immunomodulators, therapeutic drug monitoring may be useful to understand the pharmacokinetic effect. However, recent randomized controlled trials, as well as large-scale observational studies, demonstrated that discontinuation of anti-TNF agents, but not of immunomodulators, resulted in a significantly higher risk of relapse even in deep remission. Therefore, discontinuation of anti-TNF agents should be considered with caution and close monitoring combined with fecal calprotectin may be necessary. On the other hand, evidence of not only short-term relapse rate but of the true long-term influence on the patient’s quality of life should be clarified by a multidimensional approach. Key Messages: Discontinuation of treatment should be implemented based on shared decision-making with careful interpretation of evidence and the condition.

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Section: Discontinuation Of Tnfimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evidence-Based Approach to the Discontinuation of Immunomodulators or Biologics in Inflammatory Bowel Disease

Miyatani

2022

Digestion

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“…38 In contrast, a recent RCT analyzing infliximab discon-tinuation in CD showed a considerably higher risk of clinical relapse in the placebo group after 48 weeks, regardless of deeper remission at baseline (relapse-free survival: 51% vs 100%). 39 In addition, a recent large-scale retrospective observational study of 1,000 IBD patients who discontinued infliximab or adalimumab demonstrated that 12% of patients relapsed annually, and the cumulative relapse rate at years was 48% after discontinuation. 40…”

Section: Anti-tnf-α 1) Discontinuation Of Tnfimentioning

confidence: 99%

“…In a recent RCT that assessed the effectiveness of infliximab discontinuation in UC and CD with mucosal healing or transmural healing, there were significant differences between the placebo and continued groups regarding the rate of relapse. These findings suggest that achieving a more stringent target alone may not prevent future relapse following de-escalation; 38,39 therefore, it is necessary to assess whether disease control depends on the current medication.…”

Section: Assessment Of Risk Factors For Relapse 1 Understanding the D...mentioning

confidence: 99%

De-escalation of Therapy in Patients with Quiescent Inflammatory Bowel Disease

Miyatani

2022

Gut and Liver

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Inflammatory bowel disease is a chronic disease of unknown origin that requires long-term treatment. The optical duration of maintenance treatment once remission has been achieved remains unclear. When discussing a de-escalation strategy, not only the likelihood of relapse but also, the outcome of retreatment for relapse after de-escalation should be considered. Previous evidence has demonstrated controversial results for risk factors for relapse after de-escalation due to the various definitions of remission and relapse. In fact, endoscopic or histologic remission has been suggested as a treatment target; however, it might not always be indicative of a successful drug withdrawal. For better risk stratification of relapse after de-escalation, it may be necessary to evaluate both the current and previous treatments. Following de-escalation, biomarkers should be closely monitored. In addition to the risk of relapse, a comprehensive understanding of the overall outcome, such as the long-term safety, patient quality of life, and impact on healthcare costs, is necessary. Therefore, a shared decision-making with patients on a case-by-case basis is imperative.

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“…However, the precise endpoint of biologics administration and whether remission can be maintained without treatment remain a matter of debate. Even after deep remission, clinical cases of relapse in patients who discontinued biologics have been reported, with a large number of the relapsed patients having to restart treatment ( 10 , 11 ). In fact, one study suggested that combined clinical and endoscopic remission should not be an impetus to consider therapeutic de-escalation ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Increased monocyte abundance as a marker for relapse after discontinuation of biologics in inflammatory bowel disease with deep remission

Kwon

Kim²,

Choe³

et al. 2022

Front. Immunol.

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Monocytes are involved in the upstream inflammatory process in the immune reaction in inflammatory bowel disease (IBD). Patients with IBD who discontinued biologics have been found to relapse, even after checking for deep remission. This study investigated whether monocytes could act as a predictor of relapse in patients who experienced relapse after the discontinuation of biologics. To this end, pediatric patients (<19 years old, n = 727) diagnosed with IBD from January 2003 to December 2021 were retrospectively reviewed. Clinical features, monocytes, and disease activity at the time of discontinuing biologics were evaluated by dividing patients into a relapsed group and a non-relapsed group after discontinuing biologics. The percentage of monocytes (8.65% vs. 6.42%, P < 0.001), the absolute monocyte count (614.79 cells/μL vs. 381.70 cells/μL, P < 0.001), and the monocyte/polymorphonuclear leukocyte (PMN) ratio (0.18 vs. 0.11, P < 0.001) at the time of discontinuation were significantly higher in patients who experienced relapse. As a result of multivariate analysis, the monocyte percentage (odds ratio: 2.012, P < 0.001) and monocyte/PMN ratio (odds ratio: 4.320E+14, P = 0.002) were evaluated as risk factors for relapse. Diagnostic capability was confirmed using area under operating characteristic curve (0.782) of the monocyte percentage for assessing the relapse within 6 months with cutoff value of 8.15% (P < 0.001). The findings presented in this study indicate that the patients with high monocyte counts experienced relapse after the discontinuation of biologics. A monocyte percentage of over 8.15% in the blood at the time of discontinuation was found to be associated with a high probability of relapse within 6 months, even in deep remission.

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Discontinuation of Infliximab Therapy in Patients with Crohn’s Disease

Cited by 18 publications

References 23 publications

Evidence-Based Approach to the Discontinuation of Immunomodulators or Biologics in Inflammatory Bowel Disease

Evidence-Based Approach to the Discontinuation of Immunomodulators or Biologics in Inflammatory Bowel Disease

De-escalation of Therapy in Patients with Quiescent Inflammatory Bowel Disease

Increased monocyte abundance as a marker for relapse after discontinuation of biologics in inflammatory bowel disease with deep remission

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