Normalization of mucosal cytokine gene expression levels predicts long-term remission after discontinuation of anti-TNF therapy in Crohn's disease

Abstract

Normalization of mucosal gene expression of cytokines after anti-TNF therapy does not occur in all patients with healed mucosa as judged by endoscopy. Normalization of TNF and/or IL17A expression predicts long-term remission.

Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease

“…47 Although it requires further investigation, it is important to acknowledge that recent studies of anti-TNF cessation in patients with deep remission (including some in radiological and even histological remission) have roughly similar relapse rates, with approximately 50% of patients experiencing a relapse after variable periods of follow-up. 39,57,[62][63][64] After stopping therapy, it is possible that an individual's particular disease course will eventually manifest and follow its natural trajectory. 75 Therapeutic drug monitoring offers a promising avenue to identify candidates for de-escalation.…”

“…Radiological healing as assessed by magnetic resonance imaging was also shown in one study. 62 Rismo et al 63 reported higher rates of relapse (52% at 6 months and 74% at 12 months), potentially relating to short treatment duration before withdrawal. The other studies reported relapse rates of 18% at 6 months, 57 22% to 41% at 12 months, 57,62 47% to 49% at 24 months, 57,62 and 50% at 36 months, 39 very similar to that of those withdrawn while in clinical remission.…”

“…47,48 One study looked at molecular healing; elevated expression levels of TNF-α and interleukin-17A in endoscopic healed mucosa were associated with a 3-and 4-fold increased risk of relapse, respectively. 63 Two studies reported on factors predictive of relapse during follow-up rather than at drug discontinuation. 65,66 De Suray et al followed 113 patients in the STORI trial with bimonthly measurements of CRP and FC levels until relapse or 18 months; the investigators found that the evolution of CRP and FC levels was significantly different between those who experienced a relapse and those who did not.…”

“…The median time to relapse was between 4.8 and 16.4 months across the studies reporting this outcome. 38,47,49,53,55,[57][58][59][60][61] Five studies 39,57,[62][63][64] included patients withdrawn from therapy while in both clinical and endoscopic remission. Radiological healing as assessed by magnetic resonance imaging was also shown in one study.…”

Genetic variants associated with Crohn's disease

“…This conclusion comes in part from the findings that CD patients have a higher number of circulating IL-17+ cells33 and from a study by Rismo et al,34 which showed that increased messenger (m) RNA expression of tumor necrosis factor (TNF) and IL17A in healed mucosa significantly increased the risk of relapse (hazard ratio [HR] = 3.4, P = 0.03, sensitivity 80%, specificity 38% and HR = 4.1, P = 0.008, sensitivity 81%, specificity 61%, respectively).…”