Tag Archives: relapse

ACCURE Trial: Appendectomy As an Adjunct Ulcerative Colitis Treatment Plus One

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YIZ Acherman, et al. The Lancet Gastroenterology & Hepatology, 2025. DOI: 10.1016/S2468-1253(25)00026-3. Open access! Appendicectomy plus standard medical therapy versus standard medical therapy alone for maintenance of remission in ulcerative colitis (ACCURE): a pragmatic, open-label, international, randomised trial

Background: “An inverse association between appendicectomy and the development of ulcerative colitis was first reported in 1987, with subsequent case-control studies confirming this observation, and suggesting a possible role of the appendix in ulcerative colitis. In 2016, our research group did a systematic review and meta-analysis of available (case-control) studies. This analysis showed that previous appendicectomy was associated with a significantly reduced risk of developing ulcerative colitis, with an overall odds ratio of 0·39 (95% CI 0·29–0·52).”

Methods:  Adult patients (n=197) with established ulcerative colitis who were in remission but had been treated for disease relapse within the preceding 12 months were randomly assigned (1:1) to undergo appendicectomy plus continued maintenance medical therapy (intervention group) or to continue maintenance medical therapy alone (control group). Approximately 25% of participants had pancolitis.

Key findings:

  • The 1-year relapse rate was significantly lower in the appendicectomy group than in the control group (36 [36%] of 99 patients vs 55 [56%] of 98 patients; relative risk 0·65 [p=0·005; adjusted p=0·002). 
Relapse Rate

My take (borrowed from the authors): “The ACCURE trial is the first randomised controlled trial evaluating the clinical effectiveness of appendicectomy in maintaining remission in patients with ulcerative colitis without advanced medical therapy (ie, biologicals or small molecules). This trial shows that laparoscopic appendicectomy, in addition to standard medical therapy, significantly reduces the relapse rates within 1 year.”

Also, NPR notes 5/5/25: NIH cuts baby ‘Safe to Sleep’ team. Here’s what parents should know

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Lingering Histologic Changes with Eosinophilic Esophagitis in Remission, Plus One

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A recent study (KA Whelan et al. Clin Gastroenterol Hepatol 2020; 18: 1475-82) examined esophageal histology in 243 patients (mean age 16.9 years) in 3 groups: active eosinophilic esophagitis (EoE), inactive EoE (<15 eos/hpf), and a control non-EoE group.

Key findings:

Basal cell hyperplasia and spongiosis were present in 43 (29%) and 109 (74%) respectively of patients with inactive EoE. In comparison, these findings were present in 98% and 100% respectively of those with active EoE and in 6% and 33% of non-EoE patients

My take: This study provides some insight into the idea that esophageal damage may be ongoing in the absence of eosinophils.  These histologic findings could provide part of the reasons for symptoms in those who have had resolution of esophageal eosinophilia.

Related study: ES Dellon et al. Clin Gastroenterol Hepatol 2020; 18: 1483-92. This study showed rapid recurrence of eosinophilic esophagitis after discontinuation of topical steroids.  33/58  (57%) had symptom recurrence before 1 year (median time 244 for symptoms). At time of symptom recurrence, 78% had histologic relapse (≥15 eos/hpf).

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High Risk of Relapse in Younger Patients after anti-TNF Therapy Withdrawal

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From KT Park’s Twitter Feed:

Article first published online: 19 FEB 2016

NA Kennedy et al.  Aliment Pharm Ther; 2016. DOI: 10.1111/apt.13547

Abstract:

Background

Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months’ anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation.

Aim

To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis.

Methods

A retrospective observational study was performed on 166 patients with IBD (146 with Crohn’s disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC).

Results

Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 × 109/L) and faecal calprotectin (HR 2.95 for >50 μg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta-analysis, estimated 1-year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU.

Conclusions

Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission.

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El Junque, Puerto Rico

El Junque, Puerto Rico

Not Using and Stopping Therapy in IBD

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Two recent articles show that a lot of patients are not receiving much therapy in inflammatory bowel disease.

  • Moreno-Rincon E et al. Inflamm Bowel Dis 2015; 21: 1564-71.
  • Melesse DY et al. Inflamm Bowel Dis 2015; 21: 1615-22.

In the first article, a multicenter retrospective study of 102 patients, the authors examined the relapse rates of patients with ulcerative colitis who had withdrawal of thiopurines.  They defined “significant clinical relapse” (SCR) as “the occurrence of UC typical signs or symptoms requiring a rescue therapy such as oral or intravenous corticosteroids, biological therapy, immunosuppressant drugs, recapture with TP [thiopurine] or surgery.”

Key findings:

  • Overall SCR was 32.35%.
  • Predictors of relapse included pancolitis (HR 5.01) and duration of treatment with thiopurines (HR 0.15).

Among those without relapse, the mean duration of remission prior to withdrawal of thiopurines was 54 months compared with 34 months in those who relapsed. In figure 2, the authors note that the rate of relapse was 19.2% for those who received >48 months of thiopurine treatment compared with a 45% rate of relapse for those who received treatment for 13-47 months.  The authors note that several studies have shown higher relapse rates than reported in this cohort and that interruption of therapy is associated with a considerable risk of relapse.

Limitations: small retrospective study and the expectation that their SCR would capture the true relapse rate.

The second study, using a Manitoba database, shows a strikingly-high rate of nonuse of medical therapy. Between 1996-2012, 3902 patients with IBD were identified; 47% with Crohn’s disease (CD) and 53% with ulcerative colitis (UC).  While only 11.7% of IBD patients did not have medication dispensed in the first year after diagnosis, beyond this period, “roughly half of all patients with IBD have not used IBD-specific medications in the previous year.”  The authors are not certain how much nonuse is due to nonadherence or nonprescription. They note that there was higher nonuse in patients with CD, possibly due to use of surgical treatment.  However, they note that multiple medications have been shown to reduce postsurgical relapse in CD.

My take: There are a lot of patients off therapy, both due to withdrawal of therapy when doing well and others due to nonadherence or nonprescription.  With or without overt symptoms, these studies make one wonder whether undertreatment will lead to long-term complications or whether there could be a significant number of patients who are overtreated.  Either way, it remains quite difficult to predict which patients will do well off medical therapy.

Broadcasters Really Know the Key Points to Winning!

Broadcasters Really Know the Key Points to Winning!