Posted on April 15, 2026

Appendectomy as an Adjunct in Refractory Ulcerative Colitis: Chop It Off When Everything Else Fails!

Vasantham Chaudhary, MD1 and Elie Al Kazzi, MD, MPH2

1Fellow Physician, Division of Gastroenterology & Hepatology, NYU Langone Health, New York, NY

2Assistant Professor of Medicine, NYU Grossman School of Medicine, New York, NY

This article reviews Visser E, Reijntjes MA, Heuthorst L, et al. Appendicectomy versus switching to a JAK inhibitor in inducing remission in patients with active ulcerative colitis after biologic therapy failure (COSTA): 1-year results of a multicentre, prospective, cohort study. Lancet Gastroenterol Hepatol. 2026 Mar;11(3):190-203.

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Correspondence to Elie S. Al Kazzi, MD, MPH, Associate Editor Email: EBGI@gi.org

Keywords: appendectomy, JAK inhibitor, ulcerative colitis, refractory

STRUCTURED ABSTRACT

Question: In patients with moderate to severe ulcerative colitis (UC) with advanced therapy failure, does laparoscopic appendectomy as an adjunct to advanced therapy induce clinical remission more effectively than switching to a Janus kinase (JAK) inhibitor?

Design: Multicenter, patient-preference, controlled interventional cohort study.

Setting: Five hospitals in the Netherlands.

Patients: Patients ≥16 years old with moderately to severely active UC (total Mayo score [TMS] of 5-12, and endoscopic subscore of 2 or higher) despite treatment with advanced therapy. Patients were excluded if prior appendectomy, suspected Crohn’s disease, toxic megacolon, acute severe UC, or colonic dysplasia/malignancy. Patients were ineligible for appendectomy if requiring >20mg daily prednisone.

Interventions/Exposure: Patients were counseled on 3 treatment options during an outpatient visit: 1) laparoscopic appendectomy with continuation of existing advanced therapy, 2) switch from existing biologic to JAK inhibitor, 3) colectomy.

Outcomes: Primary outcome was proportion of patients at 12 months in clinical remission (TMS ≤2, with no individual subscore >1 point) without therapy failure (start or restart of oral steroids, switch to a different advanced therapy, start of clinical trial, or colectomy).

Secondary outcomes included corticosteroid-free clinical remission, clinical response (≥2-point TMS reduction and ≥30% decrease from baseline), endoscopic improvement (subscore ≤1), endoscopic response (≥1-point subscore decrease), time to symptomatic remission, therapy failure rate, and colectomy rate within 12 months.

Data Analysis: Modified intention-to-treat (ITT) population. Binary outcomes between appendectomy and JAK inhibitor group compared using Fisher’s exact test and Pearson chi-squared test. Time-to-first symptomatic remission analyzed by Kaplan-Maier with log rank test and Cox proportional hazards model. Missing primary outcome data treated as treatment failure.

Funding: Funded by ZonMW.

Results: A total of 125 patients were enrolled and 116 included in modified ITT analysis: 67 undergoing appendectomy and 49 with JAK inhibitor. Baseline characteristics between appendectomy and JAK inhibitor arm were overall similar, with median age 39 vs 42 years, 37% vs 53% male, median disease duration 6.6 vs 7.8 years, and 43% vs 59% pancolitis. The appendectomy arm had lower rates of baseline corticosteroid use (27% vs 45%, p = 0.044), and greater anti-TNF use at baseline (48% vs 27%, P= 0.02). The JAK inhibitor group received tofacitinib (84%), filgotinib (12%), or upadacitinib (4%). Five patients opted for colectomy, who had longer disease duration of 8.9 years, more previous exacerbations, with 80% baseline corticosteroid use.

Clinical remission without therapy failure at 12 months was achieved in 32.8% of appendectomy group compared with 12.2% of JAK inhibitor group (P = 0.01). Clinical response at 12 months was higher in the appendectomy arm (73% vs 53%, P= 0.025), as were endoscopic improvement (55% s. 33%, P= 0.016), and endoscopic response (48% vs 26%, P= 0.018) at 12 months.

Therapy failure rates were similar between groups (58% vs 57%, P= 0.91), as were 12-month colectomy rates (9% vs 8%, P= 1.0). Time to symptomatic remission was similar: HR 1.06 (95% CI 0.62 – 1.82, P= 0.82). Surgical complication rates occurred in 4% of appendectomy arm, and all were minor. Baseline corticosteroid use was an independent predictor of lower clinical remission rates (OR 0.27, 95% CI 0.08 – 0.95, P = 0.042).

Table 1. Comparison of results for primary and secondary outcomes for appendectomy vs a Janus kinase (JAK) inhibitor.

COMMENTARY

Why Is This Important?
Previously thought to be a vestigial organ, the appendix is increasingly thought to serve an important role in mucosal immunity and colonic microbiome stability. It contains abundant gut-associated lymphoid tissue (GALT), including IgA producing plasma cells and CD4 T cells.1,2 Appendectomy may modulate colonic inflammation by shifting towards a more immunoprotective state, though mechanisms are incompletely understood.

Prior evidence of appendectomy includes a small study by Bolin and colleagues in 2009 on 30 patients with ulcerative proctitis, showing 90% with improvement and 40% with complete resolution over a median 14-month follow-up.3 The PASSION pilot study enrolled 30 refractory patients who had been referred for colectomy, finding 30% with lasting clinical response, and long-term follow-up showing one quarter with endoscopic improvement at 8 years.4,5 Most recently, the ACCURE trial randomized 197 patients with UC in remission to appendectomy plus standard therapy vs standard therapy alone, showing a lower 1-year relapse rate (36% vs 56%).1 In contrast to ACCURE, the COSTA study involved patients with active disease and higher advanced therapy exposure rates. Together, they suggest that appendectomy may be considered as a potential adjunct to medical therapy in select patients with ulcerative colitis.

Key Study Findings

Appendectomy as an adjunct to ongoing advanced therapy achieved clinical remission without therapy failure in 33% of patients at 12 months, compared with 12% with JAK inhibitor therapy alone in patients with moderately to severely active UC.

All secondary efficacy endpoints favored appendectomy, including clinical response (73% vs 53%), endoscopic improvement (55% vs 33%), and endoscopic response (48% vs 26%) at 12 months. Despite higher remission rates, therapy failure and colectomy rates (8-9%) remained similar between groups at 12 months. Appendectomy was safe with a surgical complication rate of 4% (all minor).

Caution
The major limitations are the non-randomized (patient-preference) design, and small sample size. The predominant use of tofacitinib in the JAK inhibitor arm is another limitation, as the preferred induction agent in the United States is now upadacitinib (only used in 2 patients in this study). The difference in clinical remission rates may have been attenuated with greater upadacitinib use.

My Practice
The COSTA trial adds data to an increasing body of evidence supporting the role of appendectomy as an adjunctive treatment in UC. Appendectomy is planned to be included in the upcoming ECCO UC guidelines for therapy-refractory UC (particularly for younger patients with proctitis or left-sided colitis). This may be an interesting option for patients with moderate to severe disease who wish to limit their risk of needing colectomy or who are averse to ongoing immunosuppression. However, the same patients may also be hesitant about risks of surgery with appendectomy, even if laparoscopic and with low complication rates. Counseling patients in remission about prophylactic appendectomy, as suggested in the ACCURE trial, is challenging for similar reasons. Patients who feel well are often reluctant to pursue elective surgery, and it is difficult for us to confidently recommend this approach without larger studies.

As upadacitinib is our preferred JAK inhibitor in refractory UC across both outpatient and inpatient settings, we are particularly curious whether the remission gap observed in COSTA would persist.

For Future Research
Future research should identify predictors of response from appendectomy, including histologic and endoscopic features such as the presence of a cecal patch, to help guide patient selection. Studies should also compare against more effective therapies like upadacitinib or combination advanced therapy which is increasingly being used in our practice. Ultimately, larger trials with longer follow-up are needed for us to move appendectomy from an intriguing adjunctive option to something we can recommend with confidence.

Conflict of Interest
Drs. Chaudhary and Al Kazzi report no potential conflicts of interest related to this study.

Note
The authors of this study are active on social media. Tag them to discuss their work and this EBGI summary.
@Vasantham_A

REFERENCES 

  1. ACCURE Study Group. 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. Lancet Gastroenterol Hepatol. 2025;10(6):550-561.
  2. Agrawal M, Allin KH, Mehandru S, Faith J, Jess T, Colombel JF. The appendix and ulcerative colitis – an unsolved connection. Nat Rev Gastroenterol Hepatol. 2023;20(9):615-624.
  3. Bolin TD, Wong S, Crouch R, Engelman JL, Riordan SM. Appendicectomy as a therapy for ulcerative proctitis. Am J Gastroenterol. 2009 Oct;104(10):2476-82.
  4. Sahami S, Wildenberg ME, Koens L, et al. Appendectomy for therapy-refractory ulcerative colitis results in pathological improvement of colonic inflammation: Short-term results of the PASSION Study. J Crohns Colitis. 2019;13(2):165-171.
  5. Reijntjes MA, Heuthorst L, Stellingwerf ME, D’Haens GR, Bemelman WA, Buskens CJ. Long-term outcomes after appendicectomy as experimental treatment for patients with therapy-refractory ulcerative colitis. Br J Surg. 2024;111(1):znad425.

 
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