Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn's disease in established remission

Brooks, Alenka J; Sebastian, Shaji; Cross, Simon S.; Robinson, Kerry H.; Warren, Lorraine; Wright, Alison; Marsh, Alexandra; Tsai, Her Hsin; Majeed, Farrukh; McAlindon, ME; Preston, Cathryn; Hamlin, PJ; Lobo, Alan

doi:10.1016/j.crohns.2014.09.007

Cited by 40 publications

(55 citation statements)

References 12 publications

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“…This is, as far as we know, the first randomized trial comparing the long-term outcome of MT with the outcome of ST for ileocaecal CD. Previous studies on the long-term outcome of surgery for ileocaecal CD have shown clinical remission rates of 48%, with only 35% of patients needing a second resection after 10 years, 28 well in line with more recent meta-analyses on immunomodulators and anti-TNF therapies, which showed remission rates of 36 29 -55 30 % after 1 year. Since the initiation of this study, there have also been changes in surgical treatment.…”

Section: Discussionsupporting

confidence: 56%

The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohn’s Disease

Gerdin

Eriksson

Olaison³

et al. 2015

ECCOJC

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Background and aims: The importance of efficient and safe treatment of Crohn's disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohn's disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohn's disease. Methods: Thirty-six patients from seven hospitals with primary ileocaecal Crohn's disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohn's disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints. Results: There were no differences between the treatment groups in Crohn's disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t=erminated prematurely. Conclusion: The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.

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Section: Discussionsupporting

confidence: 56%

The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohn’s Disease

Gerdin

Eriksson

Olaison³

et al. 2015

ECCOJC

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“…One exception is the study by Papamichael et al, 48 which reported the lowest relapse rates after drug discontinuation; the cumulative probability of maintaining sustained clinical remission after the first, second, third, fourth, and fifth year was 96%, 93%, 88%, 79.9%, and 72.8%, respectively. In other studies in which relapse rates were available at 12 and 24 months, 47,[49][50][51][52][53][54][55] the rates ranged from 21.1% to 39% and from 37%% to 55.7%, respectively. Interestingly, except for one study published in abstract form that reported a lower relapse rate of 16% after a mean follow-up of 19 ± 13 months, 56 most studies, including the one by Papamichael et al, reported high cumulative relapse rates of between 49% and 88% by the end of follow-up, 36,37,47,48,52,54,[57][58][59] with higher rates with longer follow-up periods.…”

Section: De-escalation Of Anti-tnf In CDmentioning

confidence: 99%

“…Excluding these studies, remission was safely achieved in a high proportion of patients in all other studies (ranging from 78.3% to 100%). Studies describing longer follow-up remission rates (at least 1 year) reported clinical remission rates between 80% and 92% at 1 year 49,55,64 De-escalation of anti-TNF in UC. Fourteen studies described outcomes after withdrawal of anti-TNF in UC 36,37,52-55,58,59,64,67-71 5 of which were retrospective cohort studies.…”

Section: De-escalation Of Anti-tnf In CDmentioning

confidence: 99%

“…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.…”

Section: De-escalation Of Anti-tnf In CDmentioning

confidence: 99%

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

et al. 2015

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Little is known about the optimal duration of therapy with an anti-tumor necrosis factor (TNF) agent and/or an immunomodulator for patients with inflammatory bowel disease (IBD). We performed a systematic search of the literature to identify studies reporting after de-escalation (drug cessation or dose reduction) of anti-TNF agents and/or immunomodulators in patients in remission from IBD. Studies were reviewed according to the type of IBD and drug. Rates of relapse, factors associated with relapse, and response to re-treatment were determined. Our search yielded 6315 unique citations; we analyzed findings from 69 studies (18 on de-escalation [drug cessation or dose reduction] of immunomodulator monotherapy, 8 on immunomodulator de-escalation from combination therapy, and 43 on de-escalation of anti-TNF agents, including 3 during pregnancy) comprising 4672 patients. Stopping immunomodulator monotherapy after a period of remission was associated with high rates of relapse in patients with Crohn's disease or ulcerative colitis (approximately 75% of patients experienced a relapse within 5 years after therapy was stopped). Most studies of patients with Crohn's disease who discontinued an immunomodulator after combination therapy found that rates of relapse did not differ from those of patients who continued taking the drug (55%-60% had disease relapse 24 months after they stopped taking the immunomodulator). The only study in patients with ulcerative colitis supported continued immunomodulator use. Approximately 50% of patients who discontinued anti-TNF agents after combination therapy maintained remission 24 months later, but the proportion in remission decreased with time. Markers of disease activity, poor prognostic factors, and complicated or relapsing disease course were associated with future relapse. In conclusion, based on a systematic review, 50% or more of patients with IBD who cease therapy have a disease relapse. Further studies are required to accurately identify subgroups of patients who are good candidates for discontinuation of treatment. The decision to withdraw a drug should be made for each individual based on patient preference, disease markers, consequences of relapse, safety, and cost.Keywords : Crohn's Disease ; Ulcerative Colitis ; Patient Management ; Cessation.Abbreviations used in this paper : anti-TNF, anti-tumor necrosis factor therapy ; CD, Crohn's disease ; CRP, C-reactive protein ; FC, fecal calprotectin ; IBD, inflammatory bowel disease ; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses ; RCT, randomized controlled trial ; TNF, tumor necrosis factor ; UC, ulcerative colitis.Therapeutic strategies in inflammatory bowel disease (IBD) have evolved considerably in the past few decades. The acknowledgment that subclinical and undertreated inflammation can lead to poor outcomes has underpinned a shift in treatment goals from symptomatic control to sustained clinical and endoscopic remission.1 Treatment strategies have changed accordingly, including the ear...

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“…The response to restart of TNFα antagonists was effective and well tolerated. Brooks et al [133] observed that relapse rates at 1 year following elective withdrawal of anti-TNFα were 36%. Predictors of relapse included ileocolonic involvement, previous anti-TNFα therapy, and elevated fecal calprotectin.…”

Section: Azathioprine Withdrawal In Patients With Crohn's Diseasementioning

confidence: 98%

Maintenance therapy for Crohn’s disease

Önal

Beyazıt

Altınbaş

et al. 2015

European Journal of Gastroenterology & Hepatology

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Crohn's disease (CD) is a chronic, persistent, and destructive disorder with different forms of clinical behavior and the disease appears to be progressive over the long term. Providing greater levels of mucosal healing and resolution of clinical symptoms may modify the course of CD. This will often necessitate long-term therapy with immunosuppressant or biological therapies. Both these classes of drugs have side-effects and the latter are also very expensive. Identification of a subgroup of patients with a low risk of relapse and validation of the relevant predictors in various cohort studies are the key points to be able to cease immunosuppressant and/or biological therapy in patients with CD in stable remission. The individual parameters 'mucosal healing', 'deep remission', 'fecal calprotectin', and 'C-reactive protein' or various combinations of these parameters seem to be promising tools for predicting successful withdrawal of maintenance therapy.

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Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn's disease in established remission

Cited by 40 publications

References 12 publications

The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohn’s Disease

The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohn’s Disease

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

Maintenance therapy for Crohn’s disease

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