Long-Term Outcome of Patients With Crohn’s Disease Who Discontinued Infliximab Therapy Upon Clinical Remission

Papamichael, Konstantinos; Casteele, Niels Vande; Gils, Ann; Tops, Sophie; Hauenstein, Scott; Singh, Sharat; Princen, Fred; Assche, Gert Van; Rutgeerts, Paul; Vermeire, Séverine; Ferrante, Marc

doi:10.1016/j.cgh.2014.11.026

Cited by 79 publications

(64 citation statements)

References 27 publications

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“…The most recent retrospective study was from Leuven: the cohort consisted of 100 CD patients who were in clinical remission and stopped biological therapy. The 1-and 2-year cumulative relapse rates were very low: 4 % and 7 %, respectively (23). Even after a median follow-up period of 9.7 years, 52 % of the CD patients in this cohort were still in clinical remission after infl iximab discontinuation.…”

Section: Relapse Rates In Other Studiesmentioning

confidence: 88%

“…Within the fi rst year after stopping, 27 % of the patients in both cohorts relapsed. Other studies reported that the following factors associate with the risk of relapse after infl iximab discontinuation: longer disease duration at the time of fi rst infl iximab infusion (CD patients), previous biological therapy (both CD and UC patients), previous dose intensifi cation (CD patients), and age at the time of diagnosis of less than 25 years (CD patients) (20)(21)(22)(23) .…”

Section: Discussionmentioning

confidence: 99%

“…These include three retrospective and six prospective studies (11)(12)(13)(19)(20)(21)(22)(23)(24). All nine studies included rather few patients (14 to 121), all but two included only infl iximab stoppers, and only three studies included UC patients.…”

Section: Relapse Rates In Other Studiesmentioning

confidence: 99%

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Relapse rates of inflammatory bowel disease patients in deep and clinical remission after discontinuing anti-tumor necrosis factor alpha therapy

Hlavatý¹,

Krajčovičová²,

Letkovsky³

et al. 2016

BLL

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BACKGROUND AND AIMS: Relapse rates after discontinuing anti-tumor necrosis factor-α (TNFα) therapy of infl ammatory bowel disease (IBD) patients in deep remission are poorly understood. This prospective singlecenter open-label study evaluated the relapse rates of IBD patients after stopping anti-TNFα therapy. METHODS: All IBD patients who were in clinical remission and stopped anti-TNFα therapy in 2011-2013 and were followed up for at least 12 months were enrolled. The "Ultradeep" patients were in calprotectin-negative (<50 ng/g) deep remission for at least six months and ceased anti-TNFα therapy on physician recommendations. The "clinical" patients were in clinical but not deep remission and ceased anti-TNFα therapy for other reasons. Relapse rates were assessed and relapse risk factors identifi ed. RESULTS: One year after stopping, 27 % and 27 % of the Ultradeep (n = 11) and Clinical (n = 11) patients relapsed, respectively. Two years after stopping, 57 % and 62 % relapsed, respectively (p = 0.89). All relapsed patients who underwent retreatment with anti-TNFα therap y re-entered remission. Male sex was a signifi cant risk factor for relapse (p = 0.03). CONCLUSION: Our study showed that even highly selected IBD patients who lack clinical, endoscopic or laboratory signs of disease activity have a relatively high relapse rate in the follow-up period after ceasing anti-TNFα therapy (Tab. 2, Fig. 3, Ref. 24). Text in PDF www.elis.sk.

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Section: Relapse Rates In Other Studiesmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Relapse rates of inflammatory bowel disease patients in deep and clinical remission after discontinuing anti-tumor necrosis factor alpha therapy

Hlavatý¹,

Krajčovičová²,

Letkovsky³

et al. 2016

BLL

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“…It is interesting to note that across all adult studies reporting on anti-TNF withdrawal from clinical remission, despite heterogeneous study designs, patient populations, and variable use of immunomodulators, the 1-and 2-year relapse rates were reasonably consistent. 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.…”

Section: De-escalation Of Anti-tnf In CDmentioning

confidence: 89%

“…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. The median time to relapse was between 4.8 and 16.4 months across the studies reporting this outcome.…”

Section: De-escalation Of Anti-tnf In CDmentioning

confidence: 99%

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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Laboratory Evaluation, Including Novel Diagnostic Markers

Flamant

Roblin

2017

Crohn's Disease and Ulcerative Colitis

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Long-Term Outcome of Patients With Crohn’s Disease Who Discontinued Infliximab Therapy Upon Clinical Remission

Cited by 79 publications

References 27 publications

Relapse rates of inflammatory bowel disease patients in deep and clinical remission after discontinuing anti-tumor necrosis factor alpha therapy

Relapse rates of inflammatory bowel disease patients in deep and clinical remission after discontinuing anti-tumor necrosis factor alpha therapy

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

Laboratory Evaluation, Including Novel Diagnostic Markers

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