Withdrawal of Immunomodulators After Co-treatment Does Not Reduce Trough Level of Infliximab in Patients With Crohn’s Disease

Drobne, David; Bossuyt, Peter; Breynaert, Christine; Cattaert, Tom; Casteele, Niels Vande; Compernolle, Griet; Jürgens, Matthias; Ferrante, Marc; Ballet, Vera; Wollants, Willem-Jan; Cleynen, Isabelle; Steen, Kristel Van; Gils, Ann; Rutgeerts, Paul; Vermeire, Séverine; Assche, Gert Van

doi:10.1016/j.cgh.2014.07.027

Cited by 116 publications

(81 citation statements)

References 17 publications

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“…Oussalah et al and Drobne et al reported cumulative relapse rates of 27% and 38% after a median follow-up period of 14 and 29 months, respectively. In the latter study, 29 infliximab levels remained stable after withdrawal of the immunomodulator, although there was an increase in the proportion of those with very low or undetectable infliximab trough levels. An abstract by Fischer et al 31 reported a higher relapse rate (cumulative 72.1% rate of relapse; median time to relapse, 28.1 months) in an observational study.…”

Section: De-escalation Of An Immunomodulator From Combination Therapymentioning

confidence: 92%

“…75 Therapeutic drug monitoring offers a promising avenue to identify candidates for de-escalation. Notably, while higher anti-TNF trough levels at the time of immunomodulator withdrawal were associated with lower rates of relapse, 29 the opposite was true for anti-TNF withdrawal 47,48 In this way, lower trough levels may identify patients in who remission has been achieved irrespective of drug therapy and who would therefore be promising candidates for withdrawal. 76 Studies on re-treatment generally reported good response rates, mostly of clinical remission.…”

Section: Discussionmentioning

confidence: 99%

“…Higher infliximab levels at withdrawal were associated with lower rates of relapse. 29 No studies reported on the response to reintroducing the immunomodulator after relapse. Female sex (P < .02) 55 Lack of maintenance of an IM after discontinuation of anti-TNF (P < .01 ) 55 Epidermal growth factor level ≤39.5 U/mL (HR, 2.7 [1.2-6.6]; sensitivity, 39%; specificity, 86%; PPV, 75%; NPV, 58%) 83 Shorter duration of anti-TNF before cessation 39 IFX trough concentrations <6 µg/mL 48,b Treatment with an IM after discontinuation of anti-TNF: HR, 0.5 (0.3-0.7) 55 Positive serum vascular cell adhesion protein 1 (>0.67 µg/mL) at time of IFX discontinuation 48,b Stopping the IM…”

Section: De-escalation Of An Immunomodulator From Combination Therapymentioning

confidence: 99%

“…These comprised 2 RCTs 26,27 and 6 retrospective cohort studies. [28][29][30][31][32][33] Six studies reported on immunomodulator withdrawal from combination therapy in CD 26,27,[29][30][31][32] and one study in UC 33 ; one study did not differentiate between CD and UC when reporting outcomes.…”

Section: De-escalation Of An Immunomodulator From Combination Therapymentioning

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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Section: De-escalation Of An Immunomodulator From Combination Therapymentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: De-escalation Of An Immunomodulator From Combination Therapymentioning

confidence: 99%

Section: De-escalation Of An Immunomodulator From Combination Therapymentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2015

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“…Supervised elimination of one therapy after 6-12 months was reported. 11,12 Optimising such strategy compared to late immunomodulator addition based on drug level and biomarkers await further clinical testing.…”

mentioning

confidence: 99%