Infliximab as a bridge to remission maintained by antimetabolite therapy in Crohn's disease: A retrospective study

Chauvin, Armelle; Thuaut, Aurélie Le; Belhassan, Mehdi; Baleur, Yann Le; Mesli, Farida; Bastuji‐Garin, Sylvie; Delchier, Jean Charles; Amiot, Aurélien

doi:10.1016/j.dld.2014.04.012

Cited by 33 publications

(56 citation statements)

References 22 publications

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“…Additional predictors for maintaining clinical remission during an anti‐TNF drug holiday should also be considered in deciding suitability for an anti‐TNF drug holiday. These include the absence of recent corticosteroid use, no prior bowel resections, nonsmoking status, female gender, haemoglobin >145 g/L, endoscopic mucosal healing and normalisation of inflammatory biomarkers (white cell count, CRP and faecal calprotectin) . Given that the consequences of disease relapse are high in patients with aggressive disease phenotypes (such as following multiple surgeries, prior disease refractory to multiple therapeutic classes), the decision to undertake a drug holiday must be carefully considered and individualised.…”

Section: Resultsmentioning

confidence: 99%

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Mitrev¹,

Casteele

Seow³

et al. 2017

Aliment Pharmacol Ther

242

207

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Summary Background Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti‐tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. Aim To develop evidence‐based consensus statements for TDM‐guided anti‐TNF therapy in IBD. Methods A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. Results 22/24 statements met criteria for consensus. For anti‐TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3‐8 and 5‐12 μg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints—such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision‐making. In stable clinical response, TDM‐guided dosing may avoid future relapse. Data indicate drug‐tolerant anti‐drug antibody assays do not offer an advantage over drug‐sensitive assays. Further data are required prior to recommending TDM for non‐anti‐TNF biological agents. Conclusion Consensus statements support the role of TDM in optimising anti‐TNF agents to treat IBD, especially in situations of treatment failure.

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Section: Resultsmentioning

confidence: 99%

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Mitrev¹,

Casteele

Seow³

et al. 2017

Aliment Pharmacol Ther

242

207

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“…14 A French retrospective cohort comparing the outcome of CD patients after IFX withdrawal using induction alone or induction plus at least 1-year of maintenance therapy found that 72% of patients relapsed after a median follow-up of 47 months in both groups. 16 A retrospective study from Leuven 17 reported the lowest rates of CD relapse after IFX discontinuation while in clinical remission with 96%, 93% and 52%…”

Section: Discussionmentioning

confidence: 99%

Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn’s Disease in Sustained Remission

Reenaers

Mary

Nachury

et al. 2018

Clinical Gastroenterology and Hepatology

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“…A study in a pediatric population found high relapse rates of 75% and 73% in the induction and maintenance groups, respectively, after 1 year. 42 The other 2 studies 40,41 reported relapse rates of 22% to 29% (induction group) and 31% to 44% (maintenance group) after 1 year; the difference between the groups was not statistically significant. Molnar et al found a similar relapse rate of 45% in a study of withdrawal after 3 induction doses of infliximab.…”

Section: De-escalation Of Anti-tnf In CDmentioning

confidence: 99%

“…47 On the other hand, another study found previous antimetabolite failure to be predictive of relapse. 41 Higher infliximab trough levels at withdrawal was associated with relapse in 2 studies. 47,48 One study looked at molecular healing; elevated expression levels of TNF-α and interleukin-17A in endoscopic healed mucosa were associated with a 3-and 4-fold increased risk of relapse, respectively.…”

Section: De-escalation Of Anti-tnf In CDmentioning

confidence: 99%

“…35 In 6 studies, the proportion of patients on a concomitant immunomodulator was not specified 34,[36][37][38][39] ; in the remaining studies, it ranged from 20 to 100%. Three studies [40][41][42] compared relapse rates after infliximab withdrawal after induction alone ("induction group") with relapse rates after withdrawal after at least 1 year of scheduled maintenance therapy ("maintenance group"). There were no significant differences in the rates of relapse between the induction and maintenance groups in each study, although the actual rates of relapse varied between studies.…”

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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Infliximab as a bridge to remission maintained by antimetabolite therapy in Crohn's disease: A retrospective study

Cited by 33 publications

References 22 publications

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn’s Disease in Sustained Remission

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

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