Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial

Louis, Édouard; Resche‐Rigon, Matthieu; Laharie, David; Satsangi, Jack; Ding, Nik S.; Siegmund, Britta; D’Haens, Geert; Picon, Laurence; Bossuyt, Peter; Vuitton, Lucine; Irving, Peter M.; Viennot, Stéphanie; Lamb, Christopher A.; Pollok, Richard; Baert, Filip; Nachury, Maria; Fumery, Mathurin; Gilletta, Cyrielle; Almér, Sven; Ben‐Horin, Shomron; Bouhnik, Yoram; Colombel, Jean–Frédéric; Hertervig, Erik

doi:10.1016/s2468-1253(22)00385-5

Cited by 47 publications

(15 citation statements)

References 30 publications

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“…The SPARE trial (2015–2021) sought to evaluate three treatment approaches for Crohn's disease patients in steroid-free remission due to combined infliximab and immunosuppressant therapy: maintaining the combination, continuing only the immunosuppressant, or continuing only infliximab. 32 We include here a subgroup of patients from the SPARE trial who had been randomised to infliximab withdrawal and had a baseline serum aliquot available for analysis ( n = 63).…”

Section: Methodsmentioning

confidence: 99%

Sodium fluoride preserves blood metabolite integrity for biomarker discovery in large-scale, multi-site metabolomics investigations

Xiong,

Anthony,

Anthony

et al. 2024

Analyst

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Section: Methodsmentioning

confidence: 99%

Sodium fluoride preserves blood metabolite integrity for biomarker discovery in large-scale, multi-site metabolomics investigations

Xiong,

Anthony,

Anthony

et al. 2024

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“…In patients who discontinued infliximab, only a 6-TGN at baseline higher than 300 pmol per 8 × 10 8 red blood cells was associated with relapse. 360 In a 10-year follow-up study including UC patients with moderate to severe disease, it has been demonstrated that mucosal TNF copies/µg mRNA < 10,000 at anti-TNF discontinuation predicted long-term remission, biological free remission and lower risk of colectomy. 361 Another study showed that it was possible to identify IBD patients who appeared quiescent but were not in histological remission and who were, consequently, at risk of relapse using serum samples multiomics approach.…”

Section: Timing For Treatment De-escalation or Discontinuation And Id...mentioning

confidence: 99%

“…359 The SPARE study, a multicentre, open-label, randomized controlled trial performed in 64 hospitals in 7 countries in Europe and Australia also studied the factors associated with time to relapse. 360 Adult CD patients in steroid-free clinical remission for more than 6 months, on combination therapy of infliximab and immunosuppressant therapy for 34 journals.sagepub.com/home/tag TherapeuTic advances in Gastroenterology at least 8 months were randomly assigned (1:1:1) to continue combination therapy (combination group), discontinue infliximab (infliximab withdrawal group) or discontinue immunosuppressant therapy (immunosuppressant withdrawal group). 360 Factors associated with time to relapse were as follows: infliximab withdrawal group (versus the combination group and versus the immunosuppressant withdrawal group), young age at diagnosis (<17 years), hsCRP at baseline (1.0 mg/l of hsCRP inducing a 0.1 increment of HR), faecal calprotectin higher than 300 μg/g at baseline, Crohn's Disease Endoscopic Index of Severity (CDEIS) at baseline (1.0 point of CDEIS inducing a 0.1 increment of hazard ratio or HR).…”

Section: Therapeutic Advances In Gastroenterologymentioning

confidence: 99%

“… 360 Adult CD patients in steroid-free clinical remission for more than 6 months, on combination therapy of infliximab and immunosuppressant therapy for at least 8 months were randomly assigned (1:1:1) to continue combination therapy (combination group), discontinue infliximab (infliximab withdrawal group) or discontinue immunosuppressant therapy (immunosuppressant withdrawal group). 360 Factors associated with time to relapse were as follows: infliximab withdrawal group ( versus the combination group and versus the immunosuppressant withdrawal group), young age at diagnosis (<17 years), hsCRP at baseline (1.0 mg/l of hsCRP inducing a 0.1 increment of HR), faecal calprotectin higher than 300 μg/g at baseline, Crohn’s Disease Endoscopic Index of Severity (CDEIS) at baseline (1.0 point of CDEIS inducing a 0.1 increment of hazard ratio or HR). In patients who discontinued infliximab, only a 6-TGN at baseline higher than 300 pmol per 8 × 10 8 red blood cells was associated with relapse.…”

Section: Timing For Treatment De-escalation or Discontinuation And Id...mentioning

confidence: 99%

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Precision medicine and drug optimization in adult inflammatory bowel disease patients

Vieujean

Louis

2023

Therap Adv Gastroenterol

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Inflammatory bowel diseases (IBD) encompass two main entities including ulcerative colitis and Crohn’s disease. Although having a common global pathophysiological mechanism, IBD patients are characterized by a significant interindividual heterogeneity and may differ by their disease type, disease locations, disease behaviours, disease manifestations, disease course as well as treatment needs. Indeed, although the therapeutic armamentarium for these diseases has expanded rapidly in recent years, a proportion of patients remains with a suboptimal response to medical treatment due to primary non-response, secondary loss of response or intolerance to currently available drugs. Identifying, prior to treatment initiation, which patients are likely to respond to a specific drug would improve the disease management, avoid unnecessary side effects and reduce the healthcare expenses. Precision medicine classifies individuals into subpopulations according to clinical and molecular characteristics with the objective to tailor preventative and therapeutic interventions to the characteristics of each patient. Interventions would thus be performed only on those who will benefit, sparing side effects and expense for those who will not. This review aims to summarize clinical factors, biomarkers (genetic, transcriptomic, proteomic, metabolic, radiomic or from the microbiota) and tools that could predict disease progression to guide towards a step-up or top-down strategy. Predictive factors of response or non-response to treatment will then be reviewed, followed by a discussion about the optimal dose of drug required for patients. The time at which these treatments should be administered (or rather can be stopped in case of a deep remission or in the aftermath of a surgery) will also be addressed. IBD remain biologically complex, with multifactorial etiopathology, clinical heterogeneity as well as temporal and therapeutic variabilities, which makes precision medicine especially challenging in this area. Although applied for many years in oncology, it remains an unmet medical need in IBD.

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“…10 Some studies have a focused biologic discontinuation for patients with CD due to clinical or endoscopic remission such as the recent STOP-IT (Discontinuation of Infliximab Therapy in Patients With Crohn's Disease During Sustained Complete Remission) and the SPARE trial (Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy) to Anti-Metabolites Monotherapy and Infliximab Monotherapy in Crohn's Disease Patients in Sustained Steroid-Free Remission on Combination Therapy) trials. [22][23][24][25] However, due to the high cost of biologics, according to the reimbursement criteria of our NHI program, patients with CD can only be reimbursed for a limited number of doses of biologic agents. After these doses, regardless of whether disease remission is achieved, these patients are required to discontinue biologic treatment.…”

Section: Articlementioning

confidence: 99%

Suboptimal Outcomes and Retreatment Rate of Patients With Crohn's Disease After Forced Discontinuation of Biologics: A Nationwide Population‐Based Study

Chen

Chuang

Chang

et al. 2023

Clin Pharma and Therapeutics

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Taiwan's National Health Insurance programme forced discontinuation of biologic use in Crohn's disease after a limited treatment duration, regardless of disease activity. This study investigated the retreatment rate and suboptimal outcomes [i.e., Crohn's disease–related surgeries, hospitalisations, emergency room visits and oral steroid flare‐ups] after forced discontinuation. This retrospective cohort study was conducted using data from the National Health Insurance Database. Patients who received ≥40 weeks of biologic treatment followed by a forced discontinuation were included. The time of biologic retreatment and the cumulative incidence of suboptimal outcomes after the forced discontinuation as well as related risk factors were analyzed. 215 patients were included [68% male]. At the beginning of biologic therapy, the mean age [±SD] was 35.7 [±13.5] years, and the disease duration was 4.46 [±3.52] years. The median [interquartile range] biologic treatment duration was 57.86 [50.3–83.3] weeks. Within the first year after forced discontinuation, 67% of patients [n = 144] were retreated with a second course of biologics, and 53% of patients [n = 114] experienced at least one suboptimal outcome. The independent risk factors associated with the occurrence of suboptimal outcomes were Crohn's disease–related emergency room visits and hospitalisations during biologic therapy [hazard ratio: 2.49; 95% CI: 1.59–3.89]. More than two‐thirds of CD patients required biological retreatment within 1 year after a forced discontinuation. The substantial proportion of patients with poor disease outcomes highlights the need to continue the biologic.

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Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial

Cited by 47 publications

References 30 publications

Sodium fluoride preserves blood metabolite integrity for biomarker discovery in large-scale, multi-site metabolomics investigations

Sodium fluoride preserves blood metabolite integrity for biomarker discovery in large-scale, multi-site metabolomics investigations

Precision medicine and drug optimization in adult inflammatory bowel disease patients

Suboptimal Outcomes and Retreatment Rate of Patients With Crohn's Disease After Forced Discontinuation of Biologics: A Nationwide Population‐Based Study

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