Withdrawal of thiopurines in Crohn’s disease treated with scheduled adalimumab maintenance: a prospective randomised clinical trial (DIAMOND2)

Hisamatsu, Tadakazu; Kato, Shingo; Kunisaki, Reiko; Matsuura, Minoru; Nagahori, Masakazu; Motoya, Satoshi; Esaki, Motohiro; Fukata, Norimasa; Inoue, Satoko; Sugaya, Takeshi; Sakuraba, Hirotake; Hirai, Fumihito; Watanabe, Kenji; Kanai, Takanori; Naganuma, Makoto; Nakase, Hiroshi; Suzuki, Yasuo; Watanabe, Mamoru; Hibi, Toshifumi; Nojima, Masanori; Matsumoto, Takayuki

doi:10.1007/s00535-019-01582-w

Cited by 23 publications

(24 citation statements)

References 26 publications

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“…Endoscopic healing, defined by the absence of mucosal ulcers, was also similar in both groups (16 [64%] of 25 in the continuation group vs 14 [61%] of 23 in the discontinuation group), although combination therapy was associated with lower concentrations of C-reactive protein (CRP). 29 A further open-label RCT, DIAMOND2, 34 assessed thiopurine withdrawal from the treatment regimen of patients in steroid-free clinical remission for at least 6 months following combination therapy with adalimumab. Preliminary results report no difference in the primary endpoint of steroid-free remission at 52 weeks, or in a secondary endpoint of mucosal healing, suggesting no clear benefit in continuation of immunomodulators beyond 6 months of clinical remission.…”

Section: Withdrawal Of the Immunomodulator From Combination Therapymentioning

confidence: 99%

“…However, only a small number of patients (n=50) were included, and the thiopurine dose was much lower than that commonly used in Europe. 34 A subsequent systematic review has analysed relapse rates following immunomodulator (azathioprine) discontinuation from combination therapy in Crohn's disease. Overall, 27 (49%) of 55 patients relapsed after immunomodulator withdrawal compared with 27 (48%) of the 56 patients who continued immunomodulators (RR 1.02 [0.68-1.52]; p=0.92).…”

Section: Withdrawal Of the Immunomodulator From Combination Therapymentioning

confidence: 99%

“…39 A further study reported that combination therapy resulted in a longer drug antibody free survival. 40 The effect of immunomodulators on adalimumab trough concentrations is less clear, with the DIAMOND2 study 34 reporting no difference at week 52 when the immunomodulator was discontinued after at least 6 months of combination therapy. Finally, results from the PANTS study 35 have shown that concurrent immunomodulator use reduces the risk of immunogenicity for both infliximab (hazard ratio [HR] 0.39; p<0.0001) and adalimumab (HR 0.44; p<0.0001).…”

Section: The Effect Of Immunomodulators Withdrawal On the Immunogenicmentioning

confidence: 99%

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De-escalation of immunomodulator and biological therapy in inflammatory bowel disease

Chapman

Gomes

Louis

et al. 2020

The Lancet Gastroenterology & Hepatology

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Treatment strategies for inflammatory bowel disease (IBD) focus on the induction and longterm maintenance of deep remission to avoid complications of active disease and improve longterm outcomes. Medical therapies for IBD, notably the increasingly widespread use of biological therapy, are often effective at controlling disease, but these drugs are associated with substantial adverse events, which together with other factors-including increasing treatment costs and patient preferences-leads to concerns regarding indefinite use of medical therapy. Consequently, the need to consider the safety and feasibility of drug de-escalation once IBD remission has been achieved is clear. Here, we review the current evidence surrounding deescalation of immunomodulator and biological therapy in Crohn's disease and ulcerative colitis. We discuss strategies for de-escalation, including the selection of patients who are appropriate for treatment de-escalation and the use of proactive drug monitoring, and review the evidence on subsequent optimal follow-up. We conclude by proposing an algorithm to guide de-escalation decisions, and highlight future perspectives, including the potential effect of emerging medication and personalised medicine for these diseases.

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Section: Withdrawal Of the Immunomodulator From Combination Therapymentioning

confidence: 99%

Section: Withdrawal Of the Immunomodulator From Combination Therapymentioning

confidence: 99%

Section: The Effect Of Immunomodulators Withdrawal On the Immunogenicmentioning

confidence: 99%

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De-escalation of immunomodulator and biological therapy in inflammatory bowel disease

Chapman

Gomes

Louis

et al. 2020

The Lancet Gastroenterology & Hepatology

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“…Studies reported data from Europe (n = 12), America (n = 2), Africa (n = 1) and Asia (n = 4). Patients with CD were studied in 13 studies [17][18][19][20][21][22][23][24]27,29,[40][41][42] and patients with UC in 4 studies, 25,26,39,43 and 2 studies recruited both CD and UC population. 44,45 Clinical relapse was determined in 14 [17][18][19][20][21][22][23]25,26,[40][41][42][43][44] and RCT 1…”

Section: Characteristics Of the Studies Includedmentioning

confidence: 99%

“…25,26 In three RCTs, IM withdrawal in CD patients treated in combination with biologic therapy resulted in a similar relapse rate compared to that of continued combination therapy. [27][28][29] In a recent meta-analysis, the overall risk of relapse after anti-TNF withdrawal was 30%-40% at 1 year, and 50% at 2 years, but there is a lack of controlled, high-quality studies in this area. 30 The aims of the present study were to systematically review and meta-analyse the efficacy and safety of discontinuation of IMs or biologics in both UC and CD.…”

Section: Introductionmentioning

confidence: 99%

Systematic review with meta‐analysis: the effects of immunomodulator or biological withdrawal from mono‐ or combination therapy in inflammatory bowel disease

Dohos

Hanák

Szakács

et al. 2020

Aliment Pharmacol Ther

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SummaryBackgroundWithdrawal of treatment is a common therapeutic problem in patients with long‐standing remission of inflammatory bowel disease.AimsTo evaluate the relapse rate in patients with quiescent inflammatory bowel disease after cessation of biologic or immunomodulator therapy.MethodsWe searched five databases for studies evaluating disease relapse after withdrawal of monotherapy or a drug from combination therapy in Crohn's disease or ulcerative colitis. In meta‐analysis, risk ratios (RR) were calculated with 95% confidence intervals (CI).ResultsTen randomised controlled trials (587 patients) were included in the meta‐analysis, and another nine studies in systematic review. Withdrawal of immunomodulator monotherapy resulted in a significantly higher risk of relapse within 24 months of follow‐up compared to ongoing therapy in Crohn's disease, but not in ulcerative colitis (RR = 2.06, CI: 1.53‐2.77 and RR = 1.39, CI: 0.85‐2.26, respectively). Trial sequential analysis indicated that further studies with similar design are unlikely to change the significant association on relapse rates after withdrawing immunomodulator monotherapy in patients with Crohn's disease. Discontinuation of an immunomodulator from combination with biologics did not show a higher risk of relapse than continuation of both drugs (RR = 1.30, CI: 0.81‐2.08). The relapse rate increased after withdrawal of biologic monotherapy, whereas contradictory results were observed after biologic withdrawal from combination regimens.ConclusionContinuing immunomodulator monotherapy should remain the preferred approach among patients with Crohn's disease, although long‐term toxicity is a concern. Further randomised controlled trials are warranted in ulcerative colitis and on combination regimens including biologics.

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The shining DIAMOND for evidence-based treatment strategies for Crohn’s disease

et al. 2020

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Withdrawal of thiopurines in Crohn’s disease treated with scheduled adalimumab maintenance: a prospective randomised clinical trial (DIAMOND2)

Cited by 23 publications

References 26 publications

De-escalation of immunomodulator and biological therapy in inflammatory bowel disease

De-escalation of immunomodulator and biological therapy in inflammatory bowel disease

Systematic review with meta‐analysis: the effects of immunomodulator or biological withdrawal from mono‐ or combination therapy in inflammatory bowel disease

The shining DIAMOND for evidence-based treatment strategies for Crohn’s disease

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