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

Nakase, Hiroshi; Matsumoto, Takayuki; Watanabe, Kenji; Hisamatsu, Tadakazu

doi:10.1007/s00535-020-01702-x

Cited by 2 publications

(4 citation statements)

References 54 publications

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“…Nevertheless, the previous studies confirmed the efficacy of low-dose thiopurines in Japanese UC patients [ 22 , 26 ]. One possible explanation for this finding is the low activity of thiopurine S-methyltransferase in Japanese patients [ 27 ] and high prevalence of NUDT15 polymorphisms. In fact, Komiyama et al [ 28 ] found that the mean 6-TGN concentration was within the therapeutic range (342.3 pmol/8 × 10 8 red blood cells) under low-dose thiopurine treatment (mean dose, 29.8 mg/day as 6-MP) among 134 Japanese IBD patients.…”

Section: Discussionmentioning

confidence: 99%

White Blood Cell Counts and Future Relapse in Ulcerative Colitis under Low-Dose Thiopurine Treatment in Real-World Practice: A 3-Year Japanese Multi-Center Retrospective Cohort Study

Kiyohara,

Yamazaki,

Moriya

et al. 2023

Inflamm Intest Dis

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Introduction Whether white blood cell (WBC) counts are predictors for the effectiveness of thiopurine treatment in ulcerative colitis (UC) has been inconclusive in previous studies with small sample sizes. We investigated the association between WBC counts and future relapses in UC patients in a large-scale multi-center study. Methods This retrospective cohort study enrolled a total of 723 UC patients in remission from 33 hospitals and followed up for three years. Relapse was defined as a need for treatment intensification. The risk of relapse was compared among patients with the baseline WBC counts<3000/µL (N=31), 3000–4000/µL (N=167), 4000–5000/µL (N=241), and ≥5000/µL (N=284) using a Cox regression model analysis. Moreover, exploratory analyses were conducted to identify other factors predicting relapse. Results During a median follow-up period of 1095 (interquartile range, 1032–1119) days, relapse occurred in 17.2% (125/723). In a crude analysis, WBC counts were not associated with relapse; hazard ratios (HRs) [95% confidence interval (CI)] were 1.50 [0.74–3.06], 1.02 [0.66–1.59] and 0.67 [0.43–1.05] in WBC<3000/µL, 3000–4000/µL, and 4000–5000/µL groups, respectively (WBC≥5000/µL group, as reference). Multivariable-adjusted analyses showed similar results; HRs [95% CI] were 1.21 [0.59–2.49], 1.08 [0.69–1.69], and 0.69 [0.44–1.07], in <3000/µL, 3000–4000/µL, and 4000–5000/µL group, respectively. In the exploratory analyses, thiopurine use <1 year and a mean corpuscular volume <90 fL were predictors for relapse. Discussion/Conclusion WBC counts were not predictors for future relapses in patients with UC treated with thiopurine as a maintenance therapy.

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Section: Discussionmentioning

confidence: 99%

White Blood Cell Counts and Future Relapse in Ulcerative Colitis under Low-Dose Thiopurine Treatment in Real-World Practice: A 3-Year Japanese Multi-Center Retrospective Cohort Study

Kiyohara,

Yamazaki,

Moriya

et al. 2023

Inflamm Intest Dis

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“…The presence of low drug levels and absent or low antibody titers may be an indication to increase the dose of the biological or shorten the dosing interval [ 113 ]. Indeed, an analysis of the DIAMOND study comparing adalimumab with adalimumab plus azathioprine in immunosuppressant-naive CD patients found a significant difference in trough levels of adalimumab in patients with and without clinical remission [ 123 ]. Further analysis suggested the significance of therapeutic drug monitoring including both trough levels and 6-thioguanune nucleotide levels when managing CD patients receiving combination therapy and independent associations between female sex, increased body and low adalimumab trough levels.…”

Section: Consensus Recommendationsmentioning

confidence: 99%

“…However, as with anti-TNFα therapy, the rate of relapse following immunomodulator cessation increases with longer periods of follow-up [ 244 ]. This has led to the suggestion that, in patients who receive combination therapy for more than 6 months, triple remission consisting of corticosteroid-free clinical remission, endoscopic remission, and serological remission allows consideration of thiopurine withdrawal [ 123 ]. Finally, the impact of immunomodulator discontinuation can be reduced by either partial withdrawal in terms of dose reduction rather than complete cessation or selective withdrawal in patients who have received concomitant treatment for longer periods.…”

Section: Consensus Recommendationsmentioning

confidence: 99%

“…Finally, the impact of immunomodulator discontinuation can be reduced by either partial withdrawal in terms of dose reduction rather than complete cessation or selective withdrawal in patients who have received concomitant treatment for longer periods. In any case, evidence from studies such as DIAMOND2 suggest that an individualized strategy of withdrawal should be implemented [ 123 ]. This should include ongoing assessment of measures of efficacy, including endoscopic or cross-sectional imaging parameters, biomarkers, and therapeutic drug monitoring.…”

Section: Consensus Recommendationsmentioning

confidence: 99%

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Treatment escalation and de-escalation decisions in Crohn’s disease: Delphi consensus recommendations from Japan, 2021

et al. 2023

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Background We aimed to develop criteria for treatment intensification in patients with (1) luminal Crohn’s disease (CD), (2) CD with perianal disease and/or fistula, (3) CD with small bowel stenosis, (4) in the postoperative setting, and (5) for discontinuing or reducing the dose of treatment in patients with CD. Methods PubMed and Embase were searched for studies published since 1998 which may be relevant to the five defined topics. Results were assessed for relevant studies, with preference given to data from randomized, controlled studies. For each question, a core panel of 12 gastroenterologists defined the treatment target and developed statements, based on the literature, current guidelines, and relevant additional studies. The evidence supporting each statement was graded using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). A modified Delphi process was used to refine statements and gain agreement from 54 Japanese specialists at in-person and online meetings conducted between October 2020 and April 2021. Results Seventeen statements were developed for treatment intensification in luminal CD (targeting endoscopic remission), six statements for treatment intensification in perianal/fistulizing CD (targeting healing of perianal lesions and complete closure of the fistula), six statements for treatment intensification in CD with small bowel stenosis (targeting resolution of obstructive symptoms), seven statements for treatment intensification after surgery (targeting endoscopic remission), and five statements for discontinuing or reducing the dose of treatment in patients with CD. Conclusions These statements provide guidance on how and when to intensify or de-intensify treatment for a broad spectrum of patients with CD.

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

Cited by 2 publications

References 54 publications

White Blood Cell Counts and Future Relapse in Ulcerative Colitis under Low-Dose Thiopurine Treatment in Real-World Practice: A 3-Year Japanese Multi-Center Retrospective Cohort Study

White Blood Cell Counts and Future Relapse in Ulcerative Colitis under Low-Dose Thiopurine Treatment in Real-World Practice: A 3-Year Japanese Multi-Center Retrospective Cohort Study

Treatment escalation and de-escalation decisions in Crohn’s disease: Delphi consensus recommendations from Japan, 2021

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