Thiopurine Monotherapy Is Effective in Maintenance of Mild-Moderate Inflammatory Bowel Disease

Barber, Grant E.; Hendler, Steven; Choe, Monica; Keyashian, Kian; Lechner, Sarah; Limketkai, Berkeley N.; Limsui, David

doi:10.1007/s10620-021-06947-x

Cited by 3 publications

(4 citation statements)

References 35 publications

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“…[steroid-free] clinical remission, drug persistence and prevention of disease progression). [16][17][18][19][20][21][22]42,43 However, most of these studies were limited as a result of modest sample sizes, duration of follow-up or both. Effectiveness defined as clinical remission, regardless of corticosteroid use, escalation to biological or surgery, was reported in a Dutch cohort study of 363 patients with observed effectiveness rates of 63%, 51% and 42% at 1, 2 and 5 years, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…In a number of observational cohort studies, it has been reported that therapeutic benefit may be observed in 40%–75% of patients using thiopurine monotherapy in CD or UC with various definitions for effectiveness (e.g. [steroid‐free] clinical remission, drug persistence and prevention of disease progression) 16–22,42,43 . However, most of these studies were limited as a result of modest sample sizes, duration of follow‐up or both.…”

Section: Discussionmentioning

confidence: 99%

“…In observational studies in real‐world settings it has been suggested that thiopurine monotherapy benefits IBD patients. However, these studies were limited by relatively small numbers or short follow‐up of patients 16–23 . Furthermore, in a recent large observational study from the UK, a lower, overall effectiveness rate of thiopurine monotherapy in CD patients as compared to UC patients was reported and the authors suggested a potential re‐evaluation of thiopurine use in CD 24 …”

Section: Introductionmentioning

confidence: 99%

“…However, these studies were limited by relatively small numbers or short follow-up of patients. [16][17][18][19][20][21][22][23] Furthermore, in a recent large observational study from the UK, a lower, overall effectiveness rate of thiopurine monotherapy in CD patients as compared to UC patients was reported and the authors suggested a potential re-evaluation of thiopurine use in CD. 24 Another frequently debated concern over thiopurines is its safety profile, including an increased risk of (viral) infections (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Classic drugs in the time of new drugs: real‐world, long‐term outcomes of thiopurine monotherapy in 1016 patients with inflammatory bowel disease

Ardabili

Mujagic

Oostenbrug

et al. 2022

Aliment Pharmacol Ther

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Summary Background Thiopurines remain recommended as maintenance therapy in patients with inflammatory bowel disease (IBD). Despite their widespread use, long‐term effectiveness data are sparse and safety is an increasingly debated topic which thwarts proper delineation in the current IBD treatment algorithm. Aims To document effectiveness and safety of thiopurine monotherapy in patients with IBD, using the population‐based IBD South‐Limburg (IBDSL) cohort Methods All patients starting thiopurine monotherapy as maintenance between 1991 and 2014 were included. Therapy was defined as effective if there was no escalation to biologicals, no course of corticosteroids, no surgery and no hospitalisation for active disease during treatment. Long‐term effectiveness was assessed by adjusting for differences in follow‐up using Kaplan–Meier analyses. Mid‐ to long‐term safety regarding cancer incidence and clinically relevant liver disease was documented. Results In total, 1016 patients (643 Crohn's disease [CD]; 373 ulcerative colitis [UC]) received thiopurine monotherapy at a median of 15.2 (Q1‐Q3 4.2–48.5) months after diagnosis. During follow‐up, effectiveness rates at 1, 5 and 10 years were 64%, 45%, 32%, respectively, in CD and and 66%, 41%, 36%, respectively in UC. No statistically significant differences in effectiveness were observed after stratification for era of initiation (pre‐biological vs biological, CD: p = 0.56; UC: p = 0.43). Sixteen non‐melanoma skin cancers (incidence rate [IR] 3.33/1000 PY), five lymphomas (IR 1.04/1000 PY) and one urinary tract cancer (IR 0.21/1000 PY) were recorded. Two cases of portal hypertension were identified. Conclusion In real‐world practice, thiopurine monotherapy remains effective, safe and durable for patients with CD or UC, including in the era of biologics.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Classic drugs in the time of new drugs: real‐world, long‐term outcomes of thiopurine monotherapy in 1016 patients with inflammatory bowel disease

Ardabili

Mujagic

Oostenbrug

et al. 2022

Aliment Pharmacol Ther

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Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis

Ranjan

Kumar

Vuyyuru

et al. 2023

Journal of Crohn's and Colitis

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Background and Aims Thiopurines are viable option for the treatment of inflammatory bowel disease (IBD) in resource limited countries. However, data on the effect of disease duration at thiopurines initiation on long-term effectiveness is limited. Method We performed a propensity matched analysis of a retrospective cohort of patients with ulcerative colitis (UC) and Crohn’s disease (CD). Patients initiated on thiopurines early in the disease course (≤2 years) were compared to those started late (>2 years). Effectiveness defined as no requirement for hospitalization, anti-TNF agents, surgery, and minimum steroid requirement (≤ 1 steroid course in 2years) during follow-up. Results Nine-hundred eighty-eight (UC:720, CD:268) patients were included [(male: 665 (60.8%), median age: 40(32-51) years, median follow up: 40 (19-81) months]. Overall effectiveness at 5 and 10 years was 79% and 72% in UC, and 69% and 63% in CD respectively. After propensity score matching, there was no difference in 5- and 10-year effectiveness between early and late thiopurine initiation groups either for UC (81% and 80% vs. 82% and 74%; p=0.92) or CD (76% and 66% vs. 72% and 51%, p=0.32). Male sex for UC (negative: HR:0.67, 95% CI:0.45-0.97; p=0.03), and ileal involvement (positive: HR: 3.03, 95% CI:1.32-6.71; p= 0.008), steroid dependent disease (positive: HR: 2.70, 95% CI:1.26-5.68; p= 0.01) and adverse events (negative: HR: 0.47, 95%CI:0.27-0.80; p=0.005) for CD were predictors of thiopurine effectiveness. Conclusion Thiopurines have sustained long-term effectiveness in both UC and CD. However, early thiopurine initiation had no better effect on long-term disease outcome compared to late initiation.

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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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Thiopurine Monotherapy Is Effective in Maintenance of Mild-Moderate Inflammatory Bowel Disease

Cited by 3 publications

References 35 publications

Classic drugs in the time of new drugs: real‐world, long‐term outcomes of thiopurine monotherapy in 1016 patients with inflammatory bowel disease

Classic drugs in the time of new drugs: real‐world, long‐term outcomes of thiopurine monotherapy in 1016 patients with inflammatory bowel disease

Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis

Precision medicine and drug optimization in adult inflammatory bowel disease patients

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