Thiopurine Treatment in Ulcerative Colitis: A Critical Review of the Evidence for Current Clinical Practice

Abstract Background Due to toxicity problems and controversial evidence, thiopurine use in ulcerative colitis (UC) has faced a lot of criticism. We present a critical review of the literature on efficacy of thiopurines in UC. Methods Studies evaluating therapeutic efficacy of thiopurine remission induction and/or maintenance treatment in UC were identified using the Cochrane Library, MEDLINE, and EMBASE. Results Out of 5 randomized trials on thiopurine induction treatment, 3 demonstrated a significant effect of thiopurine treatment vs mesalamine or placebo in steroid-dependent UC patients: (1) lower endoscopic activity scores, (2) higher clinical remission rates, and (3) more patients who discontinued steroids. Two found no significant difference in clinical and endoscopic remission of azathioprine compared with sulfasalazine or placebo in patients with active UC. Out of 7 randomized trials on thiopurine maintenance treatment, 4 demonstrated significant higher clinical and endoscopic remission rates in thiopurine-treated patients compared with placebo or mesalamine. Three found no significant difference in clinical and endoscopic remission of thiopurine maintenance treatment compared with sulfasalazine or placebo. Conclusions All studies that investigated thiopurine treatment in UC had shortcomings, such as lack of sufficient power, no use of blinding, allowed concomitant treatment with steroids, and no endoscopy to confirm active disease at study entry or to evaluate therapeutic efficacy. Hence, current clinical practice of thiopurine treatment in UC is based on minimal and controversial evidence. This underscores the need for clinical studies with sufficient power and objective end points in order to determine efficacy of thiopurines in UC. 10.1093/ibd/izx025_video1 izx025.video1 5732762967001

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A Comparison of Short- and Long-Term Therapeutic Outcomes of Infliximab- versus Tacrolimus-Based Strategies for Steroid-Refractory Ulcerative Colitis

Gastroenterology Research and Practice ◽

10.1155/2016/3162595 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 17

Author(s):

Katsuya Endo ◽

Motoyuki Onodera ◽

Hisashi Shiga ◽

Masatake Kuroha ◽

Tomoya Kimura ◽

...

Keyword(s):

Ulcerative Colitis ◽

Therapeutic Efficacy ◽

Maintenance Treatment ◽

Remission Rate ◽

Rank Test ◽

Clinical Response Rate ◽

Therapeutic Outcomes ◽

Significant Difference ◽

Steroid Refractory

Background/Aims. Antitumor necrosis factor antibodies and calcineurin inhibitors have shown good therapeutic efficacy for steroid-refractory ulcerative colitis (UC). Although some studies have compared the efficacy of infliximab (IFX) and cyclosporin A, there are no published studies comparing IFX and tacrolimus (Tac). This study aimed to compare therapeutic efficacies between IFX- and Tac-based strategies for steroid-refractory UC.Methods. Between July 2009 and August 2013, 95 patients with steroid-refractory UC received either IFX(n=48)or Tac(n=47)in our hospital. In the IFX group, the patients continued to receive maintenance treatment with IFX. In the Tac group, patients discontinued Tac treatment up to 3 months and subsequently received thiopurine. We retrospectively compared the therapeutic outcomes between the groups.Results. There was no significant difference in the colectomy-free rate, clinical remission rate, and clinical response rate at 2 months between the groups. However, relapse-free survival was significantly higher in the IFX group than in the Tac group (p<0.001; log-rank test). The proportions of serious adverse events did not differ between the groups.Conclusion.The findings of our study showed that IFX and Tac have similar short-term therapeutic efficacy for steroid-refractory UC. Maintenance treatment with IFX, however, yields better long-term outcomes than Tac-thiopurine bridging treatment.

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Pulse Lavage Fails to Significantly Reduce Bone Marrow Content in Osteochondral Allografts: A Histological and DNA Quantification Study

The American Journal of Sports Medicine ◽

10.1177/0363546519864716 ◽

2019 ◽

Vol 47 (11) ◽

pp. 2723-2728 ◽

Cited By ~ 2

Author(s):

Luiz Felipe Ambra ◽

Laura de Girolamo ◽

Andreas H. Gomoll

Keyword(s):

Bone Marrow ◽

Clinical Practice ◽

Subchondral Bone ◽

Dna Content ◽

Size Group ◽

Current Clinical Practice ◽

Allogenic Bone ◽

Allogenic Bone Marrow ◽

Significant Difference ◽

Pulse Lavage

Background: Current clinical practice calls for pulse lavage of fresh osteochondral allografts (OCAs) to reduce immunogenicity; however, there is limited evidence of its effectiveness in reducing allogenic bone marrow elements. Purpose: To evaluate the effectiveness of pulse lavage in removing marrow elements from trabecular bone in fresh OCA transplantation. Study Design: Controlled laboratory study. Methods: The authors evaluated 48 fresh OCA plugs with 4 different common sizes (14- and 24-mm diameter, 6- and 10-mm thickness). Within each size group, half of the samples underwent pulse lavage (n = 6) with saline solution and half were left untreated (no lavage; control group, n = 6). For each treatment and size group, 3 samples were analyzed for DNA content as an indicator of the number of residual nucleated cells; the other 3 samples were histologically analyzed to assess the presence and distribution of cells within subchondral bone pores in 3 specific locations within the plug: peripheral, intermediate, and core. Results: Osteochondral plugs treated with pulse lavage did not show a significant decrease in DNA content in comparison with untreated plugs. Overall, histological analysis did not show a significant difference between the treated and untreated groups ( P = .23). Subgroup analysis by size demonstrated decreased marrow content in treated versus untreated groups in the thinner plug sizes (14 × 6 mm and 24 × 6 mm). Histological evaluation by zone demonstrated a significant difference between groups only in the peripheral zone ( P = .04). Conclusion: Pulse lavage has limited effectiveness in removing marrow elements, in particular in plugs that are larger in diameter and, more importantly, in thickness. Better techniques for subchondral bone treatment are required for more thorough removal of potentially immunogenic marrow elements. Clinical Relevance: OCA transplantation has become an established treatment modality. Unfortunately, OCA is not without limitations, chiefly its mode of failure through inadequate integration of the allograft subchondral bone with subsequent collapse. In an effort to improve integration, current clinical practice calls for pulse lavage to remove allogenic bone marrow from the subchondral bone in hopes of decreasing the immunogenicity of the graft and facilitating revascularization.

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Frequency of equivocation in surgical meta-evidence: a review of systematic reviews within IBD literature

BMJ Open ◽

10.1136/bmjopen-2017-018715 ◽

2017 ◽

Vol 7 (12) ◽

pp. e018715 ◽

Cited By ~ 3

Author(s):

John D Delaney ◽

John T Holbrook ◽

Robert K Dewar ◽

Patrick J Laws ◽

Alexander F Engel

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Clinical Practice ◽

Systematic Reviews ◽

Bowel Disease ◽

Predisposing Factors ◽

Significant Difference ◽

Inflammatory Bowel ◽

Level 1

ObjectiveTo assess the level of equivocation among level 1 evidence in ulcerative colitis and Crohn’s disease and determine whether any predisposing factors are present.MethodMEDLINE, Embase, CINHAL and Cochrane were searched from 2006 to 2017. Papers were scored using AMSTAR and categorised into surgical (S), medical (M) or medical and surgical (MS) groups. The ability of each paper to make a recommendation and conclusiveness in doing so was recorded.Results278 papers were assessed. 82% (n=227) could make a recommendation, 18% (n=51) could not. There was a significant difference in ability to provide a recommendation between S and M (P=0.003) but not MS and M (P=0.022) nor S and MS (P=0.79). Where a recommendation was made, S papers were more likely to be tempered than M papers (P=0.014) but not MS papers (P=0.987).ConclusionsSurgical meta-evidence within the inflammatory bowel disease domain is more than twice as likely as medical meta-evidence to be unable to provide a recommendation for clinical practice. Where a recommendation was made, surgical reviews were twice as likely to temper their conclusion.

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Tu1131 The Effect of Ulcerative Colitis Remission Status on the Ability to Maintain or Achieve Clinical and Endoscopic Remission After 12-Month Maintenance Treatment With MMx®* Mesalamine

Gastroenterology ◽

10.1016/s0016-5085(13)62847-4 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-770

Author(s):

David T. Rubin ◽

Susi Inglis ◽

Elizabeth Magee ◽

Paul Streck ◽

Dory M. Solomon ◽

...

Keyword(s):

Ulcerative Colitis ◽

Maintenance Treatment ◽

Remission Status ◽

Endoscopic Remission

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Critical review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology

Supportive Care in Cancer ◽

10.1007/s00520-016-3412-y ◽

2016 ◽

Vol 25 (1) ◽

pp. 221-228 ◽

Cited By ~ 12

Author(s):

Jessica E Morgan ◽

Hadeel Hassan ◽

Julia V Cockle ◽

Christopher Lethaby ◽

Beki James ◽

...

Keyword(s):

Clinical Practice ◽

Antifungal Therapy ◽

Clinical Practice Guidelines ◽

Practice Guidelines ◽

Critical Review ◽

Current Clinical Practice ◽

Paediatric Haematology

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OP24 Efficacy and safety of upadacitinib induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from the phase 3 U-ACHIEVE study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab075.023 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S022-S024

Author(s):

S Danese ◽

S Vermeire ◽

W Zhou ◽

A Pangan ◽

J Siffledeen ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Induction Therapy ◽

Clinical Remission ◽

Janus Kinase ◽

Phase 3 ◽

Mayo Score ◽

Significant Difference ◽

Endoscopic Remission ◽

Secondary Endpoints

Abstract Background An unmet therapeutic need remains in patients with ulcerative colitis (UC). U-ACHIEVE is one of two phase 3 induction trials evaluating the safety and efficacy of the selective Janus kinase–1 inhibitor upadacitinib (UPA) 45 mg once daily (QD) in adults with UC. Methods U-ACHIEVE is a multicentre, double-blind, placebo (PBO)–controlled trial (NCT02819635) that randomized patients with moderately to severely active UC 2:1 to UPA 45 mg QD or PBO for 8 weeks. Patients were stratified by response to biologic therapy (inadequate vs non–inadequate responder), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or >7). The primary endpoint was proportion of patients achieving clinical remission (per adapted Mayo Score) at week 8.Ranked secondary endpoints included endoscopic improvement, endoscopic remission, and clinical response per adapted Mayo Score at week 8; clinical response per partial adapted Mayo Score at week 2; and histologic-endoscopic mucosal improvement at week 8. Non-responder imputation incorporating multiple imputations for missing data due to COVID-19 are reported. Safety was assessed through week 8. Results 474 patients were randomized (UPA, n=319; PBO, n=155). Baseline characteristics were well balanced between groups (Table 1). A significantly higher proportion of patients receiving UPA (26.1%) vs PBO (4.8%) achieved clinical remission at week 8 (adjusted treatment difference [95% CI], 21.6% [15.8, 27.4]; P<0.001; Figure 1). For all ranked secondary endpoints, UPA was superior to PBO (P<0.001; Figure 1). A significant difference in clinical response favouring UPA vs PBO was seen as early as week 2 (60.1% vs 27.3%) and was sustained over 8 weeks (79.0% vs 41.6%; Figure 2). There were more serious adverse events (AEs), severe AEs, and AEs leading to study drug discontinuation with PBO (Table 2). The most common AEs were acne, creatine phosphokinase elevation, and nasopharyngitis with UPA and worsening of UC and anaemia with PBO. Incidence of serious infection was similar between UPA and PBO. Neutropenia and lymphopenia were reported more frequently with UPA vs PBO (Table 2).No adjudicated gastrointestinal perforation, major cardiovascular AEs, or thrombotic events and no active tuberculosis, malignancy, or deaths were reported. Conclusion In patients with moderately to severely active UC, UPA 45 mg QD induction therapy was superior to PBO in inducing clinical remission/response, and endoscopic remission/response over 8 weeks; responses were significant and rapid. UPA 45 mg QD was well tolerated; safety was comparable with the known safety profile of UPA, and no new safety signals were identified.

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Adjuvant Chemotherapy in Resected Lung Cancer: Two-Year Experience in a University Hospital

Canadian Respiratory Journal ◽

10.1155/2008/462147 ◽

2008 ◽

Vol 15 (5) ◽

pp. 270-274 ◽

Cited By ~ 7

Author(s):

Nicole Bouchard ◽

Francis Laberge ◽

Bruno Raby ◽

Sylvie Martin ◽

Yves Lacasse

Keyword(s):

Lung Cancer ◽

Clinical Practice ◽

Adjuvant Chemotherapy ◽

Surgical Resection ◽

Randomized Trials ◽

Medical Oncology ◽

Early Stage ◽

University Hospital ◽

Quebec City ◽

Significant Difference

BACKGROUND: Randomized trials have confirmed the benefits of adjuvant chemotherapy in improving survival in resected early-stage non-small-cell lung cancer (NSCLC). The extent to which these results have translated into clinical practice is unknown.OBJECTIVE: To examine the referral pattern of patients with resected lung cancer to adjuvant chemotherapy, and to compare compliance and toxicities with current literature.METHODS: A retrospective analysis of all patients who underwent a surgical resection for lung cancer at Laval Hospital (Quebec City, Quebec) from March 2004 to January 2006 was conducted.RESULTS: A total of 258 patients underwent surgery. Seven patients were excluded because of early postoperative death, and two patients were excluded because of incomplete data. Data from 249 patients were analyzed (94% NSCLC). Fifty per cent were referred to medical oncology for consideration of adjuvant chemotherapy, including 37 of 61 patients with stage II NSCLC. One hundred patients received chemotherapy. No significant difference in age, sex, comorbidities and surgical procedures was observed between those who received chemotherapy and those who did not. Chemotherapy was initiated 47 days (median) after the surgery and consisted mainly of cisplatin-vinorelbine (38%), cisplatin-etoposide (22%) and carboplatin-paclitaxel (20%). Sixty-six per cent of the patients completed all four cycles. Grade 3 or 4 toxicities consisted mainly of fatigue (23%) and cytopenia (40%). No death was registered; 15% had to be hospitalized because of adverse effects.CONCLUSION: Although adjuvant chemotherapy is gaining acceptance in clinical practice, more patients should be referred to medical oncology following surgical resection. Compliance and toxicity are similar to or better than those described in published randomized trials.

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