Dataset Information

Association Between Use of Thiopurines or Tumor Necrosis Factor Antagonists Alone or in Combination and Risk of Lymphoma in Patients With Inflammatory Bowel Disease.

ABSTRACT: An increased risk of lymphoma has been reported among patients receiving thiopurines for inflammatory bowel disease (IBD). The risk of lymphoma associated with anti-tumor necrosis factor (TNF) agents either alone or in combination with thiopurines is uncertain.To assess the risk of lymphoma associated with thiopurines and anti-TNF agents, used alone or in combination, for the management of IBD.Nationwide cohort study based on French National Health Insurance databases. Patients aged 18 years or older identified with IBD were included from January 1, 2009, through December 31, 2013, and followed up until December 31, 2015.At each time of the follow-up, patients were categorized as being exposed to thiopurine monotherapy, anti-TNF monotherapy, or combination therapy, or being unexposed.The primary outcome was incident lymphoma.Among the 189?289 patients included (54% women; median age, 43 years [interquartile range, 32-56 years]) and followed up for a median of 6.7 years, 123?069 were never exposed during follow-up, 50?405 were exposed to thiopurine monotherapy, 30?294 to anti-TNF monotherapy, and 14?229 to combination therapy. Overall, 336 lymphoma cases occurred: 220 in unexposed patients (incidence rate [IR] per 1000 person-years, 0.26; 95% CI, 0.23-0.29), 70 in patients exposed to thiopurine monotherapy (IR, 0.54; 95% CI, 0.41-0.67), 32 in patients exposed to anti-TNF monotherapy (IR, 0.41; 95% CI, 0.27-0.55), and 14 in patients exposed to combination therapy (IR, 0.95; 95% CI, 0.45-1.45). In a multivariable Cox model, compared with unexposed patients, the risk of lymphoma was higher among those exposed to thiopurine monotherapy (adjusted hazard ratio [aHR], 2.60; 95% CI, 1.96-3.44; P?

SUBMITTER: Lemaitre M

PROVIDER: S-EPMC5818785 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association Between Use of Thiopurines or Tumor Necrosis Factor Antagonists Alone or in Combination and Risk of Lymphoma in Patients With Inflammatory Bowel Disease.

Lemaitre Magali M Kirchgesner Julien J Rudnichi Annie A Carrat Fabrice F Zureik Mahmoud M Carbonnel Franck F Dray-Spira Rosemary R

JAMA 20171101 17

<h4>Importance</h4>An increased risk of lymphoma has been reported among patients receiving thiopurines for inflammatory bowel disease (IBD). The risk of lymphoma associated with anti-tumor necrosis factor (TNF) agents either alone or in combination with thiopurines is uncertain.<h4>Objective</h4>To assess the risk of lymphoma associated with thiopurines and anti-TNF agents, used alone or in combination, for the management of IBD.<h4>Design, setting, and participants</h4>Nationwide cohort study ...[more]

PMID: 29114832

Similar Datasets

Project description:Introduction: Tumor necrosis factor antagonists (anti-TNF) therapies are used for the management of moderate to severe inflammatory bowel disease (IBD). Anti-TNF combination therapy, with immunomodulators, has been shown to reduce immunogenicity, especially for infliximab, improve treatment success rate and patient outcomes. We evaluated factors associated with gastroenterologists adherence to anti-TNF combination therapy. Methods: A retrospective cohort study was performed to evaluate the adherence of gastroenterologists (n = 14), at an inflammatory bowel disease center, to anti-TNF combination therapy. Records of patients who received Infliximab (n = 137) or adalimumab (n = 152) were obtained and their ordering physicians' data was analyzed. Gastroenterologists were divided into six groups according to their age and interest in IBD. The baseline characteristics of their patients were also obtained. Results: The proportion of patients on combination therapy in the young gastroenterologists group was higher than those in the senior gastroenterologists group for both infliximab (83.2 vs. 55.6%, respectively, P < 0.001) and adalimumab (59 vs. 30.8%, respectively, P < 0.001). Gastroenterologists with interest in inflammatory bowel disease (IBD interest group) had also more proportion of patients on adalimumab combination therapy compared to gastroenterologists with no interest in IBD (non-IBD interest group) (61.7 vs. 35.2%, respectively, P < 0.001). Gastroenterologists who were both young and have interest in IBD had more proportion of patients on combination therapy than those who were senior or had no interest in IBD for both infliximab (89.4 vs. 63.4%, respectively, P < 0.001) and adalimumab (75.9 vs. 33%, P < 0.001). The IBD interest group was also requesting more antidrug antibody level tests than those in the non-IBD interest group (41.4 vs. 12.3 tests, respectively, P < 0.001). Conclusion: Young gastroenterologists are more likely to prescribe anti-TNF infliximab and adalimumab combination therapy than senior gastroenterologists. In addition, gastroenterologists with IBD interest are more likely to prescribe adalimumab combination therapy than gastroenterologists with no IBD interest. Moreover, young gastroenterologists who have interest in IBD are more likely to prescribe both infliximab and adalimumab combination therapy than senior gastroenterologists or those with no IBD interest. In addition, gastroenterologists with IBD interest requested more anti-TNF serum drug concentrations and antidrug antibody level tests than those with no IBD interest.

Project description:Thiopurines have been a cornerstone in the treatment of inflammatory bowel disease (IBD). Although they have been used for more than 50 years, there are still some unsolved issues about their efficacy and, also, some safety concerns, mainly the risk of myelosuppression and life-threatening lymphoproliferative disorders. Furthermore, the development of biological therapy raises the question whether there is still a role for thiopurines in the IBD treatment algorithm. On the other hand, limited cost and wide availability make thiopurines a reasonable option in settings of limited resources and increasing prevalence of IBD. In fact, there is a growing interest in optimizing thiopurine therapy, since pharmacogenomic findings suggest that a personalized approach based on the genotyping of some molecules involved in its metabolism could be useful to prevent side effects. Polymorphisms of thiopurine methyltransferase enzyme (TPMT) that result in low enzymatic activity have been associated with an increased risk of myelotoxicity, especially in Caucasians; however, in Asians it is assumed that the variants of nudix hydrolase 15 (NUDT15) are more relevant in the development of toxicity. Age is also important, since in elderly patients the risk of complications seems to be increased. Moreover, the primo-infection of Epstein Barr virus and cytomegalovirus under thiopurine treatment has been associated with severe lymphoproliferative disorders. In addition to assessing individual characteristics that may influence thiopurines treatment outcomes, this review also discusses other strategies to optimize the therapy. Low-dose thiopurines combined with allopurinol can be used in hypermethylators and in thiopurine-related hepatotoxicity. The measurement of metabolites could be useful to assess compliance, identify patients at risk of adverse events and also facilitating the management of refractory patients. Thioguanine is also a rescue therapy in patients with toxicity related to conventional thiopurine therapy. Finally, the current indications for thiopurines in monotherapy or in combination with biologics, as well as the optimal duration of treatment, are also reviewed.

Project description:ImportanceObservational comparative effectiveness studies can inform the positioning of biologic therapies for older patients with inflammatory bowel disease (IBD) who are underrepresented in clinical trials.ObjectiveTo compare the effectiveness and safety of vedolizumab vs tumor necrosis factor (TNF) for older patients with IBD.Design, setting, and participantsThis active comparator, new-user design, comparative effectiveness study was conducted between January 1, 2005, and December 31, 2018, among 754 older patients (aged ≥50 years) with IBD from the Danish National Patient Register. The mean follow-up after treatment initiation took place at 32 to 40 weeks. Statistical analysis was performed from February 1 to April 27, 2022.InterventionsTreatment with vedolizumab or TNF antagonists.Main outcomes and measuresThe primary effectiveness outcome was treatment failure, defined as the composite risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after initiation of treatment with biologic therapy. Secondary effectiveness outcomes were time to each individual component of the composite effectiveness outcome. The primary safety outcome was the risk of serious infections, defined as infections requiring hospitalization. A 1:1 propensity score-matched analysis was conducted, accounting for patient-, disease-, and treatment-associated factors.ResultsThe study compared 377 older patients with IBD with incident use of vedolizumab (202 women [53.6%]; mean [SD] age, 61.2 [8.3] years; 177 [46.9%] with Crohn disease) vs 377 patients with incident use of TNF antagonists (206 women [54.6%]; mean [SD] age, 61.3 [8.1] years; 182 [48.3%] with Crohn disease). Overall, vedolizumab was associated with an increased risk of treatment failure compared with TNF antagonists (1-year risk, 45.4% vs 34.7%; adjusted hazard ratio [HR], 1.31; 95% CI, 1.02-1.69), including higher risk of IBD-related hospitalization (1-year risk, 27.8% vs 16.3%; adjusted HR, 1.48; 95% CI, 1.03-2.15) and IBD-related major abdominal surgery (1-year risk, 21.3% vs 8.0%; adjusted HR, 2.39; 95% CI, 1.45-3.94). In subgroup analysis by IBD phenotype, among patients with Crohn disease, vedolizumab was associated with a 77% higher risk of treatment failure (adjusted HR, 1.77; 95% CI, 1.21-2.58), while no difference in risk of treatment failure was seen among patients with ulcerative colitis (adjusted HR, 1.04; 95% CI, 0.75-1.43; P = .03 for interaction). There was no significant difference in the risk of serious infections, overall (1-year risk, 8.2% vs 8.7%; adjusted HR, 1.04; 95% CI, 0.58-1.85) and by IBD phenotype.Conclusions and relevanceIn this comparative effectiveness study of older patients with IBD, vedolizumab was associated with a higher risk of treatment failure compared with TNF antagonists, particularly among patients with Crohn disease, without offering a significant safety advantage.

Dataset Information

Association Between Use of Thiopurines or Tumor Necrosis Factor Antagonists Alone or in Combination and Risk of Lymphoma in Patients With Inflammatory Bowel Disease.

Publications

Association Between Use of Thiopurines or Tumor Necrosis Factor Antagonists Alone or in Combination and Risk of Lymphoma in Patients With Inflammatory Bowel Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets