Increased risk of thiopurine‐related adverse events in elderly patients with IBD

Calafat, Margalida; Mañosa, Míriam; Cañete, Fiorella; Ricart, Elena; Iglesias, Eva; Calvo, Marta; Rodríguez-Moranta, Francisco; Taxonera, Carlos; Nos, Pilar; Mesonero, Francisco; Martín-Arranz, María-Dolores; Mínguez, Miguel; Gisbert, Javier P.; García-López, Santiago; Francisco, Ruth de; Gomollón, Fernando; Calvo, Xavier Calvet; García‐Planella, Esther; Rivero, Montserrat; Martínez-Cadilla, Jesús; Argüelles, F; Arias, Lara; Cimavilla, Marta; Zabana, Yamile; Domènech, Eugeni

doi:10.1111/apt.15458

Cited by 41 publications

(23 citation statements)

References 42 publications

(50 reference statements)

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“…An increase in CCI was associated with any infection during treatment in vedolizumab (OR 1.387, 95% CI 1.022‐1.883, P = 0.036), but not in ustekinumab‐treated patients (OR 0.998, 95% CI 0.611‐1.630, P = 0.994). While earlier studies showed an association between comorbidities and adverse events for immunomodulators, 14 this association was not found for vedolizumab or ustekinumab in our study.…”

Section: Discussioncontrasting

confidence: 99%

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Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab‐ and ustekinumab‐treated patients with inflammatory bowel disease—a prospective multicentre cohort study

Asscher

Biemans

Pierik

et al. 2020

Aliment Pharmacol Ther

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Summary Background Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD). Aims To evaluate the association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD. Methods IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid‐free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders. Results We included 203 vedolizumab‐ and 207 ustekinumab‐treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9‐104.0) and 48.4 (IQR 24.4‐55.1) weeks, median follow‐up time 104.0 (IQR 103.1‐104.0) and 52.0 weeks (IQR 49.3‐100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022‐1.883, P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127‐2.231, P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034‐2.541, P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes. Conclusions Comorbidity ‐ but not age ‐ is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients.

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Section: Discussioncontrasting

confidence: 99%

“…In immunomodulator and anti‐TNF‐treated IBD patients, an increased risk for infections in patients with comorbidities has been detected 12,13 . For thiopurine treatment, an independent association between cardiovascular risk factors and adverse events was observed 14 …”

Section: Introductionmentioning

confidence: 99%

Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab‐ and ustekinumab‐treated patients with inflammatory bowel disease—a prospective multicentre cohort study

Asscher

Biemans

Pierik

et al. 2020

Aliment Pharmacol Ther

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show abstract

“…In particular, the absolute risks were 2-fold to 3-fold greater in patients >65 years compared with younger patients [17]. Another retrospective, multicenter study [28] found that initiation of thiopurine therapy >60 years was associated with a higher risk of thiopurine-related adverse events. The efficacy and safety of vedolizumab are established in younger patients [29] and in the elderly [30].…”

Section: Discussionmentioning

confidence: 99%

Gastroenterologists’ preference and risk perception on the use of immunomodulators and biological therapies in elderly patients with ulcerative colitis: an international survey

Chan

Kariyawasam

Kim

et al. 2020

European Journal of Gastroenterology &Amp; Hepatology

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Background and aims: Comorbidities, polypharmacy, malignancies, and infections complicate management of elderly patients with inflammatory bowel diseases (IBD). This study assessed gastroenterologists’ preference in the prescription of medications or surgery to elderly patients with IBD, and the factors associated with their choices. Methods An international case-based survey was conducted that presented three cases of steroid-dependent ulcerative colitis assessing young-age versus elderly-age patients, with and without comorbidity. Physician characteristics and practice demographics were collected. Factors associated with selection of different choices of therapy were determined by logistic regression analysis. Results A total of 424 respondents from 41 countries were included. Vedolizumab (53.2%) and thiopurines (19.4%) were the top treatment preferences for moderate-to-severe ulcerative colitis (P < 0.0001). Comorbidity and older age were independently associated with more frequent use of vedolizumab (P < 0.0001), and less frequent use of immunomodulators and anti-tumour necrosis factor (TNF; P < 0.0001). Comorbidity was the only independent predictor for selecting colectomy (P < 0.0001). A history of lymphoma (94%) and opportunistic infection (78.3%) were the most frequent conditions precluding the use of thiopurine and anti-TNF in elderly patients with IBD. Only 6.1% of respondents considered patient age a limit for vedolizumab, while 37.9% considered age as a limiting factor in prescribing thiopurines (P < 0.001). Geographical heterogeneity was identified with significantly more physicians from Oceania and North America favouring the use of vedolizumab. Conclusion Vedolizumab was the preferred first-line agent in the treatment of elderly patients with IBD with steroid-dependent moderate-to-severe ulcerative colitis. Older age and presence of comorbidity influenced the selection of medication. Comorbidity was the main predictor of colectomy. Geographical heterogeneity in prescribing habits may relate to medication reimbursement in individual countries.

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“…Endoscopic remission was defined as Crohn's Disease Endoscopic Index of Severity (CDEIS) score <7 ( 22 ) or Rutgeerts score ≤i1 from a baseline Rutgeerts score ≥i2 ( 23 ). Mucosal healing (MH) was defined as the absence of ulceration at ileocolonoscopy.…”

Section: Methodsmentioning

confidence: 99%

Thalidomide Combined With Azathioprine as Induction and Maintenance Therapy for Azathioprine-Refractory Crohn's Disease Patients

Qiu

et al. 2020

Front. Med.

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The combination therapy of thalidomide and azathioprine (AZA) offers an alternative in clinical practice for Crohn's disease (CD) patients experiencing a loss of response to AZA monotherapy. However, little is known about the efficacy and safety of this combination therapy for patients with CD. This was a retrospective study of 122 consecutive CD patients who lost response to AZA therapy and had switched to a combination therapy of thalidomide and AZA. The primary outcomes were clinical response and clinical remission rates at week 24. Patients who had an initial response to combination therapy were continued on the treatment for remission maintenance. The secondary outcomes were the proportion of clinical relapse throughout maintenance. The Kaplan-Meier method was used to calculate cumulative rates, and Cox regression analysis was used for multivariate analysis. During induction, 80.3% (98/122) patients achieved clinical response within a median duration of 6.5 weeks, (interquartile range, 4.3-8.1 weeks). The rate of clinical remission at 24 weeks was 70.5%. During follow-up, 22.4% (22/98) of the patients that were maintained on combination therapy experienced clinical relapse. The proportions of patients in remission status at 12, 24, and 36 months were 85.1, 78.3, and 70.1%, respectively. Multivariate analysis revealed C-reactive protein >10 mg/L at disease relapse on AZA monotherapy [adjusted hazard ratio (HR), 4.72; 95% CI, 1.19-18.75, P = 0.027] and 6-thioguanine nucleotides level ≥235 pmol/8 × 10 8 erythrocytes at AZA monotherapy (adjusted HR, 5.32; 95% CI, 1.40-20.14, P = 0.014) were associated with disease relapse on combination therapy. The endoscopic remission rate was 63.6%. Mucosal healing was achieved in 23.6% of the patients. Both Crohn's Disease Endoscopic Index of Severity (13.4 ± 4.92 vs. 6.12 ± 5.24, P < 0.001) and Rutgeerts scores (3.23 ± 0.73 vs. 1.77 ± 1.59, P = 0.003) were significantly decreased with the use of combination therapy. Adverse events occurred in 62 (50.8%) patients, but only 13 (10.7%) necessitated therapy discontinuation. Thalidomide combined with AZA was effective in inducing clinical remission and sustaining long-term steroid-free remission in CD patients who lost response to AZA monotherapy.

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Increased risk of thiopurine‐related adverse events in elderly patients with IBD

Cited by 41 publications

References 42 publications

Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab‐ and ustekinumab‐treated patients with inflammatory bowel disease—a prospective multicentre cohort study

Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab‐ and ustekinumab‐treated patients with inflammatory bowel disease—a prospective multicentre cohort study

Gastroenterologists’ preference and risk perception on the use of immunomodulators and biological therapies in elderly patients with ulcerative colitis: an international survey

Thalidomide Combined With Azathioprine as Induction and Maintenance Therapy for Azathioprine-Refractory Crohn's Disease Patients

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