FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3147704837> ?p ?o ?g. }

• W3147704837 endingPage "21" @default.
• W3147704837 startingPage "20" @default.
• W3147704837 abstract "The number of therapies available for the treatment of inflammatory bowel disease (IBD) has increased over the last two decades. Understanding the safety and side effects of these medications is pivotal to an informed therapeutic decision for patients.1 The safety profile of medications has been shown to be a significant factor for patients when choosing appropriate IBD therapies; however, currently there is a lack of comparative safety data between various IBD therapies including thiopurines, biological agents, and tofacitinib.2 Over 50 years of global experience with the use of thiopurines has led to a substantial understanding of its safety profile. Between 15% and 40% of patients who use thiopurines develop adverse events that lead to dose reduction or drug withdrawal, and these can be idiosyncratic or dose-dependent adverse events.3 Idiosyncratic reactions include gastrointestinal disturbance (such as nausea and vomiting), malaise, headache, stomatitis, alopecia, and rash.3 Thiopurine-induced pancreatitis occurs in up to 4% of patients, particularly during the first weeks of treatment.4 Myelotoxicity is a dose-dependent adverse event that is more frequent during the first months of treatment, and the incidence rate of thiopurine-induced myelotoxicity is 3 per 100 person-years (95% confidence interval [CI]: 3%–4%).5 Thiopurines are also associated with an increased risk of malignancies. A recent nationwide cohort study that included 189 289 patients demonstrated that thiopurine use was associated with an increased risk of lymphoma (adjusted hazard ratio [HR], 2.6; 95% CI: 1.96–3.44, P < 0.001).6 Also, the CESAME study group showed that in 19 486 patients with IBD, there was an increased risk of non-melanoma skin cancers in patients using thiopurines (HR: 5.9; 95% CI: 2.1–16.4, P = 0.0006) and in previous thiopurine users (HR: 3.9; 95% CI: 1.3–12.1, P = 0.02).7 The use of anti-tumor necrosis factor (TNF)α therapy for IBD has increased over the last two decades; however, safety concerns have arisen about its use in combination with a thiopurine. A large, nationwide, population-based study of 190 694 patients with IBD found that compared with thiopurine monotherapy, anti-TNFα monotherapy was associated with increased risks of serious infection (HR, 1.71; 95% CI: 1.56–1.88), mycobacterial infection (HR, 1.98; 95% CI: 1.15–3.40), and bacterial infection (HR, 2.38; 95% CI: 1.23–4.58).8 This study also found that combination therapy with a thiopurine was associated with increased risks of serious infection (HR, 1.23; 95% CI: 1.05–1.45) and opportunistic infection (HR, 1.96; 95% CI: 1.32–2.91) compared with anti-TNFα monotherapy.8 Lymphoma risk has also been shown to be increased in patients using anti-TNFα monotherapy (HR, 2.41; 95% CI: 1.60–3.64; P < 0.001); however, the risk increases further for patients using combination therapy with a thiopurine (HR, 6.11; 95% CI: 3.46–10.8; P < 0.001).6 Vedolizumab is an anti-integrin that has been available in the management of IBD for over 5 years. Integrated safety data from vedolizumab trials (with 4811 patient-years of vedolizumab exposure) found no increased risk of any infection associated with vedolizumab exposure.9 Also, the rate of malignancy (0.1/100 person-years) was consistent with the non-exposed IBD population.9 The VARSITY study is the only head-to-head comparison between biological agents (vedolizumab and adalimumab), and this study found that the incidence rates of infections and serious infections occurred less frequently with vedolizumab than adalimumab (infections, 23.4 vs 34.6 events per 100 patient-years; serious infections, 1.6 vs 2.2 events per 100 patient-years).10 More recent real-world studies have also found that vedolizumab is associated with lower rates of serious infections and serious adverse events compared with anti-TNFα agents.11 The first integrated safety analysis of ustekinumab data from 12 registration randomized controlled trials found a favorable and consistent safety profile across registration trials.12 Ustekinumab was comparable with placebo in terms of adverse events or infections.12 However, the real-world PSOLAR study found that the cumulative incidence rates of serious infections for patients with IBD were higher than the total PSOLAR population.13 There was no increased risk of malignancy with ustekinumab.13 Tofacitinib is the first oral small molecule agent that has become available in the treatment of ulcerative colitis. In the maintenance cohort of the OCTAVE study, serious adverse events were similar between the placebo and the treatment arms; however, a statistically higher incidence rate of herpes zoster infection was observed in the tofacitinib 10 mg twice daily arm (incidence rate 6.6; 95% CI: 3.2–12.2) compared with placebo.14 Examination of phase 2 and 3 clinical trials of tofacitinib in ulcerative colitis (UC) also found dose-dependent increases in total lipid levels in patients given tofacitinib compared with placebo.15 No direct comparative safety data are available between IBD therapies. Most studies compare therapies against placebo; however, very few studies have compared different agents directly. In a network meta-analysis that compared the efficacy and safety of infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, and fecal microbiota transplantation against placebo in UC, only infliximab was associated with significantly higher occurrence of adverse events (relative risk [RR] = 1.15; 95% CI: 1.10–1.30).16 On indirect comparison, the use of vedolizumab resulted in fewer adverse events than infliximab (RR = 0.79; 95% CI: 0.62–0.94).16 In the absence of a large amount of comparative safety data between the different IBD therapies, it appears that vedolizumab and ustekinumab have the strongest safety profile, particularly relating to infection and malignancy risks.1 Anti-TNFα therapy and thiopurines are associated with increased risks of infections and certain malignancies, and combination therapy increases these risks even further. Tofacitinib is relatively new, and long-term safety data are required to fully understand its safety profile. Further comparative studies are required to substantiate current network meta-analysis results. Dr Aviv Pudipeddi has no conflicts of interests to declare. Funded through an unrestricted educational grant from Takeda Pharmaceuticals Pty Ltd." @default.
• W3147704837 created "2021-04-13" @default.
• W3147704837 creator A5078747161 @default.
• W3147704837 date "2021-04-01" @default.
• W3147704837 modified "2023-10-17" @default.
• W3147704837 title "Safety comparison of therapies used in inflammatory bowel disease" @default.
• W3147704837 cites W2024763754 @default.
• W3147704837 cites W2035746880 @default.
• W3147704837 cites W2088315857 @default.
• W3147704837 cites W2301614008 @default.
• W3147704837 cites W2611548364 @default.
• W3147704837 cites W2767910653 @default.
• W3147704837 cites W2775034276 @default.
• W3147704837 cites W2797152839 @default.
• W3147704837 cites W2800671323 @default.
• W3147704837 cites W2891310668 @default.
• W3147704837 cites W2897263984 @default.
• W3147704837 cites W2911723829 @default.
• W3147704837 cites W2944352931 @default.
• W3147704837 cites W2976731348 @default.
• W3147704837 doi "https://doi.org/10.1111/jgh.15453" @default.
• W3147704837 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33817854" @default.
• W3147704837 hasPublicationYear "2021" @default.
• W3147704837 type Work @default.
• W3147704837 sameAs 3147704837 @default.
• W3147704837 citedByCount "1" @default.
• W3147704837 countsByYear W31477048372022 @default.
• W3147704837 crossrefType "journal-article" @default.
• W3147704837 hasAuthorship W3147704837A5078747161 @default.
• W3147704837 hasBestOaLocation W31477048371 @default.
• W3147704837 hasConcept C126322002 @default.
• W3147704837 hasConcept C197934379 @default.
• W3147704837 hasConcept C207103383 @default.
• W3147704837 hasConcept C2778260677 @default.
• W3147704837 hasConcept C2778570526 @default.
• W3147704837 hasConcept C2779134260 @default.
• W3147704837 hasConcept C2780580376 @default.
• W3147704837 hasConcept C44249647 @default.
• W3147704837 hasConcept C70917649 @default.
• W3147704837 hasConcept C71924100 @default.
• W3147704837 hasConceptScore W3147704837C126322002 @default.
• W3147704837 hasConceptScore W3147704837C197934379 @default.
• W3147704837 hasConceptScore W3147704837C207103383 @default.
• W3147704837 hasConceptScore W3147704837C2778260677 @default.
• W3147704837 hasConceptScore W3147704837C2778570526 @default.
• W3147704837 hasConceptScore W3147704837C2779134260 @default.
• W3147704837 hasConceptScore W3147704837C2780580376 @default.
• W3147704837 hasConceptScore W3147704837C44249647 @default.
• W3147704837 hasConceptScore W3147704837C70917649 @default.
• W3147704837 hasConceptScore W3147704837C71924100 @default.
• W3147704837 hasIssue "S1" @default.
• W3147704837 hasLocation W31477048371 @default.
• W3147704837 hasOpenAccess W3147704837 @default.
• W3147704837 hasPrimaryLocation W31477048371 @default.
• W3147704837 hasRelatedWork W2013753126 @default.
• W3147704837 hasRelatedWork W2045364602 @default.
• W3147704837 hasRelatedWork W2089483435 @default.
• W3147704837 hasRelatedWork W2106159140 @default.
• W3147704837 hasRelatedWork W2316734434 @default.
• W3147704837 hasRelatedWork W2350328551 @default.
• W3147704837 hasRelatedWork W2781372331 @default.
• W3147704837 hasRelatedWork W3023349297 @default.
• W3147704837 hasRelatedWork W3035763496 @default.
• W3147704837 hasRelatedWork W4313236518 @default.
• W3147704837 hasVolume "36" @default.
• W3147704837 isParatext "false" @default.
• W3147704837 isRetracted "false" @default.
• W3147704837 magId "3147704837" @default.
• W3147704837 workType "article" @default.