RESUMO
Inflammatory bowel diseases (IBD) currently impose an immense social and economic burden on society in terms of both direct and indirect healthcare costs. Their incurable and progressive nature results in an unavoidable lifetime expense. The introduction of infliximab more than two decades ago had revolutionized IBD treatment. Nowadays, while biologic drugs comprise various vital therapeutic options for patients, they can be associated to significant costs to healthcare systems. The most crucial benefit of biosimilars is that they bring more significant cost reduction and increase access to advanced therapies. They also allow the treatment of newly diagnosed patients and dose optimization for those who need it. There is an inverse relationship between price and demand for treatment with biologics. For a more significant reduction in cost to be possible, greater use of biosimilars is necessary. For this to occur, it is imperative not only to use biosimilars in naïve patients but also to switch to biosimilars in those patients who have started therapy with reference biologics. At present, randomized and observational studies have demonstrated effectiveness and safety results in recommending a single switch between a reference product and a biosimilar, and vice versa. The purpose of this manuscript is to review the literature and discuss whether scientific evidence is enough to support multiple switches of biologics and biosimilars in IBD patients.
Assuntos
Medicamentos Biossimilares , Substituição de Medicamentos , Doenças Inflamatórias Intestinais , Medicamentos Biossimilares/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Produtos Biológicos/uso terapêuticoRESUMO
ABSTRACT Inflammatory bowel diseases (IBD) currently impose an immense social and economic burden on society in terms of both direct and indirect healthcare costs. Their incurable and progressive nature results in an unavoidable lifetime expense. The introduction of infliximab more than two decades ago had revolutionized IBD treatment. Nowadays, while biologic drugs comprise various vital therapeutic options for patients, they can be associated to significant costs to healthcare systems. The most crucial benefit of biosimilars is that they bring more significant cost reduction and increase access to advanced therapies. They also allow the treatment of newly diagnosed patients and dose optimization for those who need it. There is an inverse relationship between price and demand for treatment with biologics. For a more significant reduction in cost to be possible, greater use of biosimilars is necessary. For this to occur, it is imperative not only to use biosimilars in naïve patients but also to switch to biosimilars in those patients who have started therapy with reference biologics. At present, randomized and observational studies have demonstrated effectiveness and safety results in recommending a single switch between a reference product and a biosimilar, and vice versa. The purpose of this manuscript is to review the literature and discuss whether scientific evidence is enough to support multiple switches of biologics and biosimilars in IBD patients.
RESUMO
BACKGROUND: In the context of an ageing inflammatory bowel disease (IBD) population, cardiovascular comorbidities become particularly relevant. Novel small molecule drugs (SMDs) for the treatment of moderate-to-severe IBD have been recently approved, including Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor (S1P) modulators. Data from rheumatoid arthritis population have raised concerns about the risk of cardiovascular events with the use of tofacitinib, which was extrapolated to other immune-mediated diseases and other JAK inhibitors. S1P receptor modulation has been associated with potential cardiovascular events, especially bradycardia and cardiac conduction abnormalities. AIM: To review the incidence of cardiovascular events with the use of SMDs in patients with IBD and to provide practical recommendations on mitigation strategies. METHODS: Published literature was reviewed; recommendations were synthesised by experts in both cardiovascular diseases and IBD. RESULTS: Evidence from the IBD population does not indicate a higher risk of cardiovascular events with tofacitinib and other JAK inhibitors. The risk is higher in patients with intermediate to high cardiovascular risk. S1P modulators may be associated with a dose-dependent, first-dose effect, transient risk of conduction abnormalities (bradycardia and AV block). Screening and monitoring of cardiovascular risk factors should be done in all patients with IBD. Risk stratification for cardiovascular disease should be performed before starting treatment with SMDs. CONCLUSIONS: Available evidence of both JAK inhibitors and S1P modulators indicates a reassuring safety profile of SMDs from the cardiovascular perspective in the overall IBD population. Efforts should be made to identify patients with IBD at a higher risk of cardiovascular events.
Assuntos
Artrite Reumatoide , Doenças Inflamatórias Intestinais , Inibidores de Janus Quinases , Humanos , Inibidores de Janus Quinases/uso terapêutico , Bradicardia/tratamento farmacológico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Pirróis/efeitos adversosRESUMO
BACKGROUND AND AIMS: Advanced therapies for inflammatory bowel disease [IBD] could potentially lead to a state of immunosuppression with an increased risk of opportunistic infections [OIs]. We aimed to provide an update on the incidence of OIs among adult IBD patients in randomized controlled trials [RCTs] of approved biologics and small-molecule drugs [SMDs]. Also, we aimed to describe OI definitions utilized in RCTs, to ultimately propose a standardized definition. METHODS: Electronic databases were searched from January 1, 1990, until April 16, 2022. Our primary outcome was incidence rate of overall OIs among IBD patients exposed and unexposed to biologics or SMDs. We also describe specific OIs reported in included trials, as well as definitions of OIs within studies when provided. RESULTS: Ninety studies were included. The incidence rates of reported OIs were 0.42 and 0.21 per 100 person-years in patients exposed to advanced therapies and placebo, respectively. This was highest for anti-tumour necrosis factors [0.83 per 100 person-years] and Janus kinase inhibitors [0.55 per 100 person-years] and lowest for anti-integrins and ozanimod. On meta-analysis, no increased risk of OIs was observed. None of the studies provided a detailed definition of OIs, or a comprehensive list of infections considered as OIs. CONCLUSION: Different mechanisms of action may have specific OI profiles. In the absence of a uniform definition of OIs, these estimates are less reliable. We propose a definition to be used in future studies to help provide standardized reporting. When using this definition, we saw significant differences in incidence rates of OIs across mechanisms of action.
Assuntos
Doenças Inflamatórias Intestinais , Infecções Oportunistas , Adulto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/etiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , IncidênciaRESUMO
BACKGROUND: There is a growing armamentarium for the treatment of moderate-to-severe ulcerative colitis. We aimed to compare the relative efficacy and safety of biologics and small molecule drugs for the treatment of patients with moderate-to-severe ulcerative colitis. METHODS: In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials without language restrictions for articles published between Jan 1, 1990, and July 1, 2021. Major congresses' databases from Jan 1, 2018, to July 3, 2021, were reviewed manually. Phase 3, placebo-controlled or head-to-head randomised controlled trials (RCTs) assessing the efficacy and safety of biologics or small molecule drugs as induction or maintenance therapies for patients with moderate-to-severe ulcerative colitis were included. Phase 2 RCTs were excluded because of their small sample sizes and inclusion of doses not further explored in phase 3 RCTs. Summary data from intention-to-treat analyses were extracted from included reports by JSL and PAO. The primary outcome was the induction of clinical remission. A network meta-analysis was done under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. The surface under the cumulative ranking (SUCRA) was used to rank the included agents for each outcome. Higher SUCRA scores correlate with better efficacy, whereas lower SUCRA scores correlate with better safety. Maintenance data on efficacy for treat-straight-through and randomised responder trials are also presented. This study is registered with PROSPERO, CRD42021225329. FINDINGS: Our search yielded 5904 results, from which 29 studies (four being head-to-head RCTs) fulfilled our inclusion criteria and were included. Of these, 23 studies assessed induction therapy with either a biologic or small molecule drug, comprising 10 061 patients with ulcerative colitis. A risk of bias assessment showed a low risk of bias for most of the included studies. Upadacitinib was significantly superior to all other interventions for the induction of clinical remission (infliximab [OR 2·70, 95% CI 1·18-6·20], adalimumab [4·64, 2·47-8·71], golimumab [3·00, 1·32-6·82], vedolizumab [3·56, 1·84-6·91], ustekinumab [2·92, 1·31-6·51], etrolizumab [4·91, 2·59-9·31], tofacitinib [2·84, 1·28-6·31], filgotinib 100 mg [6·15, 2·98-12·72], filgotinib 200 mg [4·49, 2·18-9·24], and ozanimod (2·70, 1·18-6·20), and ranked highest for the induction of clinical remission (SUCRA 0·996). No differences between active interventions were observed when assessing adverse events and serious adverse events. Vedolizumab ranked lowest for both adverse events (SUCRA 0·184) and serious adverse events (0·139), whereas upadacitinib ranked highest for adverse events (0·843) and ozanimod ranked highest for serious adverse events (0·831). INTERPRETATION: Upadacitinib was the best performing agent for the induction of clinical remission (the primary outcome) but the worst performing agent in terms of adverse events in patients with moderate-to-severe ulcerative colitis. Vedolizumab was the best performing agent for safety outcomes. With the paucity of direct comparisons in the published literature, our results might help clinicians to position drugs in treatment algorithms. FUNDING: None.
Assuntos
Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Humanos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Etrolizumab is a gut-targeted, anti-ß7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. METHODS: HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18-80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov, NCT02100696. FINDINGS: HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). INTERPRETATION: HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. FUNDING: F Hoffmann-La Roche.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Ásia , Europa (Continente) , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Oriente Médio , América do Norte , Oceania , Indução de Remissão , Índice de Gravidade de Doença , América do Sul , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Adulto JovemRESUMO
Despite significant development in the pharmacological treatment of inflammatory bowel diseases (IBD) along with the evolution of therapeutic targets and treatment strategies, a significant subset of patients still requires surgery during the course of the disease. As IBD patients are frequently exposed to biologics at the time of abdominal and perianal surgery, it is crucial to identify any potential impact of biological agents in the perioperative period. Even though detectable serum concentrations of biologics do not seem to increase postoperative complications after abdominal procedures in IBD, there is increasing evidence on the role of therapeutic drug monitoring (TDM) in the perioperative setting. This review aims to provide a comprehensive summary of published studies reporting the association of drug concentrations and postoperative outcomes, postoperative recurrence (POR) after an ileocolonic resection for Crohn's disease (CD), colectomy rates in ulcerative colitis (UC), and perianal fistulizing CD outcomes in patients treated with biologics. Current data suggest that serum concentrations of biologics are not associated with an increased risk in postoperative complications following abdominal procedures in IBD. Moreover, higher concentrations of anti-TNF agents are associated with a reduction in colectomy rates in UC. Finally, higher serum drug concentrations are associated with reduced rates of POR after ileocolonic resections and increased rates of perianal fistula healing in CD. TDM is being increasingly used to guide clinical decision making with favorable outcomes in many clinical scenarios. However, given the lack of high quality data deriving mostly from retrospective studies, the evidence supporting the systematic application of TDM in the perioperative setting is still inconclusive.
RESUMO
Over time, clinicians have become increasingly comfortable embracing the prescription of biosimilars-highly similar versions of innovator or reference biological agents-for their patients with inflammatory diseases. Although a switch from a reference product to a licensed biosimilar version (or vice versa) is a medical decision robustly supported by the stepwise accumulation of clinical trial evidence concerning comparable safety, immunogenicity, and efficacy between these products, a switch from one biosimilar to another biosimilar of the same reference product, or a cross-switch, is not. Similarity among biosimilars of a reference product is not a regulatory agency concern and therefore is unlikely to be investigated in randomized controlled trials in the foreseeable future. Yet in clinical practice, across a diverse range of patients, the option to cross-switch from one biosimilar to another can and does arise for valid reasons such as convenience or tolerability issues, or driven by third parties (e.g., payers). In the absence of clinical trial data, clinicians must attempt to objectively evaluate the emerging real-world cross-switching evidence within the context of what is known about the science underpinning a designation of biosimilar. That knowledge then needs to be integrated with what clinicians know about their patients and their disease on a case-by-case basis. This review aims to consolidate relevant emerging real-world data and other key information about biosimilar-to-biosimilar cross-switching for prescribing clinicians. In the absence of clear clinical guidelines addressing this topic at present, this review may serve to facilitate discretionary and educated treatment decision making.
Assuntos
Produtos Biológicos/administração & dosagem , Medicamentos Biossimilares/administração & dosagem , Substituição de Medicamentos , Animais , Produtos Biológicos/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Tomada de Decisões , Humanos , Padrões de Prática Médica/tendências , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. Therapies for IBD have the potential to modulate this risk. The aims of this Evidence-Based Guideline were to summarize available evidence and to provide practical recommendations regarding epidemiological aspects, prevention and drug-related risks of venous and arterial thrombotic events in patients with IBD. A virtual meeting took place in May 2020 involving 14 international IBD experts and 3 thrombosis experts from 12 countries. Proposed statements were voted upon in an anonymous manner. Agreement was defined as at least 75% of participants voting as 'fully agree' or 'mostly agree' with each statement. For each statement, the level of evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading system. Consensus was reached for 19 statements. Patients with IBD harbour an increased risk of venous and arterial thrombotic events. Thromboprophylaxis is indicated during hospitalization of any cause in patients with IBD. Disease activity is a modifiable risk factor in patients with IBD, and physicians should aim to achieve deep remission to reduce the risk. Exposure to steroids should be limited. Antitumour necrosis factor agents might be associated with a reduced risk of thrombotic events.
Assuntos
Anti-Inflamatórios/uso terapêutico , Fibrinolíticos/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Trombose/prevenção & controle , Anti-Inflamatórios/efeitos adversos , Hospitalização , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/fisiopatologia , Cooperação Internacional , Gravidade do Paciente , Medição de Risco , Fatores de Risco , Trombose/diagnóstico , Trombose/etiologia , Trombose/fisiopatologiaRESUMO
BACKGROUND: In this analysis we aimed to describe Brazilian inflammatory bowel disease (IBD) patients' knowledge and perceptions regarding biosimilars and compare with viewpoints from non-Brazilian patients. METHODS: An online survey consisting of 19 questions was made available by the European Federation of Crohn's and Ulcerative Colitis Associations between July 2018 and December 2018. Only respondents who had heard of biosimilars were asked to respond to all of the questions. RESULTS: A total of 102 Brazilian IBD patients responded to the survey. The majority (78.4%) of patients had been exposed to anti-tumor-necrosis-factor drugs and 63.4% of them had heard of biosimilars. Brazilian respondents worried significantly more about biosimilars being less effective than the originator (62.5% versus 47.9%, p value 0.03) and molecular differences between biosimilars and originators (53.1% versus 31.8, p value 0.001) as compared with non-Brazilian IBD patients. The majority of Brazilian (75%) and non-Brazilian (64.1%) respondents thought that the lower cost of biosimilars should not come before their safety and efficacy (p value 0.09). In addition, 79.1% of Brazilian respondents believed that the arrival of biosimilars will have an impact on the management of IBD. CONCLUSIONS: Brazilian patients reported higher rates of misconceptions regarding biosimilars than non-Brazilian IBD patients. Although patients still worry about different aspects regarding biosimilars, they also tend to be confident that biosimilars will have an impact on the management of their disease. With the recent approval of many biosimilars in Brazil and the imminent widespread use of these drugs, our data raise awareness for the need of providing patient education to prevent negative expectations toward switching to biosimilars.
RESUMO
INTRODUCTION: Sphingosine-1-phosphate modulators are approved for the treatment of multiple sclerosis and are under development for other immune-mediated conditions; however, safety concerns have arisen. OBJECTIVE: The objective of this systematic review was to investigate the safety profile of S1P modulators in patients with multiple sclerosis, ulcerative colitis, Crohn's disease, psoriasis, and systemic lupus erythematosus. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1 January, 1990 through 1 April, 2020. We also performed a manual review of conference databases from 2017 through 2020. The primary outcome was the occurrence of adverse events and serious adverse events. We also estimated the occurrence of serious infections, herpes zoster infection, malignancy, bradycardia, atrio-ventricular block, and macular edema. We performed a meta-analysis of controlled studies to assess the risks of such events. RESULTS: We identified 3843 citations; of these, 26 studies were finally included, comprising 9604 patients who were exposed to a sphingosine-1-phosphate modulator. A meta-analysis of randomized controlled trials showed an increased risk in herpes zoster infection [risk ratio, 1.75 (95% confidence interval 1.09-2.80)], bradycardia [2.64 (1.77-3.96)], and atrio-ventricular block [1.73 (1.03-2.91)] among subjects exposed to sphingosine-1-phosphate modulators as compared with a placebo or an active comparator. CONCLUSIONS: We found an increased risk of herpes zoster infection, and transient cardiovascular events among patients treated with sphingosine-1-phosphate modulators. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42020172575.
Assuntos
Doença de Crohn , Herpes Zoster , Esclerose Múltipla , Psoríase , Bradicardia , Herpes Zoster/induzido quimicamente , Humanos , Esclerose Múltipla/tratamento farmacológico , Psoríase/tratamento farmacológicoRESUMO
METHODS: A multicenter cross-sectional study involving seven referral centers from three cities of Argentina was undertaken. Patients with a diagnosis of ulcerative colitis (UC), Crohn's disease (CD), or indeterminate colitis (IBDU/IC) were invited to answer an anonymous survey, which included a 5-point Likert scale to evaluate adherence to therapies. Independent variables associated with inadequate adherence were evaluated. RESULTS: Overall, 447 UC/IBDU and 135 CD patients were enrolled. Median age was 37 years (range 21-72); 39.8% were male; median time from diagnosis was 6 years (0.5-35). 91.4% were under treatment with at least one oral medication; 50.3% of patients reported inadequate adherence to oral medications. Patients with UC/IBDU had a lower risk of inadequate adherence when compared to patients with CD (OR 0.57 (0.37-0.87)). 21.8% reported inadequate adherence to biologics; subcutaneous administration was significantly associated with inadequate adherence to biologics (OR 4.8 (1.57-14.66)). CONCLUSION: Inadequate treatment adherence is common among patients with IBD, and potentially modifiable factors were identified.
RESUMO
Introduction: Sphingosine-1-phosphate (S1P) is a membrane-derived lysophospholipid signaling molecule implicated in various physiological and pathological processes, such as regulation of the immune, cardiovascular, pulmonary, and nervous systems and theoretical cancer-related risks, through extracellular activation of S1P1-5 receptors.Areas covered: S1P receptor agonism is a novel strategy for the treatment of UC targeting lymphocyte recirculation, through blockade of lymphocyte egress from lymph nodes. We conducted an extensive literature review on PUBMED on currently available data on molecular aspects of S1P modulation, the mechanisms of action of S1PR agonists (fingolimod, ozanimod, etrasimod, and KRP-203), and their potential efficacy and safety for the treatment of patients with ulcerative colitis.Expert opinion: Selective S1P modulators have emerged to enlarge the efficacy and safety profile of this class of agents. Phase 3 programs should add the potential body of evidence to prove their benefit for the management of UC patients.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Receptores de Esfingosina-1-Fosfato/agonistas , Acetatos/uso terapêutico , Ensaios Clínicos como Assunto , Colite Ulcerativa/patologia , Humanos , Indanos/uso terapêutico , Indóis/uso terapêutico , Lisofosfolipídeos/metabolismo , Oxidiazóis/uso terapêutico , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
BACKGROUND & AIMS: Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases and other immune-mediated diseases. Tofacitinib is effective in treatment of ulcerative colitis, but there are safety concerns. We performed a systematic review and meta-analysis to investigate the safety profile of tofacitinib, upadacitinib, filgotinib, and baricitinib in patients with rheumatoid arthritis, inflammatory bowel diseases, psoriasis, or ankylosing spondylitis. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1, 1990, through July 1, 2019. We performed a manual review of conference databases from 2012 through 2018. The primary outcome was incidence rates of adverse events (AEs) and serious AEs. We also estimated incidence rates of serious infections, herpes zoster infection, non-melanoma skin cancer, other malignancies, major cardiovascular events, venous thromboembolism, and mortality. We performed a meta-analysis, which included controlled studies, to assess the relative risk of these events. RESULTS: We identified 973 studies; of these, 82 were included in the final analysis, comprising 66,159 patients with immune-mediated diseases who were exposed to a JAK inhibitor. Two-thirds of the included studies were randomized controlled trials. The incidence rate of AEs was 42.65 per 100 person-years and of serious AEs was 9.88 per 100 person-years. Incidence rates of serious infections, herpes zoster infection, malignancy, and major cardiovascular events were 2.81 per 100 person-years, 2.67 per 100 person-years, 0.89 per 100 person-years, and 0.48 per 100 person-years, respectively. Mortality was not increased in patients treated with JAK inhibitors compared with patients given placebo or active comparator (relative risk 0.72; 95% confidence interval 0.40-1.28). The meta-analysis showed a significant increase in risk of herpes zoster infection among patients who received JAK inhibitors (relative risk 1.57; 95% confidence interval 1.04-2.37). CONCLUSIONS: In a systematic review and meta-analysis, we found an increased risk of herpes zoster infection among patients with immune-mediated diseases treated with JAK inhibitors. All other AEs were not increased among patients treated with JAK inhibitors.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Herpes Zoster/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores de Janus Quinases/efeitos adversos , Psoríase/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Artrite Reumatoide/imunologia , Artrite Reumatoide/mortalidade , Azetidinas/efeitos adversos , Herpes Zoster/induzido quimicamente , Herpes Zoster/imunologia , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Incidência , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/mortalidade , Inibidores de Janus Quinases/administração & dosagem , Janus Quinases/antagonistas & inibidores , Janus Quinases/imunologia , Janus Quinases/metabolismo , Piperidinas/efeitos adversos , Placebos/administração & dosagem , Placebos/efeitos adversos , Psoríase/imunologia , Psoríase/mortalidade , Purinas , Pirazóis , Piridinas/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Espondilite Anquilosante/imunologia , Espondilite Anquilosante/mortalidade , Sulfonamidas/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento , Triazóis/efeitos adversosRESUMO
Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition. Previously, the focus has been on extraintestinal manifestations of IBD, including arthritis, psoriasis, and uveitis. Although comorbidities have long been the subject of intensive research in other chronic inflammatory diseases such as rheumatoid arthritis, the concept of comorbidities is only beginning to emerge in IBD. Several comorbid conditions have been proposed to be related to IBD, including cardiovascular disease, neuropsychological disorders, and metabolic syndrome. Recognition of these conditions and their treatment could lead to better management of IBD. This Review aims to explore current knowledge regarding classic and emerging comorbidities related to IBD.
Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Síndrome Metabólica/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Comorbidade , Fadiga/epidemiologia , Humanos , Estilo de Vida , Adesão à Medicação , Osteoporose/epidemiologia , Prevalência , Saúde Reprodutiva , Saúde Sexual , Resultado do TratamentoRESUMO
Big data methodologies, made possible with the increasing generation and availability of digital data and enhanced analytical capabilities, have produced new insights to improve outcomes in many disciplines. Application of big data in the health-care sector is in its early stages, although the potential for leveraging underutilized data to gain a better understanding of disease and improve quality of care is enormous. Owing to the intrinsic characteristics of inflammatory bowel disease (IBD) and the management dilemmas that it imposes, the implementation of big data research strategies not only can complement current research efforts but also could represent the only way to disentangle the complexity of the disease. In this Review, we explore important potential applications of big data in IBD research, including predictive models of disease course and response to therapy, characterization of disease heterogeneity, drug safety and development, precision medicine and cost-effectiveness of care. We also discuss the strengths and limitations of potential data sources that big data analytics could draw from in the field of IBD, including electronic health records, clinical trial data, e-health applications and genomic, transcriptomic, proteomic, metabolomic and microbiomic data.
Assuntos
Big Data , Doenças Inflamatórias Intestinais , Tomada de Decisão Clínica/métodos , Análise Custo-Benefício , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/economia , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/terapia , Medicina de Precisão/economia , Medicina de Precisão/métodos , Prognóstico , Estados UnidosRESUMO
BACKGROUND: Biologics against tumor necrosis factor (anti-TNF) have dramatically changed the management of moderate-to-severe ulcerative colitis (UC). In pivotal clinical trials, golimumab showed efficacy as induction and maintenance therapy in anti-TNF naïve UC patients. However, confirmatory data on effectiveness in the real world setting are needed. AIM: to summarize recent evidence on the effectiveness of golimumab in observational real-world studies. METHODS: A literature search was conducted using Medline, Embase, and congresses databases for English language articles or abstracts on the effectiveness of golimumab published between January 1, 2014 and May 15, 2018. Pooled short-term (6-14 weeks) and mid- and long-term (24-54 weeks) clinical response and remission rates were calculated. RESULTS: 24 abstracts were included; of those 8 were published full-text articles and 16 were abstracts from medical conferences. Overall, pooled short-term clinical response and remission rates were 59.3% (range 35-85.5%; 13 studies; 1429 patients) and 35.9% (range 14-51.7%; 9 studies; 666 patients), respectively. Pooled mid- and long-term clinical response and remission rates were 60.3% (range 37.1-89.5%; 4 studies; 356 patients) and 39.2% (range 12-84%; 8 studies; 822 patients), respectively. CONCLUSIONS: Results: of observational studies confirm that golimumab is an effective therapy for UC in clinical practice.