Systematic review with network meta-analysis: the efficacy of anti-TNF agents for the treatment of Crohn's disease.

BACKGROUND: Anti-tumour necrosis factor-alpha agents (anti-TNF) are effective therapies for the treatment of Crohn's disease (CD), but their comparative efficacy is unknown. AIM: To perform a network meta-analysis comparing the efficacy of anti-TNF therapies in CD. METHODS: After screening 506 studies, reviewers extracted information on 10 studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent to placebo. Bayesian network meta-analysis (NMA) was performed to compare the effects of anti-TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. RESULTS: Compared to placebo, TMA revealed that anti-TNF agents result in a higher likelihood of induction of remission and response (RR: 1.66, 95% CI: 1.17-2.36 and RR: 1.43, 95% CI: 1.17-1.73, respectively) as well as maintenance of remission and response (RR: 1.78, 95% CI: 1.51-2.09 and RR: 1.68, 95% CI: 1.46-1.93, respectively). NMA found nonsignificant trends between infliximab and adalimumab or certolizumab pegol. Among subcutaneous therapies, NMA demonstrated superiority of adalimumab to certolizumab pegol for induction of remission (RR: 2.93, 95% CrI: 1.21-7.75). Sample size calculations suggest that adequately powered head-to-head comparative efficacy trials would require greater than 3000 patients. CONCLUSIONS: All anti-TNF agents are effective for induction and maintenance of response and remission in the treatment of CD. Although adalimumab is superior to certolizumab pegol for induction of remission, there is no evidence of clinical superiority among anti-TNF agents. Head-to-head trials among the anti-TNF agents are impractical in terms of size and cost.

Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis.

BACKGROUND: Antibodies against tumour necrosis factor-alpha (anti-TNF) are effective therapies in the treatment of ulcerative colitis (UC), but their comparative efficacy is unknown. AIM: To perform a network meta-analysis comparing the efficacy of anti-TNF agents in UC. METHODS: After screening 506 studies, reviewers extracted information on seven studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent to placebo. Bayesian network meta-analysis (NMA) was performed to compare the effects of anti-TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. RESULTS: Compared to placebo, TMA revealed that anti-TNF agents result in a higher likelihood of induction of remission and response (RR: 2.45, 95% CI: 1.72-3.47 and RR: 1.65, 95% CI: 1.37-1.99 respectively) as well as maintenance of remission and response (RR: 2.00, 95% CI: 1.52-2.62 and RR: 1.76, 95% CI: 1.46-2.14 respectively). Individually, infliximab, adalimumab and goliumumab resulted in a higher likelihood of induction and maintenance for both remission and response. NMA found nonsignificant trends in comparisons of the individual agents. The required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively. CONCLUSIONS: This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis. However, network meta-analysis demonstrates that no single agent is clinically superior to the others and therefore, other factors such as cost, safety, route of administration and patient preference should dictate our choice of anti-TNF agents. A randomised comparative efficacy trial between infliximab and adalimumab in UC is of practical size and should be performed.

Cost-effectiveness analysis: cardiovascular benefits of proton pump inhibitor co-therapy in patients using aspirin for secondary prevention.

BACKGROUND: Many patients with cardiovascular (CV) disease will stop aspirin (ASA) because of ASA-related dyspepsia. Proton pump inhibitor (PPI) co-therapy may reduce ASA-related dyspepsia, enhancing ASA adherence and improving CV outcomes. AIM: To explore the impact of PPI co-therapy on CV outcomes in long-term, low-dose ASA users. METHODS: We modified a previously published Markov model to assess the long-term impact of PPI co-therapy on CV and upper gastrointestinal bleeding (UGIB) outcomes among patients using ASA for secondary CV prevention. UGIB events, recurrent myocardial infarctions (MIs) and incremental cost-effectiveness ratios (ICERs) were measured. The perspective taken was that of a long-term payer. RESULTS: Compared with ASA alone, ASA plus PPI resulted in fewer lifetime UGIB events (3.4% vs. 7.2%) and increased ASA adherence (74% vs. 71%). Increased ASA adherence resulted in fewer recurrent MIs (26 fewer events per 10000 patients). On average, the ASA plus PPI strategy resulted in 38 additional days of life per patient, with the majority of this benefit (61%) because of a reduction in CV mortality (rather than UGIB-related mortality). ASA plus PPI was also more costly than ASA alone, with an ICER of $19000 per life-year saved. Results were sensitive to cost of PPI and impact of PPI on ASA adherence. CONCLUSIONS: Proton pump inhibitor co-therapy has the potential to impact not only GI, but also CV outcomes in patients with CV disease using ASA and such co-therapy is likely to be cost-effective. Future studies should better quantify the CV benefits of PPI co-therapy.

Underutilization of gastroprotection for at-risk patients undergoing percutaneous coronary intervention: Spain compared with the United States.

BACKGROUND: Proton pump inhibitors (PPIs) are the preferred agents for the prevention of aspirin-associated upper gastrointestinal bleeding (UGIB). Data are limited to determine whether PPIs are being used to reduce UGIB risk. AIM: To evaluate the implementation of PPI treatment to reduce the GI risk in two cardiology centres from Europe and the United States. METHODS: A retrospective cross-sectional study was carried out at the University of Michigan and University Hospital-Zaragoza in 429 consecutive patients hospitalized for percutaneous coronary intervention (PCI) on dual antiplatelet therapy. RESULTS: Admission for PPI co-therapy was similar (34% vs. 30%) in both centres. At discharge, the proportion of high-risk patients receiving PPI therapy in the Spanish centre (75.4%) was higher than their American peers (55.6%) (OR: 2.5; 95% CI; 1.3-4.7). No differences in PPI prescription rates were found among Spanish patients with/without GI risk factors. The opportunity to initiate PPI co-therapy in high-risk patients was missed in 81.8% (36/44) of those not on PPI at admission in US patients vs. 24.1% (19/79) (P < 0.0001) in Spanish patients. CONCLUSIONS: There are important differences concerning PPI prescription and risk stratification in the two centres when managing PCI patients. Efforts to stratify risks and utilize appropriate strategies for UGIB prophylaxis in high-risk patients are warranted.