Revisión sistemática

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Benefit-Risk of Therapies for Relapsing-Remitting Multiple Sclerosis: Testing the Number Needed to Treat to Benefit (NNTB), Number Needed to Treat to Harm (NNTH) and the Likelihood to be Helped or Harmed (LHH): A Systematic Review and Meta-Analysis.

Año 2016
Autores Mendes D , Alves C , Batel-Marques F
Revista CNS drugs
Enlaces DOI , Pubmed

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OBJECTIVE:

This study aimed to test the number needed to treat to benefit (NNTB) and to harm (NNTH), and the likelihood to be helped or harmed (LHH) when assessing benefits, risks, and benefit-risk ratios of disease-modifying treatments (DMTs) approved for relapsing-remitting multiple sclerosis (RRMS).

METHODS:

In May 2016, we conducted a systematic review using the PubMed and Cochrane Central Register of Controlled Trials databases to identify phase III, randomized controlled trials with a duration of ≥2 years that assessed first-line (dimethyl fumarate [DMF], glatiramer acetate [GA], β-interferons [IFN], and teriflunomide) or second-line (alemtuzumab, fingolimod, and natalizumab) DMTs in patients with RRMS. Meta-analyses were performed to estimate relative risks (RRs) on annualized relapse rate (ARR), proportion of relapse-free patients (PPR-F), disability progression (PP-F-CDPS3M), and safety outcomes. NNTB and NNTH values were calculated applying RRs to control event rates. LHH was calculated as NNTH/NNTB ratio.

RESULTS:

The lowest NNTBs on ARR, PPR-F, and PP-F-CDPS3M were found with IFN-β-1a-SC (NNTB 3, 95 % CI 2-4; NNTB 7, 95 % CI 4-18; NNTB 4, 95 % CI 3-7, respectively) and natalizumab (NNTB 2, 95 % CI 2-3; NNTB 4, 95 % CI 3-6; NNTB 9, 95 % CI 6-19, respectively). The lowest NNTH on adverse events leading to treatment discontinuation was found with IFN-β-1b (NNTH 14, 95 % 2-426) versus placebo; a protective effect was noted with alemtuzumab versus IFN-β-1a-SC (NNTB 22, 95 % 17-41). LHHs >1 were more frequent with IFN-β-1a-SC and natalizumab.

CONCLUSIONS:

These metrics may be valuable for benefit-risk assessments, as they reflect baseline risks and are easily interpreted. Before making treatment decisions, clinicians must acknowledge that a higher RR reduction with drug A as compared with drug B (versus a common comparator in trial A and trial B, respectively) does not necessarily mean that the number of patients needed to be treated for one patient to encounter one aditional outcome of interest over a defined period of time is lower with drug A than with drug B. Overall, IFN-β-1a-SC and natalizumab seem to have the most favorable benefit-risk ratios among first- and second-line DMTs, respectively.

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Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis.

Año 2011
Revista The American journal of gastroenterology
Enlaces DOI , Pubmed

Este artículo está incluido en 1 Resumen estructurado de revisiones sistemáticas 28 Resúmenes estructurados de revisiones sistemáticas (1 referencia)

Este artículo incluye 27 Estudios primarios 28 Estudios primarios (27 referencias)

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OBJECTIVES:

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory disorders of the gastrointestinal tract of unknown etiology. Evidence for treatment of the condition with biological therapies exists, but no systematic review and meta-analysis has examined this issue in its entirety.

METHODS:

MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to December 2010). Trials recruiting adults with active or quiescent CD or UC and comparing biological therapies (anti-tumor necrosis factor-α (TNFα) antibodies or natalizumab) with placebo were eligible. Dichotomous symptom data were pooled to obtain relative risk (RR) of failure to achieve remission in active disease and RR of relapse of activity in quiescent disease once remission had occurred, with a 95% confidence interval (CI).

RESULTS:

The search strategy identified 3,061 citations, 27 of which were eligible. Anti-TNFα antibodies and natalizumab were both superior to placebo in inducing remission of luminal CD (RR of no remission=0.87; 95% CI 0.80-0.94 and RR=0.88; 95% CI 0.83-0.94, respectively). Anti-TNFα antibodies were also superior to placebo in preventing relapse of luminal CD (RR of relapse=0.71; 95% CI 0.65-0.76). Infliximab was superior to placebo in inducing remission of moderate to severely active UC (RR=0.72; 95% CI 0.57-0.91).

CONCLUSIONS:

Biological therapies were superior to placebo in inducing remission of active CD and UC, and in preventing relapse of quiescent CD.

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Revisión sistemática

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Comparative efficacy of biologic therapy in biologic-naïve patients with Crohn disease: a systematic review and network meta-analysis.

Año 2014
Revista Mayo Clinic proceedings
Enlaces DOI , Pubmed

Este artículo incluye 52 Estudios primarios 53 Estudios primarios (52 referencias)

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OBJECTIVE:

To study the comparative efficacy of biologic therapy in the management of biologic-naïve patients with Crohn disease (CD).

PATIENTS AND METHODS:

We conducted a systematic review of randomized controlled trials published from January 1, 1985, through September 30, 2013, comparing biologic agents (infliximab [IFX], adalimumab [ADA], certolizumab pegol, natalizumab, vedolizumab, and ustekinumab) with each other or placebo for inducing and maintaining clinical remission in adults with moderate to severe CD. To increase comparability across trials, we focused on a subset of biologic-naïve patients for the induction end point and on responders to induction therapy for the maintenance end point. We followed a Bayesian network meta-analysis approach.

RESULTS:

We identified 17 randomized controlled trials of good methodological quality comparing 6 biologic agents with placebo, with no direct comparison of biologic agents. In network meta-analysis, we observed that IFX (relative risk [RR], 6.11; 95% credible interval [CrI], 2.49-18.29) and ADA (RR, 2.98; 95% CrI, 1.12-8.18), but not certolizumab pegol (RR, 1.48; 95% CrI, 0.76-2.93), natalizumab (RR, 1.36; 95% CrI, 0.69-2.86), vedolizumab (RR, 1.40; 95% CrI, 0.63-3.28), and ustekinumab (RR, 0.61; 95% CrI, 0.15-2.49), were more likely to induce remission than placebo. Similar results were observed for maintenance of remission. Infliximab had the highest probability of being ranked as the most efficacious agent for induction (86%) and ADA for maintenance of remission (48%).

CONCLUSION:

On the basis of network meta-analysis, IFX may be most efficacious agent for inducing remission in CD in biologic-naïve patients. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.

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Drug Class Review: Targeted Immune Modulators: Final Report Update 2

Año 2009
Libro Drug Class Reviews
Enlaces Pubmed

Este artículo incluye 216 Estudios primarios Estudios primarios (216 referencias) 25 Revisiones sistemáticas Revisiones sistemáticas (25 referencias)

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Targeted immune modulators, commonly referred to as biological response modifiers or simply biologics, are a relatively new category of medications used in the treatment of certain types of immunologic and inflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn’s disease, and ulcerative colitis. The US Food and Drug Administration approved the first of the biologics (infliximab) in 1998 and approved 9 additional agents since that time for treating various rheumatic conditions and plaque psoriasis: etanercept (1998), anakinra (2001), adalimumab (2002), alefacept (2003), efalizumab (2003), abatacept (2005), rituximab (2006), natalizumab (2008), and certolizumab pegol (2008). In this report, we review the comparative effectiveness, safety, and tolerability of targeted immune modulators.

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Revisión sistemática

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Biologic therapies in inflammatory bowel disease.

Año 2014
Autores Cohen LB , Nanau RM , Delzor F , Neuman MG
Revista Translational research : the journal of laboratory and clinical medicine
Enlaces DOI , Pubmed

Este artículo incluye 93 Estudios primarios 92 Estudios primarios (93 referencias)

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Inflammatory bowel disease, including its 2 entities ulcerative colitis and Crohn's disease, is a chronic medical condition characterized by the destructive inflammation of the intestinal tract. Biologics represent a class of therapeutics with immune intervention potential. These agents block the proinflammatory cascade that triggers the activation and proliferation of T lymphocytes at the level of the intestine, therefore reestablishing the balance between the pro- and anti-inflammatory messages. All 7 biologics showing clinical benefits in inflammatory bowel disease are monoclonal antibodies. The following systematic review discusses the pharmacokinetics and efficacy of the tumor necrosis factor blockers infliximab, adalimumab, certolizumab pegol, and golimumab. In addition, we describe the [alpha]4 integrin inhibitors natalizumab and vedolizumab, which are directed against cell adhesion molecules, as well as the interleukin 12/23 blocker ustekinumab.

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