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Efficacy of biological agents administered as monotherapy in rheumatoid arthritis: a Bayesian mixed-treatment comparison analysis.

Migliore A, Bizzi E, Egan CG, Bernardi M, Petrella L - Ther Clin Risk Manag (2015)

Bottom Line: Likewise, for ACR50 and ACR70 outcome responses, tocilizumab had a 99.8% or 98.7% probability of being the best treatment, respectively, compared to other treatments or placebo.Tocilizumab increased the relative probability of being the best treatment (vs methotrexate) by 3.2-fold (odds ratio: 2.1-3.89) for all ACR outcomes.Tocilizumab offered the greatest possibility of obtaining an ACR20, ACR50, and ACR70 outcome vs other monotherapies or placebo.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology Unit, San Pietro Fatebenefratelli Hospital, Rome, Italy.

ABSTRACT

Background: Biological agents provide an important therapeutic alternative for rheumatoid arthritis patients refractory to conventional disease-modifying antirheumatic drugs. Few head-to-head comparative trials are available.

Purpose: The aim of this meta-analysis was to compare the relative efficacy of different biologic agents indicated for use as monotherapy in rheumatoid arthritis.

Methods: A systemic literature search was performed on electronic databases to identify articles reporting double-blind randomized controlled trials investigating the efficacy of biologic agents indicated for monotherapy. Efficacy was assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria at 16-24 weeks. Relative efficacy was estimated using Bayesian mixed-treatment comparison models. Outcome measures were expressed as odds ratio and 95% credible intervals.

Results: Ten randomized controlled trials were selected for data extraction and analysis. Mixed-treatment comparison analysis revealed that tocilizumab offered 100% probability of being the best treatment for inducing an ACR20 response versus placebo, methotrexate, adalimumab, or etanercept. Likewise, for ACR50 and ACR70 outcome responses, tocilizumab had a 99.8% or 98.7% probability of being the best treatment, respectively, compared to other treatments or placebo. Tocilizumab increased the relative probability of being the best treatment (vs methotrexate) by 3.2-fold (odds ratio: 2.1-3.89) for all ACR outcomes.

Conclusion: Tocilizumab offered the greatest possibility of obtaining an ACR20, ACR50, and ACR70 outcome vs other monotherapies or placebo.

No MeSH data available.


Related in: MedlinePlus

Relative odds of different drug comparisons being the most effective treatment for obtaining improvement in ACR outcome.Notes: (A) ACR20, (B) ACR50, and (C) ACR70 outcomes. Data presented as odds ratio for different drug comparisons. Solid line denotes mean odds ratio for all treatment comparisons. Black dotted-line denotes an odds ratio of 1. For clarity, each figure is divided into three sections by treatment type vs methotrexate; biologic vs biologic; and vs placebo.Abbreviations: A, adalimumab; ACR, American College of Rheumatology; E, etanercept; M, methotrexate; P, placebo; T, tocilizumab.
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f2-tcrm-11-1325: Relative odds of different drug comparisons being the most effective treatment for obtaining improvement in ACR outcome.Notes: (A) ACR20, (B) ACR50, and (C) ACR70 outcomes. Data presented as odds ratio for different drug comparisons. Solid line denotes mean odds ratio for all treatment comparisons. Black dotted-line denotes an odds ratio of 1. For clarity, each figure is divided into three sections by treatment type vs methotrexate; biologic vs biologic; and vs placebo.Abbreviations: A, adalimumab; ACR, American College of Rheumatology; E, etanercept; M, methotrexate; P, placebo; T, tocilizumab.

Mentions: MTC analysis revealed that for ACR20, tocilizumab had a probability of 100% of being the best treatment in terms of producing an ACR20 response at 24 weeks compared with placebo, MTX, adalimumab, or etanercept (Table 4). This equated to a relative odds of being the best treatment of approximately 3-fold greater for tocilizumab compared to either MTX (OR =3.19, 95% CrI =2.46–4.09), etanercept (OR =3.89, 95% CrI =2.46–5.81), or adalimumab (OR =2.49, 95% CrI =1.61–3.71) (Table 4). As expected, placebo did not offer significant probability of attaining ACR20 response over other treatments (Figure 2A), and etanercept only offered marginal advantage compared to MTX. A similar benefit was also observed for ACR50 response, whereby tocilizumab had a 99.8% probability of being the best treatment compared to etanercept, which had a probability of 0.14%, and adalimumab, a probability of 0.02% (Table 5). The relative odds of being the best treatment was approximately 2.5-fold greater for tocilizumab compared to MTX (OR =3.1, 95% CrI =2.33–3.97), etanercept (OR =2.11, 95% CrI =1.27–3.31), or adalimumab (OR =2.25, 95% CrI =1.39–3.47) (Table 5). Interestingly, little difference was noted between adalimumab and etanercept, while both etanercept and adalimumab fared better than MTX (Figure 2B). With regard to ACR70, tocilizumab showed a probability of 98.7% of being the best treatment in inducing ACR70 remission compared to etanercept, which had a probability of 1.2%, and adalimumab, which had a probability of 0.12% (Table 6). The relative odds of being the best treatment in inducing ACR70 response was approximately 2.5-fold greater for tocilizumab compared to MTX (OR =3.56, 95% CrI =2.51–4.92), etanercept (OR =2.14, 95% CrI =1.11–3.74), or adalimumab (OR =2.27, 95% CrI =1.32–3.73) (Table 6). Similar to ACR50 outcome, both etanercept and adalimumab offered greater probability of attaining ACR70 response compared to MTX (Figure 2C). For all ACR outcomes, tocilizumab increased the relative probability of being the best treatment by approximately 3-fold (OR =2.1–3.89) compared to other treatments, (data not shown).


Efficacy of biological agents administered as monotherapy in rheumatoid arthritis: a Bayesian mixed-treatment comparison analysis.

Migliore A, Bizzi E, Egan CG, Bernardi M, Petrella L - Ther Clin Risk Manag (2015)

Relative odds of different drug comparisons being the most effective treatment for obtaining improvement in ACR outcome.Notes: (A) ACR20, (B) ACR50, and (C) ACR70 outcomes. Data presented as odds ratio for different drug comparisons. Solid line denotes mean odds ratio for all treatment comparisons. Black dotted-line denotes an odds ratio of 1. For clarity, each figure is divided into three sections by treatment type vs methotrexate; biologic vs biologic; and vs placebo.Abbreviations: A, adalimumab; ACR, American College of Rheumatology; E, etanercept; M, methotrexate; P, placebo; T, tocilizumab.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562742&req=5

f2-tcrm-11-1325: Relative odds of different drug comparisons being the most effective treatment for obtaining improvement in ACR outcome.Notes: (A) ACR20, (B) ACR50, and (C) ACR70 outcomes. Data presented as odds ratio for different drug comparisons. Solid line denotes mean odds ratio for all treatment comparisons. Black dotted-line denotes an odds ratio of 1. For clarity, each figure is divided into three sections by treatment type vs methotrexate; biologic vs biologic; and vs placebo.Abbreviations: A, adalimumab; ACR, American College of Rheumatology; E, etanercept; M, methotrexate; P, placebo; T, tocilizumab.
Mentions: MTC analysis revealed that for ACR20, tocilizumab had a probability of 100% of being the best treatment in terms of producing an ACR20 response at 24 weeks compared with placebo, MTX, adalimumab, or etanercept (Table 4). This equated to a relative odds of being the best treatment of approximately 3-fold greater for tocilizumab compared to either MTX (OR =3.19, 95% CrI =2.46–4.09), etanercept (OR =3.89, 95% CrI =2.46–5.81), or adalimumab (OR =2.49, 95% CrI =1.61–3.71) (Table 4). As expected, placebo did not offer significant probability of attaining ACR20 response over other treatments (Figure 2A), and etanercept only offered marginal advantage compared to MTX. A similar benefit was also observed for ACR50 response, whereby tocilizumab had a 99.8% probability of being the best treatment compared to etanercept, which had a probability of 0.14%, and adalimumab, a probability of 0.02% (Table 5). The relative odds of being the best treatment was approximately 2.5-fold greater for tocilizumab compared to MTX (OR =3.1, 95% CrI =2.33–3.97), etanercept (OR =2.11, 95% CrI =1.27–3.31), or adalimumab (OR =2.25, 95% CrI =1.39–3.47) (Table 5). Interestingly, little difference was noted between adalimumab and etanercept, while both etanercept and adalimumab fared better than MTX (Figure 2B). With regard to ACR70, tocilizumab showed a probability of 98.7% of being the best treatment in inducing ACR70 remission compared to etanercept, which had a probability of 1.2%, and adalimumab, which had a probability of 0.12% (Table 6). The relative odds of being the best treatment in inducing ACR70 response was approximately 2.5-fold greater for tocilizumab compared to MTX (OR =3.56, 95% CrI =2.51–4.92), etanercept (OR =2.14, 95% CrI =1.11–3.74), or adalimumab (OR =2.27, 95% CrI =1.32–3.73) (Table 6). Similar to ACR50 outcome, both etanercept and adalimumab offered greater probability of attaining ACR70 response compared to MTX (Figure 2C). For all ACR outcomes, tocilizumab increased the relative probability of being the best treatment by approximately 3-fold (OR =2.1–3.89) compared to other treatments, (data not shown).

Bottom Line: Likewise, for ACR50 and ACR70 outcome responses, tocilizumab had a 99.8% or 98.7% probability of being the best treatment, respectively, compared to other treatments or placebo.Tocilizumab increased the relative probability of being the best treatment (vs methotrexate) by 3.2-fold (odds ratio: 2.1-3.89) for all ACR outcomes.Tocilizumab offered the greatest possibility of obtaining an ACR20, ACR50, and ACR70 outcome vs other monotherapies or placebo.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology Unit, San Pietro Fatebenefratelli Hospital, Rome, Italy.

ABSTRACT

Background: Biological agents provide an important therapeutic alternative for rheumatoid arthritis patients refractory to conventional disease-modifying antirheumatic drugs. Few head-to-head comparative trials are available.

Purpose: The aim of this meta-analysis was to compare the relative efficacy of different biologic agents indicated for use as monotherapy in rheumatoid arthritis.

Methods: A systemic literature search was performed on electronic databases to identify articles reporting double-blind randomized controlled trials investigating the efficacy of biologic agents indicated for monotherapy. Efficacy was assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria at 16-24 weeks. Relative efficacy was estimated using Bayesian mixed-treatment comparison models. Outcome measures were expressed as odds ratio and 95% credible intervals.

Results: Ten randomized controlled trials were selected for data extraction and analysis. Mixed-treatment comparison analysis revealed that tocilizumab offered 100% probability of being the best treatment for inducing an ACR20 response versus placebo, methotrexate, adalimumab, or etanercept. Likewise, for ACR50 and ACR70 outcome responses, tocilizumab had a 99.8% or 98.7% probability of being the best treatment, respectively, compared to other treatments or placebo. Tocilizumab increased the relative probability of being the best treatment (vs methotrexate) by 3.2-fold (odds ratio: 2.1-3.89) for all ACR outcomes.

Conclusion: Tocilizumab offered the greatest possibility of obtaining an ACR20, ACR50, and ACR70 outcome vs other monotherapies or placebo.

No MeSH data available.


Related in: MedlinePlus