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Comparing Biologics for Rheumatoid Arthritis Treatment



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Am Fam Physician. 2010 Jul 15;82(2):196.

Background: Biologic agents may help patients with rheumatoid arthritis (RA) who have an unsatisfactory response to traditional disease-modifying antirheumatic drugs (DMARDs) such as methotrexate. However, there are few studies comparing the relative effectiveness and safety of biologics against each other. Singh and colleagues compared the benefits and safety of these agents in patients with RA.

The Study: The authors performed a meta-analysis of all Cochrane reviews of biologic therapy for RA. The data were then used to calculate the relative benefits and safety of the agents compared with each other. Benefit was defined as a 50 percent improvement in symptoms of RA using the American College of Rheumatology criteria (ACR50), and safety was defined as the number of withdrawals from therapy because of adverse events.

Results: A total of six Cochrane reviews comprising 31 studies were evaluated. Most of the trials compared a biologic with placebo; both groups also received a traditional DMARD such as methotrexate. Overall, biologics were more likely than placebo to achieve an ACR50 response (odds ratio [OR] = 3.35), but were also more likely than placebo to be stopped because of adverse events (OR = 1.39). Each biologic was more likely than placebo to achieve an ACR50 (OR = 2.92 to 4.97) except for anakinra (Kineret). Patients taking adalimumab, anakinra, and infliximab were more likely than those taking placebo to discontinue treatment (OR = 1.54 to 2.21), but no difference was noted in those taking abatacept, etanercept, or rituximab (Rituxan; see accompanying table).

Table.

Comparison of Biologic Agents vs. Placebo in the Treatment of Rheumatoid Arthritis

Biologic agent Likelihood of achieving ACR50 Safety*
Odds ratio NNT Odds ratio NNH

Abatacept (Orencia)

2.98

5

NS

NS

Adalimumab (Humira)

3.70

4

1.54

39

Anakinra (Kineret)

NS

NS

1.67

31

Etanercept (Enbrel)

4.97

3

NS

NS

Infliximab (Remicade)

2.92

5

2.21

18

Rituximab (Rituxan)

4.10

4

NS

NS


note: All biologic and placebo groups also received a traditional disease-modifying antirheumatic agent such as methotrexate.

*— Likelihood of withdrawal due to adverse effects.

ACR50 = 50 percent reduction in symptoms according to the American College of Rheumatology's criteria for rheumatoid arthritis; NNH = number needed to harm; NNT = number needed to treat; NS = not significant.

Table.   Comparison of Biologic Agents vs. Placebo in the Treatment of Rheumatoid Arthritis

View Table

Table.

Comparison of Biologic Agents vs. Placebo in the Treatment of Rheumatoid Arthritis

Biologic agent Likelihood of achieving ACR50 Safety*
Odds ratio NNT Odds ratio NNH

Abatacept (Orencia)

2.98

5

NS

NS

Adalimumab (Humira)

3.70

4

1.54

39

Anakinra (Kineret)

NS

NS

1.67

31

Etanercept (Enbrel)

4.97

3

NS

NS

Infliximab (Remicade)

2.92

5

2.21

18

Rituximab (Rituxan)

4.10

4

NS

NS


note: All biologic and placebo groups also received a traditional disease-modifying antirheumatic agent such as methotrexate.

*— Likelihood of withdrawal due to adverse effects.

ACR50 = 50 percent reduction in symptoms according to the American College of Rheumatology's criteria for rheumatoid arthritis; NNH = number needed to harm; NNT = number needed to treat; NS = not significant.

Indirect comparison of the treatments showed that anakinra was less effective than adalimumab and etanercept in achieving ACR50. Fewer patients stopped etanercept because of adverse effects than did persons taking adalimumab, anakinra, or infliximab. The treatments were similarly effective in patients regardless of duration of RA.

Conclusion: Etanercept and adalimumab are more effective than anakinra in improving the symptoms of RA, and etanercept is better tolerated than adalimumab, anakinra, and infliximab. This may help physicians make evidence-based choices about using pharma-cotherapies in the treatment of RA.

Source

Singh JA, et al. A network meta-analysis of randomized controlled trials of biologics for rheumatoid arthritis: a Cochrane overview. CMAJ. November 24, 2009;181(11):787–796.



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