biologics for rheumatoid arthritis

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Biologics for rheumatoid arthritis: an overview of Cochrane reviews

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Biologics for rheumatoid arthritis: an overview of Cochrane reviews:

Biologics for rheumatoid arthritis: an overview of Cochrane reviews Clinical

Clinical question:

Clinical question Do biologic disease-modifying anti-rheumatic drugs (DMARDs) help relieve symptoms of rheumatoid arthritis and reduce disease progression? Source: Singh JA, Christensen R, Wells GA, Suarez-Almazor ME, Buchbinder R, Lopez-Olivo MA, Tanjong Ghogomu E, Tugwell P. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD007848. DOI: 10.1002/14651858.CD007848.pub2. Cochrane Journal Club

Context:

Context Rheumatoid arthritis affects up to 1 in 100 people It causes considerable discomfort and limits quality of life, and can lead to severe joint destruction Biologic DMARDs inhibit tumour necrosis factor or other cytokines or cells that contribute to joint inflammation and destruction in RA. Cochrane Journal Club

Methods:

Methods A Cochrane ‘Overview of reviews’ Authors searched for eligible studies in The Cochrane Library , up to May 2009 Data extracted from included Cochrane Reviews used: Summary statistics calculated for vs placebo comparisons Indirect comparison methods used for head-to-head comparisons of the biologic DMARDs Cochrane Journal Club

‘PICO(S)’ to assess eligible Cochrane Reviews:

‘ PICO(S) ’ to assess eligible Cochrane Reviews P articipants: Adults (age ≥ 18 years ) I ntervention: Biologic DMARDs given in standard, approved doses; or biologic DMARDs plus other biologic/traditional DMARDs C omparison: Placebo; or placebo + biologic/traditional DMARDs O utcomes include: ACR50 (50% improvement in both tender and swollen joint counts and 50% improvement in at least 3 of 5 other assessments) Withdrawals due to adverse events (proxy measure of safety) S tudies: Cochrane Reviews (up-to-date and either in press or published) of randomized controlled trials (RCTs) of biologic DMARDs that: contain at least 1 RCT include clinically relevant outcomes have clear inclusion and exclusion criteria Cochrane Journal Club

Description of eligible studies:

Description of eligible studies 6 Cochrane Reviews of individual biologic DMARDs: Abatacept (includes 7 RCTs) Adalimumab (includes 8 RCTs) A nakinra (includes 5 RCTs) E tanercept (includes 4 RCTs) I nfliximab (includes 4 RCTs) R ituximab (includes 3 RCTs) Participant characteristics and outcome measures were similar across the Cochrane Reviews Cochrane Journal Club

Results: ACR50:

Results: ACR50 27 RCTs, including 20 that used concomitant methotrexate Biologic DMARDs vs placebo : Combined, any biologic DMARD more effective than placebo Individually , the biologic DMARDs are 2 to 3 times more effective than placebo (except for anakinra) Number-needed-to-treat-to-benefit (NNTB) ranged from 3 to 5 for most biologic DMARDs Biologic DMARD vs other biologic DMARD: B iologic DMARDs have similar effects B ut there are exceptions – etanercept , rituximab , and adalimumab are all superior to anakinra Cochrane Journal Club

Results: Withdrawals due to adverse events:

Results: Withdrawals due to adverse events 29 RCTs, including 21 that used concomitant therapy (generally methotrexate, another DMARD) Biologic DMARDs vs placebo : Higher risk of withdrawals with adalimumab , anakinra , and infliximab Similar risk of withdrawals with abatacept , etanercept , and rituximab Biologic DMARD vs other biologic DMARD: More withdrawals with adalimumab , anakinra , and infliximab than with etanercept Cochrane Journal Club

Results:

Cochrane Journal Club Results

Summary of findings table: ACR50:

Summary of findings table: ACR50 Biologic Control group risk Biologic risk Relative Risk Participants & studies Quality of evidence NNT (95% CI) Abatacept 207 per 1000 474 per 1000 2.29 (1.62 to 3.24) 1712 (6 studies) ⊕⊕⊕⊝ Moderate 4 (3 to 8) Adalimumab 207 per 1000 631 per 1000 3.05 (2.29 to 4.07) 2269 (8 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 4) Anakinra 207 per 1000 271 per 1000 1.31 (0.81 to 2.12) 815 (3 studies) ⊕⊕⊕⊝ Moderate Etanercept 207 per 1000 607 per 1000 2.93 (1.94 to 4.44) 1205 (4 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 6) Infliximab 207 per 1000 447 per 1000 2.16 (1.36 to 3.41) 819 (3 studies) ⊕⊕⊕⊕ High 5 (3 to 14) Rituximab 207 per 1000 604 per 1000 2.92 (1.76 to 4.83) 823 (3 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 7) Cochrane Journal Club Biologic DMARD vs placebo: This table shows the effect of the biologic DMARDs in relative and absolute terms. Each result is presented with the quality of the evidence as assessed using GRADE.

Summary of findings table: ACR50:

Summary of findings table: ACR50 Biologic Control group risk Biologic risk Relative Risk Participants & studies Quality of evidence NNT (95% CI) Abatacept 207 per 1000 474 per 1000 2.29 (1.62 to 3.24) 1712 (6 studies) ⊕⊕⊕⊝ Moderate 4 (3 to 8) Adalimumab 207 per 1000 631 per 1000 3.05 (2.29 to 4.07) 2269 (8 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 4) Anakinra 207 per 1000 271 per 1000 1.31 (0.81 to 2.12) 815 (3 studies) ⊕⊕⊕⊝ Moderate Etanercept 207 per 1000 607 per 1000 2.93 (1.94 to 4.44) 1205 (4 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 6) Infliximab 207 per 1000 447 per 1000 2.16 (1.36 to 3.41) 819 (3 studies) ⊕⊕⊕⊕ High 5 (3 to 14) Rituximab 207 per 1000 604 per 1000 2.92 (1.76 to 4.83) 823 (3 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 7) Cochrane Journal Club Biologic DMARD vs placebo: This table shows the effect of the biologic DMARDs in relative and absolute terms. Each result is presented with the quality of the evidence as assessed using GRADE. This is the effect of the biologic agent in absolute terms

Summary of findings table: ACR50:

Summary of findings table: ACR50 Biologic Control group risk Biologic risk Relative Risk Participants & studies Quality of evidence NNT (95% CI) Abatacept 207 per 1000 474 per 1000 2.29 (1.62 to 3.24) 1712 (6 studies) ⊕⊕⊕⊝ Moderate 4 (3 to 8) Adalimumab 207 per 1000 631 per 1000 3.05 (2.29 to 4.07) 2269 (8 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 4) Anakinra 207 per 1000 271 per 1000 1.31 (0.81 to 2.12) 815 (3 studies) ⊕⊕⊕⊝ Moderate Etanercept 207 per 1000 607 per 1000 2.93 (1.94 to 4.44) 1205 (4 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 6) Infliximab 207 per 1000 447 per 1000 2.16 (1.36 to 3.41) 819 (3 studies) ⊕⊕⊕⊕ High 5 (3 to 14) Rituximab 207 per 1000 604 per 1000 2.92 (1.76 to 4.83) 823 (3 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 7) Cochrane Journal Club Biologic DMARD vs placebo: This table shows the effect of the biologic DMARDs in relative and absolute terms. Each result is presented with the quality of the evidence as assessed using GRADE. This is the pooled effect of the comparator agent in absolute terms

Summary of findings table: ACR50:

Summary of findings table: ACR50 Biologic Control group risk Biologic risk Relative Risk Participants & studies Quality of evidence NNT (95% CI) Abatacept 207 per 1000 474 per 1000 2.29 (1.62 to 3.24) 1712 (6 studies) ⊕⊕⊕⊝ Moderate 4 (3 to 8) Adalimumab 207 per 1000 631 per 1000 3.05 (2.29 to 4.07) 2269 (8 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 4) Anakinra 207 per 1000 271 per 1000 1.31 (0.81 to 2.12) 815 (3 studies) ⊕⊕⊕⊝ Moderate Etanercept 207 per 1000 607 per 1000 2.93 (1.94 to 4.44) 1205 (4 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 6) Infliximab 207 per 1000 447 per 1000 2.16 (1.36 to 3.41) 819 (3 studies) ⊕⊕⊕⊕ High 5 (3 to 14) Rituximab 207 per 1000 604 per 1000 2.92 (1.76 to 4.83) 823 (3 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 7) Cochrane Journal Club Biologic DMARD vs placebo: This table shows the effect of the biologic DMARDs in relative and absolute terms. Each result is presented with the quality of the evidence as assessed using GRADE. This is the relative effect of the biologic agent

Summary of findings table: ACR50:

Summary of findings table: ACR50 Biologic Control group risk Biologic risk Relative Risk Participants & studies Quality of evidence NNT (95% CI) Abatacept 207 per 1000 474 per 1000 2.29 (1.62 to 3.24) 1712 (6 studies) ⊕⊕⊕⊝ Moderate 4 (3 to 8) Adalimumab 207 per 1000 631 per 1000 3.05 (2.29 to 4.07) 2269 (8 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 4) Anakinra 207 per 1000 271 per 1000 1.31 (0.81 to 2.12) 815 (3 studies) ⊕⊕⊕⊝ Moderate Etanercept 207 per 1000 607 per 1000 2.93 (1.94 to 4.44) 1205 (4 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 6) Infliximab 207 per 1000 447 per 1000 2.16 (1.36 to 3.41) 819 (3 studies) ⊕⊕⊕⊕ High 5 (3 to 14) Rituximab 207 per 1000 604 per 1000 2.92 (1.76 to 4.83) 823 (3 studies) ⊕⊕⊕⊝ Moderate 3 (2 to 7) Cochrane Journal Club Biologic DMARD vs placebo: This table shows the effect of the biologic DMARDs in relative and absolute terms. Each result is presented with the quality of the evidence as assessed using GRADE. This is the GRADE score of evidence quality for this outcome

Slide 15:

Biologic DMARD vs other biologic DMARD: The ratio of risk ratios (RR) are displayed graphically. A ratio of RRs < 1 favours the drug in the column on the right Cochrane Journal Club

Slide 16:

Cochrane Journal Club Useful links Cochrane Journal Club discussion points Biologics for rheumatoid arthritis: an overview of Cochrane reviews Cochrane Handbook for Systematic Reviews of Interventions: “ Indirect comparisons ” (section 16.6) “ Overviews of reviews ” (section 22)