Biologics for rheumatoid arthritis: an overview of Cochrane reviews

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Biologics for rheumatoid arthritis an overview
of Cochrane reviews

• Clinical

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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.
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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.

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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

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PICO(S) to assess eligible Cochrane Reviews

• Participants Adults (age 18 years)
• Intervention Biologic DMARDs given in standard,
  approved doses or biologic DMARDs plus other
  biologic/traditional DMARDs
• Comparison Placebo or placebo
  biologic/traditional DMARDs
• Outcomes 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)
• Studies 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

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Description of eligible studies

• 6 Cochrane Reviews of individual biologic DMARDs
  
• Abatacept (includes 7 RCTs)
• Adalimumab (includes 8 RCTs)
• Anakinra (includes 5 RCTs)
• Etanercept (includes 4 RCTs)
• Infliximab (includes 4 RCTs)
• Rituximab (includes 3 RCTs)
• Participant characteristics and outcome measures
  were similar across the Cochrane Reviews

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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
• Biologic DMARDs have similar effects
• But there are exceptions etanercept, rituximab,
  and adalimumab are all superior to anakinra

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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

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Results
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Summary of findings table ACR50
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.
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Summary of findings table ACR50
This is the effect of the biologic agent in
absolute terms
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.
Cochrane Journal Club
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Summary of findings table ACR50
This is the pooled effect of the comparator agent
in absolute terms
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.
Cochrane Journal Club
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Summary of findings table ACR50
This is the relative effect of the biologic agent
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.
Cochrane Journal Club
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Summary of findings table ACR50
This is the GRADE score of evidence quality for
this outcome
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.
Cochrane Journal Club
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Biologic DMARD vs other biologic DMARD The
ratio of risk ratios (RR) are displayed
graphically. A ratio of RRs lt 1 favours the drug
in the column on the right
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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)