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In people with rheumatoid arthritis, ‘biologics’ + methotrexate improve symptoms more than either alone

Nam JL, Ramiro S, Gaujoux-Viala C, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2014;73:516-28.

Review question

In people with rheumatoid arthritis (RA), do biologic disease-modifying antirheumatic drugs (biologics) improve symptoms and slow disease progression?

Background

RA is a chronic (long-term) condition that results in inflammation, usually of the small joints in your hands and feet. It affects the lining of the joints, causing painful swelling that can eventually wear down bone. Unlike the more common osteoarthritis, which is due to wear and tear damage, RA is an autoimmune disease in which the body’s immune system attacks the joints.

Treatment of RA focuses on controlling symptoms (pain and swelling) and preventing joint damage. Doctors will usually start by prescribing drugs that have the fewest side-effects; if they don’t work well, they move onto different types of drugs or combinations of drugs. Biologics are a fairly new type of medication that is prescribed for people who do not respond to disease-modifying antirheumatic drugs (DMARDs) or who have had side-effects.

How the review was done

The researchers did a systematic review, including studies available up to February 2013.

They found 108 reports. Only the results of randomized controlled trials are reported here because they make up the strongest evidence available. The safety of biologics was not addressed in this report.

All studies included at least 50 people and lasted 6 months or more.

People had RA or were at risk of developing RA. Some people had previously been treated with DMARDs, such as methotrexate, but they did not work or did not work well enough. Others had not previously used DMARDs.

A variety of biologics were studied, including infliximab, etanercept, adalimumab, certolizumab pegol, golimumab, anakinra, rituximab, and tocilizumab.

What the researchers found

People with early RA who had not previously used methotrexate

Biologics plus methotrexate improved symptoms more than methotrexate alone.

People who had not previously used methotrexate

Biologics plus methotrexate improved symptoms more than methotrexate alone.

People who previously used methotrexate, but their symptoms did not improve as much as expected

Biologics plus methotrexate improved symptoms more than methotrexate alone.

Biologics plus methotrexate did not improve symptoms more than biologics alone.

People who did not respond to previous DMARDs

Biologics plus DMARDs improved symptoms more than DMARDs alone.

People who did not respond to previous methotrexate

Biologics plus methotrexate improved symptoms more than biologics alone.

Conclusion

In people with RA, biologics plus methotrexate or another DMARD improve symptoms more than biologics alone or methotrexate or other DMARDs alone.

Biologics vs control in people with rheumatoid arthritis

Group

Treatment and comparison

Number of trials (people)

Rate of events with treatment

Rate of events with control

Absolute effect of treatment*

People with early RA who had not previously used methotrexate

Biologics + methotrexate vs methotrexate alone

9 trials (5,253 people)

38%

23%

About 15 more people out of 100 improved

People who had not previously used methotrexate

Biologics + methotrexate vs biologics alone

3 trials (1,601 people)

34%

25%

About 9 more people out of 100 improved

People who did not respond well to previous methotrexate

Biologics + methotrexate vs methotrexate alone

24 trials (8,783 people)

17%

4%

About 13 more people out of 100 improved

 

Biologics + methotrexate vs biologics alone

5 trials (1,653 people)

14%

13%

No effect†

People who did not respond to any previous conventional DMARD

Biologics + DMARDs vs DMARDs alone

7 trials (3,130 people)

22%

6%

About 16 more people out of 100 improved

People who did not respond to previous methotrexate

Biologics + methotrexate vs biologics alone

4 trials (1,504 people)

43%

31%

About 12 more people out of 100 improved

*Outcome is improvement in tender or swollen joint counts and pain, disability, or signs measured by doctors.

†Although the rates for the 2 groups look a little different, the differences were not statistically significant—this means that the differences could simply be due to chance rather than due to the different treatments.

 




Glossary

Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.

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