Anakinra for Rheumatoid Arthritis

Mertens M, Singh JA

Published Online:

January 21, 2009

This summary of a Cochrane review presents what we know from research about the effect of Anakrina on rheumatoid arthritis (RA).

The review shows that in people with RA,

Taking Anakrina for 6 months may improve RA symptoms such as pain, function, and stiffness.

What are RA and Anakrina?

When you have rheumatoid arthritis, your immune system, which normally fights infection, attacks the lining of your joints. This makes your joints swollen, stiff and painful. The small joints of your hands and feet are usually affected first. There is no cure for RA at present, so the treatments aim to relieve pain and stiffness and improve your ability to move.

Anakinra is an interleukin-1 receptor antagonist which is a drug that blocks the inflammatory protein interleukin-1. The drug is used to slow the progression of moderate to severe active RA in patients over age 18 who have not responded to one or more of the disease-modifying anti-rheumatic drugs (DMARD). Anakrina can be used with other RA drugs.

Best estimate of what happens to people with RA who take Anakrina:

23 out of 100 people experienced improvement of RA symptoms such as pain, function, and stiffness when taking a placebo

38 out of 100 people experienced improvement of RA symptoms such as pain, function, and stiffness when taking Anakrina

15 more people out of 100 experienced improvement of RA symptoms after taking Anakrina for 6 months compared with taking a placebo.

Abstract (click to read)

Background:

In the past decade, a novel class of therapies directed against specific cytokines implicated in the disease process of rheumatoid arthritis (RA), called the 'Biologics' have greatly improved and expanded treatment for RA. Anakinra is an interleukin-1 receptor antagonist that is currently FDA-approved for moderate-severe RA that has been unresponsive to initial disease-modifying anti-rheumatic drugs (DMARD) therapy.

Objectives:

To evaluate the clinical effectiveness and safety of anakinra in adult patients with rheumatoid arthritis.

Search strategy:

We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), MEDLINE (1950 to Week 4 2008) , EMBASE (1980 to Week 5 2008), CINAHL (1982 to November 2007) and reference lists of articles.

Selection criteria:

Randomized controlled trials comparing anakinra alone or in combination with DMARDs or biologics to placebo or other DMARDs or biologics in patients >18 years old with rheumatoid arthritis.

Data collection and analysis:

Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.

Main results:

Five trials involving 2876 patients, 781 randomized to placebo and 2065 to anakinra, were included. There was a significant improvement in number of participants achieving ACR20 (38% versus 23%) who were treated with anakinra 50 to 150 mg daily versus placebo after 24 weeks. This 15% increase in patients achieving ACR20 with anakinra versus placebo is felt to be a clinically meaningful, though modest, outcome. Other efficacy data - including ACR50 (18% versus 7%), ACR70 (7% versus 2%), HAQ, visual analog score (VAS), Larsen radiographic scores, and change in erythrocyte sedimentation rate (ESR) - all demonstrated significant improvement with anakinra 50 to 150 mg daily versus placebo as well. There were no statistically significant differences noted in most safety outcomes with treatment with anakinra versus placebo - including number of withdrawals, deaths, adverse events (total and serious), and infections (total and serious). Injection site reactions were significantly increased, occurring in 1235/1729 (71%) versus 204/729 (28%) of patients treated with anakinra versus placebo, respectively. The incidence of serious infections was clinically higher, but not statistically different, in the anakinra (25/1366 patients, 1.8%) versus placebo group (3/534 patients, 0.6%).

Authors' conclusions:

Anakinra is a relatively safe and modestly efficacious biologic therapy for rheumatoid arthritis. Although head to head comparison trials have not been carried out, the amount of improvement is notably less when compared to studies using other biologic therapies. More studies are needed to evaluate safety and efficacy, especially in comparison to other therapies, and adverse event data for the long-term use of Anakinra has yet to be assessed.

This record should be cited as:

Mertens M, Singh JA. Anakinra for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD005121. DOI: 10.1002/14651858.CD005121.pub3

Assessed as up to date:

February 6, 2008

Find the research

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Primary Review Group:

Musculoskeletal Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

How effective is anakinra in adults with rheumatoid arthritis (RA)?

Bottom line:

Compared to placebo, adults with arthritis taking 50-150mg anakinra daily for 6 months had a 15% improvement in symptoms such as pain, function and stiffness (NNT* 8). Other efficacy data, including American College of Rheumatology (ACR) 50, ACR 70, Health Assessment Questionnaire (HAQ) score, Visual Analogue Scales, Larsen radiographic scores, and change in erythrocyte sedimentation rate, also demonstrated significant improvement with anakinra. When compared to other Cochrane Reviews of biologic therapies for RA, specifically etanercept, infliximab and adalimumab, the absolute benefit of treatment versus placebo for the proportion achieving ACR 20, ACR 50 and ACR 70 was noticeably lower. *NNT = number needed to treat to benefit 1 individual.

Caveat:

There was significant variability among the included studies with the specific outcomes measured, limiting the power of the systematic review. The method of randomisation was not reported in any study, and a number did not report full blinding. Only 1 study described a true intention-to-treat analysis.

Context:

RA is the most common inflammatory arthritis in adults, affecting 0.5 to 1% of the population worldwide. Anakinra is an interleukin-1 receptor antagonist that is currently Federal Drug Authority-approved for moderate to severe RA that has been unresponsive to initial disease-modifying anti-rheumatic drug (DMARD) therapy. The primary efficacy outcome measure in the trials was the ACR 20 - a 20% improvement in tender and swollen joint counts, and the same level of improvement in 3 of the following 5 variables: patient/physician global assessments, pain scores, HAQ, score and laboratory acute phase reactants.

Cochrane Systematic Review:

Mertens M and Singh JA. Anakinra for rheumatoid arthritis. Cochrane Reviews 2009, Issue 1. Article No. CD005121. DOI: 10.1002/14651858.CD005121.pub.3. This review contains 5 trials involving 2876 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Arthritis topics:

Rheumatoid Arthritis > Biologics

Health topics:

Rheumatology > Rheumatoid arthritis > Biologics

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Independent high-quality evidence for health care decision making

Anakinra for Rheumatoid Arthritis

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