Certolizumab pegol for treating adults with rheumatoid arthritis

We conducted an updated review of the effect of certolizumab pegol for adults with RA. We searched all relevant studies until June 2014 and found 11 studies with 4324 people.

In people with rheumatoid arthritis:

- certolizumab pegol probably improved the American College of Rheumatology ACR50 (pain, function and other symptoms of RA), health-related quality of life, and the chance of remission of RA,

- certolizumab pegol probably reduced joint damage as seen on the x-ray,

- certolizumab pegol probably increased serious adverse events,

- with certolizumab pegol fewer people stopped taking their treatment, but most of these people stopped due to serious adverse events.

What is rheumatoid arthritis and what is certolizumab pegol?

When you have RA your immune system becomes overactive and attacks the lining of your joints. This makes your joints swollen, stiff and painful. There is no cure for RA at present, so the treatments aim is to relieve pain and stiffness and improve your ability to move.

Certolizumab pegol works by blocking a substance produced by the body known as tumour necrosis factor alpha (TNF). Certolizumab pegol is given by injections under the skin, either by patients themselves or someone else.

What happens to people with rheumatoid arthritis who take certolizumab pegol 200 mg every other week after six months?

ACR50 (a 50% improvement in the number of tender or swollen joints and other outcomes such as pain and disability):

- 27 more people out of 100 experienced improvement in the symptoms of their rheumatoid arthritis after six months with certolizumab pegol (absolute improvement 27%),

- 36 people out of 100 who took certolizumab pegol experienced improvement compared to 9 people out of 100 who took a placebo (a fake injection).

Health-related quality of life (Health Assessment Questionnaire):

- the additional benefit on this questionnaire for people who took certolizumab pegol was a change of -0.35 units on a scale 0 to 3 units (with 3 indicating a worse health state, therefore a negative change indicates improvement) (absolute improvement 12%),

- people on certolizumab pegol who completed the Health Assessment Questionnaire (HAQ) had a change of -0.48 points on a scale of 0 to 3 compared to a change of -0.13 points on a scale of 0 to 3 for people who took a placebo.

Remission (absence of clinical signs of inflammation):

- 11 more people out of 100 experienced remission with certolizumab pegol (absolute improvement 11%),

- 13 people out of 100 who took certolizumab pegol experienced remission compared to 2 people out of 100 who took a placebo.

Radiological changes (x-rays of the joints):

- the joint damage in people who took certolizumab pegol was 0.07 units less on a scale of 0 to 230 units (absolute improvement -0.29%),

- the damage to joints in people who took certolizumab pegol was 0.04 units less on a scale of 0 to 230 units compared to people who took a placebo whose joint damage was 0.7 units more on a scale of 0 to 230 units.

Serious adverse events:

- 4 more people out of 100 experienced serious adverse events with certolizumab pegol (4% absolute harm),

- 8 people out of 100 who took certolizumab pegol experienced serious adverse events compared to 4 people out of 100 who took a placebo.

What happens after 52 weeks to people with rheumatoid arthritis who take certolizumab pegol 200 mg and certolizumab 400 mg?

All withdrawals:

- 33 less people out of 100 stopped taking their treatment after 52 weeks with certolizumab pegol compared with placebo (absolute improvement 34%),

- 23 people out of 100 who took certolizumab pegol stopped taking their treatment compared to 56 people out of 100 who took placebo.

Withdrawals due to adverse events:

- 2 more people out of 100 stopped taking their treatment due to adverse events after 52 weeks with certolizumab pegol compared with placebo (absolute improvement 2%),

- 5 people out of 100 who took certolizumab pegol stopped taking their treatment due to adverse events compared to 3 people out of 100 who took placebo.

Authors' conclusions: 

The results and conclusions did not change from the previous review. There is moderate-level evidence from randomised controlled trials that certolizumab pegol alone or combined with methotrexate is beneficial in the treatment of RA. Adverse events were more frequent with active treatment. We found a potential risk of serious adverse events.

Read the full abstract...
Background: 

Tumour necrosis factor (TNF)-alpha inhibitors are beneficial for the treatment of rheumatoid arthritis (RA) in terms of reducing the risk of joint damage, improving physical function and improving quality of life. This Cochrane review is an update of a review of the treatment of RA with certolizumab pegol that was first published in 2011.

Objectives: 

To assess the clinical benefits and harms of certolizumab pegol (CDP870) in patients with RA who have not responded well to conventional disease-modifying anti-rheumatic drugs (DMARDs).

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 5), MEDLINE, EMBASE, Scopus, TOXLINE, Web of Knowledge; websites of the US Food and Drug Administration (FDA) and European Medicines Evaluation Agency (EMEA); reference lists of articles; and searched http/clinicaltrials.gov. The searches were updated from 2009 (date of last search for the original review) to 5 June 2014.

Selection criteria: 

Randomised controlled trials that compared certolizumab pegol with any other agent including placebo or methotrexate (MTX) in adult patients with active RA despite current or prior treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as MTX.

Data collection and analysis: 

Two authors independently assessed search results, trial quality and extracted data. Disagreements were resolved by discussion or referral to a third author.

Main results: 

Eleven trials were included in this update. Ten (4324 patients) were included in the pooled analysis for benefits, five more than previously, and 10 (3711 patients) in the pooled analysis for harms, four more trials (1930 patients) than previously. The duration of follow-up varied from 12 to 52 weeks and the range of doses of certolizumab pegol varied from 50 to 400 mg given subcutaneously (sc). In phase III trials, the control was placebo plus MTX in five trials and placebo in four trials. The risk of bias of the included studies was assessed as low but there may have been a risk of attrition bias.

Statistically significant improvements were observed at 24 weeks with the approved dose of 200 mg certolizumab pegol every other week, in 1) American College of Rheumatology (ACR) 50% improvement: 27% absolute improvement (95% CI 20% to 33%), NNT of 4 (95% CI 3 to 8), risk ratio (RR) 3.80 (95% CI 2.42 to 5.95); 2) the Health Assessment Questionnaire (HAQ): -12% absolute improvement (95% CI -9% to -14%), NNT of 6 (95% CI 5 to 8), mean difference (MD) - 0.35 (95% CI -0.43 to -0.26) (scale 0 to 3); 3) Disease Activity Score (DAS) remission improvement: absolute improvement 11% (95% CI 8% to 15%), NNT of 9 (95% CI 4 to 20), RR 8.47 (95% CI 4.15-17.28); and 4) radiological changes: erosion score (ES) absolute improvement -0.29% (95% CI -0.42% to -0.17%), NNT of 6 (95% CI 4 to 10), MD -0.67 (95% CI -0.96 to -0.38) (scale 0 to 230). Serious adverse events were statistically significantly more frequent for certolizumab pegol (200 mg every other week) with an absolute rate difference of 4% (95% CI 2% to 6%), NNTH of 32 (95% CI 17 to 88), Peto odds ratio (OR) 1.77 (95% CI 1.27 to 2.46). There was a statistically significant increase in all withdrawals in the placebo groups (for all doses and all follow-ups) with an absolute rate difference of -34% (95% CI -18% to -50%), NNTH of 4 (95% CI 3 to 5), NNTH of 4 (95% CI 3 to 5), RR 0.42 (95% CI 0.36 to 0.50); and there was a statistically significant increase in all withdrawals due to adverse events in the certolizumab groups (for all doses and all follow-up) with an absolute rate difference of 2% (95% CI 1% to 3%), NNTH of 55 (95% CI 27 to 238), Peto OR 1.66 (95% CI 1.15 to 2.37).

The risk of bias was low and the quality of evidence was downgraded to moderate because of high rates of dropouts (> 20%) in most of the trials. We did not find any problems with inconsistency, indirectness, imprecision or publication bias.

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