12 research outputs found
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Certolizumab pegol (CDP870) for rheumatoid arthritis in adults
Background
Tumour necrosis factor (TNF)-alpha inhibitors are beneficial for the treatment of rheumatoid arthritis (RA) for reducing the risk of joint damage, improving physical function and improving the quality of life. This review is an update of the 2014 Cochrane Review of the treatment of RA with certolizumab pegol.
Objectives
To assess the clinical benefits and harms of certolizumab pegol (CZP) in people with RA who have not responded well to conventional disease-modifying anti-rheumatic drugs (DMARDs).
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL: Cochrane Library 2016, Issue 9), MEDLINE, Embase, Web of Knowledge, reference lists of articles, clinicaltrials.gov and ICTRP of WHO. The searches were updated from 2014 (date of the last search for the previous version) to 26 September 2016.
Selection criteria
Randomised controlled trials that compared certolizumab pegol with any other agent, including placebo or methotrexate (MTX), in adults with active RA, regardless of current or prior treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as MTX.
Data collection and analysis
Two review authors independently checked search results, extracted data and assessed trial quality. We resolved disagreements by discussion or referral to a third review author.
Main results
We included 14 trials in this update, three more than previously. Twelve trials (5422 participants) included measures of benefit. We pooled 11 of them, two more than previously. Thirteen trials included information on harms, (5273 participants). 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. In Phase III trials, the comparator was placebo plus MTX in seven trials and placebo in five. In the two Phase II trials the comparator was only placebo.
The approved dose of certolizumab pegol, 200 mg every other week, produced clinically important improvements at 24 weeks for the following outcomes:
- American College of Rheumatology (ACR) 50% improvement (pain, function and other symptoms of RA): 25% absolute improvement (95% confidence interval (CI) 20% to 33%); number need to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 5); risk ratio (RR) 3.80 (95% CI 2.42 to 5.95), 1445 participants, 5 studies.
- The Health Assessment Questionnaire (HAQ): -12% absolute improvement (95% CI -9% to -14%); NNTB of 8 (95% CI 7 to 11); mean difference (MD) - 0.35 (95% CI -0.43 to -0.26; 1268 participants, 4 studies) (scale 0 to 3; lower scores mean better function).
- Proportion of participants achieving remission (Disease Activity Score (DAS) < 2.6) absolute improvement 10% (95% CI 8% to 16%); NNTB of 8 (95% CI 6 to 12); risk ratio (RR) 2.94 (95% CI 1.64 to 5.28), 2420 participants, six studies.
- Radiological changes: erosion score (ES) absolute improvement -0.29% (95% CI -0.42% to -0.17%); NNTB of 6 (95% CI 4 to 10); MD -0.67 (95% CI -0.96 to -0.38); 714 participants, two studies (scale 0 to 230), but not a clinically important difference.
-Serious adverse events (SAEs) were statistically but not clinically significantly more frequent for certolizumab pegol (200 mg every other week) with an absolute rate difference of 3% (95% CI 1% to 4%); number needed to treat for an additional harmful outcome (NNTH) of 33 (95% CI 25 to 100); Peto odds ratio (OR) 1.47 (95% CI 1.13 to 1.91); 3927 participants, nine studies.
There was a clinically significant increase in all withdrawals in the placebo groups (for all doses and at all follow-ups) with an absolute rate difference of -29% (95% CI -16% to -42%), NNTH of 3 (95% CI 2 to 6), RR 0.47 (95% CI 0.39 to 0.56); and there was a clinically significant increase in withdrawals due to adverse events in the certolizumab groups (for all doses and at all follow-ups) with an absolute rate difference of 2% (95% CI 0% to 3%); NNTH of 58 (95% CI 28 to 329); Peto OR 1.45 (95% CI 1.09 to 1.94) 5236 participants Twelve studies.
We judged the quality of evidence to be high for ACR50, DAS remission, SAEs and withdrawals due to adverse events, and moderate for HAQ and radiological changes, due to concerns about attrition bias. For all withdrawals we judged the quality of evidence to be moderate, due to inconsistency.
Authors' conclusions
The results and conclusions did not change from the previous review. There is a moderate to high certainty of evidence from randomised controlled trials that certolizumab pegol, alone or combined with methotrexate, is beneficial in the treatment of RA for improved ACR50 and health-related quality of life, an increased chance of remission of RA, and reduced joint damage as seen on x-ray. Fewer people stopped taking their treatment, but most of these who did stopped due to serious adverse events. Adverse events were more frequent with active treatment. We found a clinically but not statistically significant risk of serious adverse events
Survival of jak inhibitors: real-word data from the biobadaser III registry
Background JAK inhibitors (JAKi) have been recently authorized in the European Union. JAKi long-term performance in the clinical practice setting still needs to be assessed. Drug survival reflects a drug’s effectiveness, safety, and tolerability; thus, it is an important measurement for real-world studies.
Objectives To describe the pattern of use of JAKi in real-world dataset, and to analyze the drug survival as a group (tofacitinib+baricitinib).
Methods Information was obtained from BIOBADASER III, an ongoing observational longitudinal multicenter cohort of patients with rheumatic diseases treated with biologic or targeted synthetic (b/ts) DMARDs in Spain. All subjects with current or previous JAKi use were included and followed until September 2018. Clinical characteristics of the patients were analyzed. Drug survival (overall, and for biologic-naive and biologic-experienced patients) was determined using Kaplan-Meier analysis.
Results 149 patients, 75.2% women, were treated with JAKi, receiving a total of 152 cycles of treatment (50.7% tofacitinib, 49.3% baricitinib; 3 patients had both). The most frequent diagnosis was rheumatoid arthritis (RA, 92.6%), and there is a small number of off-label uses (6%), depicted at Table 1. Use on psoriatic arthritis is scarce (1.3%). Concomitant use of methotrexate (MTX) was registered in 68 patients (45.6%). Previous use of bDMARDs was high (n=124, 81.6%); drug survival rate for biologic-experienced patients was 81.7% and 78.7% at 6 and 12 months. None of the JAKi treatments in biologic-naive patients (n=18, 18.4%) were discontinued during follow-up. Pooled survival rate of JAKi was 85.0% and 82.5% at 6 and 12 months (Figure 1). Discontinuation was seen in 19 treatments (12.5%); the reasons were inefficacy (n=15, 9.9%) or adverse events (n=4, 2.6%).
Conclusion The current use of JAKi in Spain is mainly in RA and as 2nd line after bDMARDs. The use of JAKi in psoriatic arthritis is still scarce and a small group of patients are treated off-label. Less than half use combination therapy with MTX. Overall survival of JAKi is superior to 80% at 12 months. A longer follow-up is needed to continue analyzing the survival of JAKi in a real-world context