Neue Studien

Certolizumab pegol – drei neue Studien

Three studies of Certolizumab pegol

Certolizumab pegol plus Methotrexate is significantly more effective than placebo plus Methotrexate in active rheumatoid arthritis
Kexstone E et al. Arthritis Rheum Vol. 58, 2008: 3319-3329

Summary
52 week, phase 3, multicentre, randomized, double-blind, placebo-controlled study including 982 patients. Subcutaneous Certolizumab pegol was given at 400 mg at weeks 0, 2, and 4, and continued in subsequent dosages of 200 or 400 mg every 2 weeks plus Methotrexate, while the control group received placebo plus Methotrexate. End points were ACR20 and a mean change in modified total Sharp score at week 52.

At week 24, ACR20 response rates for Certolizumab pegol were about 60% in both treatment groups as compared with 13.6% for the placebo group. The differences in ACR20 response rates were significant at week 1 and sustained to week 52. The radiographic progression from baseline was significantly reduced in the Certolizumab groups at week 52 (0.4 units for the 200 mg group, 0.2 unit for the 400 mg group) as compared with placebo treated patients (2.8 units). Side effects were mild and moderate; the overall incidents of infectious adverse events were similar in all 3 treatment groups, while severe infections led to 6 drop-outs in each of the Certolizumab groups, while there was none in the placebo group.

Efficacy and safety of Certolizumab pegol plus Methotrexate in active rheumatoid arthritis: the RAPID 2 study
Smolen JS et al. Ann Rheum Dis published online 17 Nov 2008; doi:10.1136/ard.2008.101659

Summary
International, multicenter, phase 3, randomized, double-blind, placebo-controlled study comparing Certolizumab groups (plus MTX) to a group receiving placebo plus MTX.

This 24 week study shows that Certolizumab achieved in both dosage groups (200 and 400 mg every 2 weeks) a higher ACR20 response compared to placebo (around 57% in each Certolizumab group versus 8.7% in the placebo group). Within this time frame of 24 weeks the inhibition of radiographic progression was significantly better in the Certolizumab groups compared to placebo. While overall side effects were mild, serious infections were found in 3.2 and 2.4% of the Certolizumab groups compared to none in the placebo group. 5 patients developed tuberculosis (Certolizumab groups).

Efficacy and safety of Certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study
Fleischmann R et al. Ann Rheum Dis published online 17 Nov 2008; doi: 10.1136/ard 2008.099291

Summary
24 week, multicenter, randomized, double-blind, placebo-controlled study involving 220 patients previously failing > 1 DMARD. Monotherapy with either subcutaneous Certolizumab pegol 400 mg or placebo every 4 weeks.

At week 24 the ACR20 response rates were 45.5% for Certolizumab pegol 400 mg versus 9.3% for placebo. The differences were statistically significant already from week 1 through week 24. Side effects were comparable within the groups; serious infections were found in 1.8% in the Certolizumab group compared to 0 in the placebo group.

Overall conclusion
Certolizumab is a novel TNF-alpha-inhibitor (PEGylated, Fc-free). The results of the 3 published studies indicate that it compares to the well-known characteristics of the now available TNF-blockers in terms of clinical efficacy and inhibition of radiographic progression. The results comparing continued treatment with 2 weekly 400 mg versus 200 mg of Certolizumab do not show major differences. As with other TNF-blockers, infections appeared to be the main concern.

Overall, this novel TNF-inhibitor shows a fast onset of action and compares well to the available TNF-blockers. It remains to be seen, whether combination with Methotrexate is superior to Certolizumab alone, and which dosage regimen will be best in treating RA-patients.

Beat A. Michel

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