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Twenty-eight-week results from the REALISTIC phase IIIb randomized trial: efficacy, safety and predictability of response to certolizumab pegol in a diverse rheumatoid arthritis population.

Weinblatt ME, Fleischmann R, van Vollenhoven RF, Emery P, Huizinga TW, Cutolo M, van der Heijde D, Duncan B, Davies O, Luijtens K, Dougados M - Arthritis Res. Ther. (2015)

Bottom Line: Adverse event rates were similar for placebo → CZP and CZP → CZP patients, with no new safety signals identified.Failure to achieve improvements in DAS28(ESR), SJC or CDAI within the first 12 weeks of CZP therapy was associated with a low chance of achieving LDA at week 28.No new safety signals were observed.

View Article: PubMed Central - PubMed

Affiliation: Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. mweinblatt@partners.org.

ABSTRACT

Introduction: This 28-week, phase IIIb study assessed safety and maintenance of response to certolizumab pegol (CZP) in a diverse population of rheumatoid arthritis (RA) patients, stratified by prior anti-TNF exposure, concomitant methotrexate (MTX) use and disease duration. The ability to predict achievement of low disease activity (LDA) at week 28 from improvements in Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), swollen joint count (SJC) and Clinical Disease Activity Index (CDAI) up to week 12 was assessed.

Methods: The 28-week study population included all patients who completed the double-blind (DB) phase and entered the open-label (OL) phase, receiving 200 mg CZP every 2 weeks (Q2W) ≥16 weeks. In the 12-week DB period, patients with active RA and an inadequate response to ≥1 disease-modifying antirheumatic drug (DMARD) were randomized 4:1 to CZP (400 mg at weeks 0, 2 and 4 then 200 mg Q2W) or placebo (Q2W), stratified by prior anti-TNF use, concomitant use of MTX and disease duration (<2 years vs. ≥2 years).

Results: A total of 955 patients entered the OL phase. At week 28, similar clinical improvements were seen in those receiving CZP throughout (CZP → CZP; n = 771) and those receiving placebo during the DB phase and switching to CZP in the OL phase (placebo → CZP; n = 184) (ACR20 response rate = 59.7 % vs. 53.3 %; ACR50/ACR70 response rates were also similar). Effect of CZP treatment was similar regardless of prior anti-TNF use, disease duration and concomitant DMARDs, based on ACR20 response rates. The percentage of patients achieving DAS28(ESR) LDA at week 28 was calculated for DAS28(ESR), SJC or CDAI responders at earlier time points. Reductions from baseline (Δ) of DAS28(ESR) <1.2, ΔSJC <25 % or ΔCDAI <10 by week 12 were associated with <9 % chance of achieving LDA at week 28 regardless of prior anti-TNF exposure. Adverse event rates were similar for placebo → CZP and CZP → CZP patients, with no new safety signals identified.

Conclusions: A diverse population of RA patients with varying disease duration showed rapid and sustained clinical improvements on CZP treatment, regardless of prior anti-TNF or concomitant DMARD use. Failure to achieve improvements in DAS28(ESR), SJC or CDAI within the first 12 weeks of CZP therapy was associated with a low chance of achieving LDA at week 28. No new safety signals were observed.

Trial registration: ClinicalTrials.gov, NCT00717236 , 15 July 2008.

No MeSH data available.


Related in: MedlinePlus

a REALISTIC trial design. b Subject disposition. aDB phase. bOne week 12 CZP completer discontinued after week 12 due to an AE, did not receive any study medication in the OL phase, and was not included in the OL analysis set. AE adverse event, CZP certolizumab pegol, DMARD disease-modifying antirheumatic drug, OLE open-label extension, Q2W every other week
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Fig1: a REALISTIC trial design. b Subject disposition. aDB phase. bOne week 12 CZP completer discontinued after week 12 due to an AE, did not receive any study medication in the OL phase, and was not included in the OL analysis set. AE adverse event, CZP certolizumab pegol, DMARD disease-modifying antirheumatic drug, OLE open-label extension, Q2W every other week

Mentions: During the initial 12-week period patients were randomized 4:1 by means of an interactive voice response system to either 400 mg CZP at weeks 0, 2 and 4 followed by 200 mg CZP every 2 weeks (Q2W) (CZP patient group), or placebo (0.9 % saline) Q2W (placebo group), stratified by prior anti-TNF use, concomitant use of MTX and disease duration (<2 years vs. ≥2 years) to ensure balanced treatment assignments [6]. Patients who had completed 12 weeks of treatment with either 200 mg CZP Q2W or placebo were eligible to receive OL CZP 200 mg Q2W for ≥16 weeks (Fig. 1a). Results from the 16-week OL phase are reported here, together with the association between DAS28(ESR) low disease activity at week 28 and failure to achieve early responses.Fig. 1


Twenty-eight-week results from the REALISTIC phase IIIb randomized trial: efficacy, safety and predictability of response to certolizumab pegol in a diverse rheumatoid arthritis population.

Weinblatt ME, Fleischmann R, van Vollenhoven RF, Emery P, Huizinga TW, Cutolo M, van der Heijde D, Duncan B, Davies O, Luijtens K, Dougados M - Arthritis Res. Ther. (2015)

a REALISTIC trial design. b Subject disposition. aDB phase. bOne week 12 CZP completer discontinued after week 12 due to an AE, did not receive any study medication in the OL phase, and was not included in the OL analysis set. AE adverse event, CZP certolizumab pegol, DMARD disease-modifying antirheumatic drug, OLE open-label extension, Q2W every other week
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4644627&req=5

Fig1: a REALISTIC trial design. b Subject disposition. aDB phase. bOne week 12 CZP completer discontinued after week 12 due to an AE, did not receive any study medication in the OL phase, and was not included in the OL analysis set. AE adverse event, CZP certolizumab pegol, DMARD disease-modifying antirheumatic drug, OLE open-label extension, Q2W every other week
Mentions: During the initial 12-week period patients were randomized 4:1 by means of an interactive voice response system to either 400 mg CZP at weeks 0, 2 and 4 followed by 200 mg CZP every 2 weeks (Q2W) (CZP patient group), or placebo (0.9 % saline) Q2W (placebo group), stratified by prior anti-TNF use, concomitant use of MTX and disease duration (<2 years vs. ≥2 years) to ensure balanced treatment assignments [6]. Patients who had completed 12 weeks of treatment with either 200 mg CZP Q2W or placebo were eligible to receive OL CZP 200 mg Q2W for ≥16 weeks (Fig. 1a). Results from the 16-week OL phase are reported here, together with the association between DAS28(ESR) low disease activity at week 28 and failure to achieve early responses.Fig. 1

Bottom Line: Adverse event rates were similar for placebo → CZP and CZP → CZP patients, with no new safety signals identified.Failure to achieve improvements in DAS28(ESR), SJC or CDAI within the first 12 weeks of CZP therapy was associated with a low chance of achieving LDA at week 28.No new safety signals were observed.

View Article: PubMed Central - PubMed

Affiliation: Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. mweinblatt@partners.org.

ABSTRACT

Introduction: This 28-week, phase IIIb study assessed safety and maintenance of response to certolizumab pegol (CZP) in a diverse population of rheumatoid arthritis (RA) patients, stratified by prior anti-TNF exposure, concomitant methotrexate (MTX) use and disease duration. The ability to predict achievement of low disease activity (LDA) at week 28 from improvements in Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), swollen joint count (SJC) and Clinical Disease Activity Index (CDAI) up to week 12 was assessed.

Methods: The 28-week study population included all patients who completed the double-blind (DB) phase and entered the open-label (OL) phase, receiving 200 mg CZP every 2 weeks (Q2W) ≥16 weeks. In the 12-week DB period, patients with active RA and an inadequate response to ≥1 disease-modifying antirheumatic drug (DMARD) were randomized 4:1 to CZP (400 mg at weeks 0, 2 and 4 then 200 mg Q2W) or placebo (Q2W), stratified by prior anti-TNF use, concomitant use of MTX and disease duration (<2 years vs. ≥2 years).

Results: A total of 955 patients entered the OL phase. At week 28, similar clinical improvements were seen in those receiving CZP throughout (CZP → CZP; n = 771) and those receiving placebo during the DB phase and switching to CZP in the OL phase (placebo → CZP; n = 184) (ACR20 response rate = 59.7 % vs. 53.3 %; ACR50/ACR70 response rates were also similar). Effect of CZP treatment was similar regardless of prior anti-TNF use, disease duration and concomitant DMARDs, based on ACR20 response rates. The percentage of patients achieving DAS28(ESR) LDA at week 28 was calculated for DAS28(ESR), SJC or CDAI responders at earlier time points. Reductions from baseline (Δ) of DAS28(ESR) <1.2, ΔSJC <25 % or ΔCDAI <10 by week 12 were associated with <9 % chance of achieving LDA at week 28 regardless of prior anti-TNF exposure. Adverse event rates were similar for placebo → CZP and CZP → CZP patients, with no new safety signals identified.

Conclusions: A diverse population of RA patients with varying disease duration showed rapid and sustained clinical improvements on CZP treatment, regardless of prior anti-TNF or concomitant DMARD use. Failure to achieve improvements in DAS28(ESR), SJC or CDAI within the first 12 weeks of CZP therapy was associated with a low chance of achieving LDA at week 28. No new safety signals were observed.

Trial registration: ClinicalTrials.gov, NCT00717236 , 15 July 2008.

No MeSH data available.


Related in: MedlinePlus