Patients felt less pain and moved better over the long-term1-3
ACR20 response rates through
Week 521-3*† ACR20 response rates through Week 521-3*†
SOME EXPERIENCED ACR20 RESPONSE AS EARLY AS 1 TO 2 WEEKS AFTER STARTING CIMZIA1,3
Secondary efficacy variables
- ACR50 at Week 24: 37% CIMZIA + MTX vs. 8% placebo + MTX; P<0.0011-3‡
- ACR70 at Week 24: 21% CIMZIA + MTX vs. 3% placebo + MTX; P<0.0011-3‡
ACR response criteria assess changes in swollen and tender joints, pain, functional ability, patient and physician global assessment, and acute-phase reactant.
*The same patients may not have responded at each time point.
†ITT-NRI: intent-to-treat nonresponder imputation.
‡ACR50 and 70 were prespecified secondary end points at Weeks 24 and 52.2
RAPID 12
RAPID 1 was a 52-week, multicenter, randomized, double-blind, placebo-controlled study in 982 adult patients with active RA for at least 6 months prior to baseline, diagnosed according to ACR criteria, and with ≥9 swollen and tender joints. Patients were randomized to receive CIMZIA 200 mg (n=393), CIMZIA 400 mg (n=390), or placebo (n=199) subcutaneously Q2W following a loading dose of CIMZIA 400 mg or placebo at Weeks 0, 2, and 4. Patients in all 3 study arms also received MTX QW. The co-primary end points were ACR 20% improvement (ACR20) response rate at Week 24 and mean change from baseline in mTSS at Week 52.
CIMZIA inhibited progression of structural damage1,2
MTX inadequate responder mean change in mTSS at Week 521,2§
69% OF PATIENTS HAD NO RADIOGRAPHIC PROGRESSION2
Percentage of patients receiving CIMZIA + MTX who experienced no radiographic progression at 1 year vs. 52% of patients receiving placebo + MTX (no radiographic progression defined as mTSS ≤0).2
Mean baseline duration of disease was 6.1 years.
§ITT-Lin Ext: intent-to-treat linear extrapolation.
ACR, American College of Rheumatology; mTSS, modified Total Sharp Score; MTX, methotrexate; QW, once a week; Q2W, every 2 weeks; RA, rheumatoid arthritis.
CIMZIA improved signs and symptoms for patients who cannot take MTX
ACR20/50/70 responses at Week 244*
Patients in the FAST4WARD study did not receive a loading dose of CIMZIA 400 mg at Weeks 0, 2, and 4.1,4
*mITT-NRI: modified intent-to-treat nonresponder imputation.
FAST4WARD4
FAST4WARD was a double-blind, placebo-controlled, randomized, multicenter, 24-week clinical trial to study the safety and efficacy of CIMZIA 400 mg Q4W as monotherapy in adult patients with active RA who had failed at least 1 prior DMARD. Patients enrolled in this trial were aged 18 to 75 years with adult-onset active RA and were randomized to receive a lyophilized formulation of subcutaneous CIMZIA 400 mg (n=111) or placebo (sorbitol; n=109) at baseline and Q4W. In FAST4WARD, 82% of randomized patients had prior exposure to MTX, and patients were allowed to receive concurrent oral corticosteroids (prednisone equivalent ≤10 mg/day, stable for at least 4 weeks prior to enrollment and during the study); other corticosteroids were prohibited. The primary end point was ACR20 response rate at Week 24; secondary end points included ACR50/70 responses, ACR component scores, patient-reported outcomes (including physical function, health-related quality of life, pain, and fatigue), and safety.
ACR, American College of Rheumatology; DMARD, disease-modifying antirheumatic drug; MTX, methotrexate; Q4W, every 4 weeks; RA, rheumatoid arthritis.
Consistent results regardless of prior TNFi exposure5
ACR20 responses in the overall and prior anti-TNF populations at Week 125*
*ITT-NRI: intent-to-treat nonresponder imputation.
†±DMARD(s).
‡All CIMZIA patients received a loading dose of 400 mg at Weeks 0, 2, and 4.
§Patients were stratified at baseline by prior anti-TNF use (n=400 of 1063). Patients could have discontinued their prior anti-TNF for lack of efficacy, intolerance, or other reasons.5
REALISTIC5
The REALISTIC trial was a Phase 3b trial conducted to investigate the efficacy and safety of CIMZIA in a broad population of patients with active RA (including at least 5 tender and at least 4 swollen joints) and inadequate response to DMARDs. In this 12-week, double-blind period of the Phase 3b trial, patients with inadequate response to at least 1 DMARD were randomized 4:1 to CIMZIA (400 mg at Weeks 0, 2, and 4, followed by 200 mg Q2W) or placebo (Q2W), plus current therapy. Patients were stratified by prior anti-TNF use, disease duration (<2 years vs. ≥2 years), and concomitant use of MTX (yes/no). Patients (n=400 of 1063 or 37.6%) could have been treated with up to 2 anti-TNFs and could have discontinued their prior anti-TNF for lack of efficacy, intolerance, or other reasons. The primary end point was ACR20 response rate at Week 12.
Sustained remission through 1 year in DMARD-naïve patients6
DAS28(ESR) sustained remission and LDA6||
- C-EARLY was not powered to specifically evaluate remission or LDA at Week 52; however, these data suggest a directional similarity with the primary and key secondary end points
||FAS-NRI: full analysis set nonresponder imputation.
¶Remission and LDA were sustained for at least 12 weeks (assessments were at Weeks 40 and 52).
C-EARLY3,6
C-EARLY was a 24-month, randomized, double-blind, parallel-group, placebo-controlled, Phase 3 study consisting of 2 consecutive periods of 52 weeks each; period 1=Weeks 0 to 52, and period 2=Weeks 52 to 104. Subjects were randomly assigned at baseline (Week 0) to 1 of 2 treatment groups in a ratio of 3:1 to CIMZIA 400 mg at Weeks 0, 2, and 4 + MTX followed by CIMZIA 200 mg Q2W + MTX or placebo (2 syringes) at Weeks 0, 2, and 4 + MTX followed by placebo (1 syringe) Q2W + MTX. All patients received a loading dose of CIMZIA 400 mg or placebo at Weeks 0, 2, and 4. Those subjects randomized to the CIMZIA + MTX arm in period 1 and who were in sustained LDA (defined as DAS28[ESR] ≤3.2 at Weeks 40 and 52) at Week 52 were re-randomized to 1 of 3 treatment groups in a ratio of 2:3:2 (standard maintenance dose of CIMZIA 200 mg Q2W + MTX, reduced frequency dosing of CIMZIA 200 mg Q4W + MTX, and placebo + MTX) for period 2. Eligible patients must have had a diagnosis of adult-onset RA for <1 year as defined by the 2010 ACR/EULAR classification criteria at the screening visit. Patients were DMARD-naïve at screening and baseline, had a positive RF or positive ACPA result at screening, and had active RA disease as defined by ≥4 swollen joints and ≥4 tender joints (DAS28 joint) at screening and baseline, DAS28(ESR) >3.2 at screening and baseline, and CRP ≥10 mg/L at screening and/or ESR ≥28 mm/hour at screening and baseline.
ACPA, anti-citrullinated protein antibodies; ACR, American College of Rheumatology; CRP, C-reactive protein; DAS28(ESR), disease activity score, 28 joints (erythrocyte sedimentation rate); DMARD, disease-modifying antirheumatic drug; EULAR, European League Against Rheumatism; LDA, low disease activity; MTX, methotrexate; QW, once a week; Q2W, every 2 weeks; Q4W, every 4 weeks; RA, rheumatoid arthritis; RF, rheumatoid factor; TNFi, tumor necrosis factor inhibitor.
Reduction in tender and swollen joints through Week 521,3*†
CIMZIA DECREASED THE NUMBER OF SWOLLEN JOINTS BY APPROXIMATELY TWO-THIRDS AND DECREASED THE NUMBER OF TENDER JOINTS BY MORE THAN HALF1,3
Joint count based on:
- 68 tender joint count evaluation
- 66 swollen joint count evaluation
*ITT-LOCF: intent-to-treat last observation carried forward.
†End points not adjusted for multiplicity. Nominal P value.
RAPID 12
RAPID 1 was a 52-week, multicenter, randomized, double-blind, placebo-controlled study in 982 adult patients with active RA for at least 6 months prior to baseline, diagnosed according to ACR criteria, and with ≥9 swollen and tender joints. Patients were randomized to receive CIMZIA 200 mg (n=393), CIMZIA 400 mg (n=390), or placebo (n=199) subcutaneously Q2W following a load dose of CIMZIA 400 mg or placebo at Weeks 0, 2, and 4. Patients in all 3 study arms also received MTX QW. The co-primary end points were ACR 20% improvement (ACR20) response rate at Week 24 and mean change from baseline in mTSS at Week 52.
Significant improvement in physical function was seen through 1 year in CIMZIA
patients1-3 Significant improvement in physical function was seen through 1 year in CIMZIA patients1-3
Mean improvement from baseline in physical function—RA HAQ-DI improvement through Week 521-3‡
8 meaningful measures for patients: HAQ-DI7
- HAQ-DI scores range from 0=best to 3=worst
- Baseline HAQ-DI score was 1.75 for CIMZIA and placebo1
- Change from baseline in HAQ-DI scores represents improvements in patients’ ability to perform the following: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity. Physical function was a prespecified secondary end point1-3
- MCID was defined as a reduction in HAQ-DI from baseline of ≥0.222
‡FAS-LOCF: full analysis set last observation carried forward.
ACR, American College of Rheumatology; HAQ-DI, Health Assessment Questionnaire Disability Index; MCID, minimum clinically important difference; mTSS, modified Total Sharp Score; MTX-IR, methotrexate inadequate responders; QW, once a week; Q2W, every 2 weeks; RA, rheumatoid arthritis.
Safety profile for RA in the RAPID-1 study1,3
General overview of TEAEs (safety population)1,3
*Events assigned a "possible," "probable," or "definite" causality assessment by the Investigator.
TEAEs reported by ≥3% of patients through Week 521
MTX, methotrexate; Q2W, every 2 weeks; RA, rheumatoid arthritis; TEAE, treatment-emergent adverse event.