Rapid and durable efficacy

Patients felt less pain and moved better over the long term1-3

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.

ACR20 response rates through Week 521-3*†

Graph of ACR20 response rates through week 52.
Graph of ACR20 response rates through week 52.

Some patients experienced ACR20 response as early as 1 to 2 weeks after starting CIMZIA1,3

*The same patients may not have responded at each time point.
†ITT-NRI: intent-to-treat nonresponder imputation.
‡ACR50 and ACR70 were prespecified secondary end points at Weeks 24 and 52.2

CIMZIA inhibited progression of structural damage1,2

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.

MTX inadequate responder mean change in mTSS at Week 521,2§

Graph of MTX inadequate responder mean change in mTSS at week 52.
Graph of MTX inadequate responder mean change in mTSS at week 52.

69% of patients had no radiographic progression2

X-Ray Image of the joint space narrowing and X-Ray Image of bone erosions.
X-Ray Image of the joint space narrowing and X-Ray Image of bone erosions.

§ITT-Lin Ext: intent-to-treat linear extrapolation.

Study design

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.

ACR, American College of Rheumatology; ACR20, American College of Rheumatology criteria for 20% response; ACR50, American College of Rheumatology criteria for 50% response; ACR70, American College of Rheumatology criteria for 70% response; mTSS, modified Total Sharp Score; MTX, methotrexate; QW, once a week; Q2W, every 2 weeks; RA, rheumatoid arthritis.

Efficacy in monotherapy

CIMZIA improved signs and symptoms in patients who cannot take MTX

Patients in the FAST4WARD study did not receive a loading dose of CIMZIA 400 mg at Weeks 0, 2, and 4.1,4

ACR20/50/70 responses at Week 244*

Graph of ACR20/50/70 responses at week 24.
Graph of ACR20/50/70 responses at week 24.

*mITT-NRI: modified intent-to-treat nonresponder imputation.

Study design

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; ACR20, American College of Rheumatology criteria for 20% response; ACR50, American College of Rheumatology criteria for 50% response; ACR70, American College of Rheumatology criteria for 70% response; DMARD, disease-modifying antirheumatic drug; MTX, methotrexate; Q4W, every 4 weeks; RA, rheumatoid arthritis.

Efficacy regardless of biologic experience

Consistent results regardless of prior TNFi exposure5

ACR20 responses in the overall and prior anti-TNF populations at Week 125*

Graph of ACR20 responses in overall and prior anti-TNF populations at week 12.
Graph of ACR20 responses in overall and prior anti-TNF populations at week 12.

*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

Study design

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

  • 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

DAS28(ESR) sustained remission and LDA6||

Graph of DAS28(ESR) sustained remission and LDA.
Graph of DAS28(ESR) sustained remission and LDA.

||FAS-NRI: full analysis set nonresponder imputation. 
Remission and LDA were sustained for at least 12 weeks (assessments were at Weeks 40 and 52).

Study design

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; ESR, erythrocyte sedimentation rate; 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; TNF, tumor necrosis factor; TNFi, tumor necrosis factor inhibitor.

Impact on patient

Reduction in tender and swollen joints through Week 521-3*†

Joint count based on:

  • 68 tender joint count evaluation
  • 66 swollen joint count evaluation

Mean reduction from baseline in tender and swollen joints through Week 521-3*†

Graph of ACR20 response rates through week 52.
Graph of ACR20 response rates through week 52.

CIMZIA decreased the number of swollen joints by approximately two-thirds and decreased the number of tender joints by more than half1,3

*ITT-LOCF: intent-to-treat last observation carried forward. 
†End points not adjusted for multiplicity. Nominal P value.

Study design

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.

Significant improvement in physical function was seen through 1 year in CIMZIA patients1-3

  • 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
     

Mean improvement from baseline in physical function—RA HAQ-DI improvement through Week 521-3‡

Graph of mean improvement from baseline in physical function - RA HAQ-DI improvement through week 52.
Graph of mean improvement from baseline in physical function - RA HAQ-DI improvement through week 52.
Boxed iconography of 8 meaningful measures for patients related to HAQ-DI. Icons include a person holding a dress, an alarm clock, a plate with a fork and spoon, a person walking, a person raising their hand, a hand gripping a ruler, hands being washed under a faucet, and a calendar with a clock.
Boxed iconography of 8 meaningful measures for patients related to HAQ-DI. Icons include a person holding a dress, an alarm clock, a plate with a fork and spoon, a person walking, a person raising their hand, a hand gripping a ruler, hands being washed under a faucet, and a calendar with a clock.

‡FAS-LOCF: full analysis set last observation carried forward. 
 

ACR, American College of Rheumatology; HAQ-DI, Health Assessment Questionnaire Disability Index; MCID, minimal clinically important difference; mTSS, modified Total Sharp Score; MTX-IR, methotrexate inadequate responders; QW, once a week; Q2W, every 2 weeks; RA, rheumatoid arthritis.

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IMPORTANT SAFETY INFORMATION & INDICATIONS

Serious and sometimes fatal side effects have been reported with CIMZIA, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens (such as Legionella or Listeria). Patients should be closely monitored for the signs and symptoms of infection during and after treatment with CIMZIA. Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member. CIMZIA is not indicated for use in pediatric patients.

INDICATIONS

CIMZIA is indicated for:

  • Reducing signs and symptoms of Crohn’s disease (CD) and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy
  • Treatment of adults with moderately to severely active rheumatoid arthritis (RA)
  • Treatment of adult patients with active psoriatic arthritis (PsA)
  • Treatment of adults with active ankylosing spondylitis (AS)
  • Treatment of adults with moderate-to-severe plaque psoriasis (PSO) who are candidates for systemic therapy or phototherapy
  • Treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation

IMPORTANT SAFETY INFORMATION (CONT)

CONTRAINDICATIONS

CIMZIA is contraindicated in patients with a history of hypersensitivity reaction to certolizumab pegol or to any of the excipients. Reactions have included angioedema, anaphylaxis, serum sickness, and urticaria.

SERIOUS INFECTIONS

Patients treated with CIMZIA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Discontinue CIMZIA if a patient develops a serious infection or sepsis.

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before CIMZIA use and during therapy. Initiate treatment for latent TB prior to CIMZIA use.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

Carefully consider the risks and benefits of treatment with CIMZIA prior to initiating therapy in the following patients: with chronic or recurrent infection; who have been exposed to TB; with a history of opportunistic infection; who resided in or traveled in regions where mycoses are endemic; with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with CIMZIA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

  • Do not start CIMZIA during an active infection, including localized infections.
  • Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection.
  • If an infection develops, monitor carefully and initiate appropriate therapy.

MALIGNANCY

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member. CIMZIA is not indicated for use in pediatric patients.

  • Consider the risks and benefits of CIMZIA treatment prior to initiating or continuing therapy in a patient with known malignancy.
  • In clinical trials, more cases of malignancies were observed among CIMZIA-treated patients compared to control patients.
  • In CIMZIA clinical trials, there was an approximately 2-fold higher rate of lymphoma than expected in the general U.S. population. Patients with rheumatoid arthritis, particularly those with highly active disease, are at a higher risk of lymphoma than the general population.
  • Malignancies, some fatal, have been reported among children, adolescents, and young adults being treated with TNF blockers. Approximately half of the cases were lymphoma, while the rest were other types of malignancies, including rare types associated with immunosuppression and malignancies not usually seen in this patient population.
  • Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including CIMZIA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn’s disease or ulcerative colitis, and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treating with CIMZIA in these patient types.
  • Cases of acute and chronic leukemia were reported with TNF blocker use.

HEART FAILURE

  • Worsening and new onset congestive heart failure (CHF) have been reported with TNF blockers. Exercise caution and monitor carefully.

HYPERSENSITIVITY

  • Angioedema, anaphylaxis, dyspnea, hypotension, rash, serum sickness, and urticaria have been reported following CIMZIA administration. If a serious allergic reaction occurs, stop CIMZIA and institute appropriate therapy. The needle shield inside the removable cap of the CIMZIA prefilled syringe contains a derivative of natural rubber latex which may cause an allergic reaction in individuals sensitive to latex.

HEPATITIS B VIRUS REACTIVATION

  • Use of TNF blockers, including CIMZIA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal.
  • Test patients for HBV infection before initiating treatment with CIMZIA.
  • Exercise caution in patients who are carriers of HBV and monitor them before and during CIMZIA treatment.
  • Discontinue CIMZIA and begin antiviral therapy in patients who develop HBV reactivation. Exercise caution when resuming CIMZIA after HBV treatment.

NEUROLOGIC REACTIONS

  • TNF blockers, including CIMZIA, have been associated with rare cases of new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, seizure disorder, optic neuritis, peripheral neuropathy, and Guillain-Barré syndrome.

HEMATOLOGIC REACTIONS

  • Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia has been infrequently reported with CIMZIA.
  • Consider stopping CIMZIA if significant hematologic abnormalities occur.

DRUG INTERACTIONS

  • Do not use CIMZIA in combination with other biological DMARDs.

AUTOIMMUNITY

  • Treatment with CIMZIA may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.

IMMUNIZATIONS

  • Patients on CIMZIA should not receive live or live-attenuated vaccines.

ADVERSE REACTIONS

  • The most common adverse reactions in CIMZIA clinical trials (≥8%) were upper respiratory infections (18%), rash (9%), and urinary tract infections (8%).

 

Please refer to full Prescribing Information.

US-CZ-2400178