REALISTIC Phase IIIb clinical trial, showed rapid and consistent improvements across a broad population of patients taking Cimzia® whether they had previously received TNF inhibitors or not
Cimzia® also associated with rapid improvements in fatigue, sleep problems and pain, as early as Week 2 of treatment
LONDON, UK & BRUSSELS, BELGIUM | May 26, 2011 | UCB today announced data which showed that the addition of Cimzia® (certolizumab pegol) to current therapy was associated with a rapid and consistent clinical response in a diverse group of rheumatoid arthritis (RA) patients.1 Consistent efficacy was observed across patients taking certolizumab pegol whether they had previously received TNF inhibitors or not and whether they received certolizumab pegol monotherapy[1] or with concomitant DMARDs.1 The results are from a subgroup[2] analysis of the REALISTIC (RA Evaluation in Subjects Receiving TNF Inhibitor Certolizumab Pegol) study, presented during the Annual Meeting of the European League Against Rheumatism (EULAR) in London, May 25-28.
“These results are encouraging because they demonstrate the clinical usefulness of certolizumab pegol in a broad population of patients with RA and reflect the patient variability we see day-to-day in clinical practice,” said Roy Fleischmann, MD, clinical professor in the Department of Internal Medicine at the University of Texas Southwestern Medical School.
In the overall study population, ACR20 response rates at Week 12 were statistically significantly higher in the certolizumab pegol group (51.1%) compared to placebo (25.9%). There was no significant difference in response rates among patients in the certolizumab pegol group who had previously been treated with TNF inhibitors (47.2%) and those who had not (53.5%), and similarly no significant difference among patients receiving certolizumab pegol monotherapy* (47.6%) compared to those receiving concomitant DMARDs (52.0%).1
Further analysis of the REALISTIC phase IIIb study revealed that the addition of certolizumab pegol to current therapy was associated with clinically meaningful reductions in fatigue and sleep problems, as well as improvements in pain and patient-assessed disease activity (PtGA) compared to the placebo group.2 Patient-reported outcomes such as fatigue, pain and sleep problems are common symptoms in RA.
At Week 12, significantly more patients in the certolizumab pegol group compared to the placebo group experienced improvements in fatigue (56.4% vs 46.2%, p<0.01), sleep problems (49.7% vs 42.5%, p=0.058), pain (59.0% vs 42.0%, p<0.001) and PtGA (59.5% vs 42.5%, p<0.001). Significant reductions in fatigue, pain and PtGA were recorded as early as Week 2 in the certolizumab pegol group.2
“These results demonstrate that the benefits of treatment with certolizumab pegol extend into areas that are meaningful for patients in terms of quality of life,” said Dr Janet Pope, Professor of the Department of Medicine, Division of Rheumatology and Epidemiology and Biostatistics at the University of Western Ontario, London, Ontario, Canada. “Factors such as fatigue, pain and sleep disturbance can have a significant impact on day-to-day life, so making a positive difference in these areas can be very significant for patients.”
Treatment with certolizumab pegol was generally well tolerated in the REALISTIC phase IIIb study population and subgroup analyses. Adverse and serious adverse event rates were comparable between certolizumab pegol and placebo treatment groups with no new safety signals observed through Week 12 and were not significantly different among patients with and without prior TNF inhibitor use. The most common adverse events were upper respiratory or urinary tract infections. The most common serious adverse events were infections and infestations. Of these, the most common serious infections were lower respiratory tract and lung infections.3
[1] Cimzia can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
[2] The analyses done by prior/no prior TNF inhibitor use were pre-specified; analyses by number and type of prior TNF inhibitors, monotherapy and number and type of concomitant DMARDs were post hoc.1
About REALISTIC
REALISTIC (RA Evaluation in Subjects Receiving TNF Inhibitor Certolizumab Pegol) is a multicenter phase IIIb trial in patients with active rheumatoid arthritis who have shown inadequate response to disease-modifying antirheumatic drugs, including patients with/without prior TNF-inhibitor exposure, with/without concomitant methotrexate or other disease-modifying anti-rheumatic drugs (DMARDs); and varying lengths of disease duration. The study demonstrated that – in a diverse group of RA patients reflecting those seen in daily clinical practice (including those with prior TNF-inhibitor use) – addition of Cimzia® to current therapy was associated with a rapid clinical response consistent in all strata, improved function and reduced disease activity.
A sub-analysis investigated Cimzia® as monotherapy or concomitantly with DMARDs in subgroups of patients with or without prior TNF inhibitor use. Active RA patients with inadequate response to ≥1 DMARD were randomised 4:1 to Cimzia® 400mg at Weeks 0, 2 and 4 followed by 200mg every 2 weeks or placebo injection (control) every 2 weeks + current therapy. Primary outcome was ACR20 at Week 12. Randomisation was stratified by prior TNF inhibitor use, concomitant use of methotrexate (MTX), and disease duration (<2 y vs ≥2 y). Treatment effect differences between subgroups were assessed by interactions (treatment by covariate) at 10% significance level.
Another sub-analysis determined the impact of Cimzia® on fatigue, sleep problems and other patient reported outcomes (PROs) in the REALISTIC study. Active RA patients with inadequate response to ≥1 DMARD were randomised 4:1 to CZP 400mg (n=851) at Weeks 0, 2 and 4 followed by 200mg every 2 weeks or placebo injection (control, n=212) every 2 weeks added to current therapy. PROs included fatigue (Fatigue Assessment Scale [FAS; 0–10 numeric rating scale]), sleep quantity and quality (Sleep Problem Index II domain of the Medical Outcomes Study sleep scale [MOS-SPI]), pain (0–100mm visual analogue scale [VAS]), and patient’s global assessment of disease activity (PtGA, 0–100mm VAS). The minimal clinically important difference (MCID) is a clinically relevant change in a patient’s status. The percentage of patients reporting MCIDs was determined: ≥1 for FAS, ≥6 for MOS-SPI, and ≥10mm for pain-VAS and PtGA. Correlations between PROs and DAS28 were also assessed (Pearson correlations [rho], CZP group only).
Cimzia® (certolizumab pegol) in European Union/ EEA important safety information
Cimzia® was studied in 2367 patients with RA in controlled and open label trials for up to 57 months. The commonly reported adverse reactions (1-10%) in clinical trials with Cimzia® and post-marketing were viral infections (includes herpes, papillomavirus, influenza), bacterial infections (including abscess), rash, headache (including migraine), asthenia, leukopaenia (including lymphopaenia, neutropaenia), eosinophilic disorder, pain (any sites), pyrexia, sensory abnormalities, hypertension, pruritis (any sites), hepatitis (including hepatic enzyme increase), injection site reactions. Serious adverse reactions include sepsis, opportunistic infections, tuberculosis, herpes zoster, lymphoma, leukaemia, solid organ tumours, angioneurotic edema, cardiomyopathies (includes heart failure), ischemic coronary artery disorders, pancytopaenia, hypercoagulation (including thrombophlebitis, pulmonary embolism), cerebrovascular accident, vasculitis, hepatitis/hepatopathy (includes cirrhosis), and renal impairment/nephropathy (includes nephritis). In RA controlled clinical trials, 5% of patients discontinued taking Cimzia® due to adverse events vs. 2.5% for placebo.
Cimzia® is contraindicated in patients with hypersensitivity to the active substance or any of the excipients, active tuberculosis or other severe infections such as sepsis or opportunistic infections, moderate to severe heart failure.
Before initiation of Cimzia®, evaluate patients for both active or inactive (latent) tuberculosis infection. Monitor patients for the development of signs and symptoms of infection during and after treatment with Cimzia®. If an infection develops, monitor carefully, and stop Cimzia® if infection becomes serious.
TNF blockers including Cimzia® may increase the risk: of reactivation of Hepatitis B Virus (HBV) in patients who are chronic carriers of the virus; of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease; of formation of autoantibodies and uncommonly of the development of a lupus-like syndrome; of severe hypersensitivity reactions. If a patient develops any of these adverse reactions, Cimzia® should be discontinued and appropriate therapy instituted.
With the current knowledge, a possible risk for the development of lymphomas, leukaemia or other malignancies in patients treated with a TNF antagonist cannot be excluded. Rare cases of neurological disorders, including seizure disorder, neuritis and peripheral neuropathy, have been reported in patients treated with Cimzia®.
Adverse reactions of the hematologic system, including medically significant cytopenia, have been infrequently reported with Cimzia®. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on Cimzia®. Consider discontinuation of Cimzia® therapy in patients with confirmed significant haematological abnormalities.
The use of Cimzia® in combination with anakinra or abatacept is not recommended due to a potential increased risk of serious infections. As no data are available, Cimzia® should not be administered concurrently with live vaccines or attenuated vaccines. The 14-day half-life of Cimzia® should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on Cimzia® should be closely monitored for infections.
Please consult the full prescribing information in relation to other side effects, full safety and prescribing information. European SmPC date of revision February 2011.
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001037/WC500069763.pdf
About CIMZIA®
Cimzia® is the only PEGylated anti-TNF (Tumor Necrosis Factor). Cimzia® has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha. Over the past decade, TNF-alpha has emerged as a major target of basic research and clinical investigation. This cytokine plays a key role in mediating pathological inflammation, and excess TNF-alpha production has been directly implicated in a wide variety of diseases. The U.S. Food and Drug Administration (FDA) has approved Cimzia® for reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy and for the treatment of adults with moderately to severely active rheumatoid arthritis. Cimzia® in combination with MTX, is approved in the EU for the treatment of moderate to severe active RA in adult patients inadequately responsive to disease-modifying antirheumatic drugs (DMARDs) including MTX. Cimzia® can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. UCB is also developing Cimzia® in other autoimmune disease indications. Cimzia® is a registered trademark of UCB PHARMA S.A.
About UCB
UCB, Brussels, Belgium (www.ucb.com) is a biopharmaceutical company dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Employing more than 9000 people in over 40 countries, UCB produced revenue of EUR 3.1 billion in 2009. UCB is listed on Euronext Brussels (symbol: UCB).
References
1. Weinblatt M et al. Certolizumab pegol as monotherapy or with concomitant DMARDs in patients with active rheumatoid arthritis (RA) with or without prior TNF inhibitor use: analyses of the REALISTIC 12-week Phase IIIb randomised controlled study. FRI0214
2. Pope J et al. Rapid reductions in fatigue and sleep problems, and correlation with improvements in patient-reported outcomes in patients with active RA treated with certolizumab pegol in the REALISTIC 12-week Phase IIIb randomised controlled study. THU0240
3. Weinblatt M et al. Efficacy and Safety of Certolizumab Pegol in a Clinically Representative Population of Patients With Active Rheumatoid Arthritis: Results of the REALISTIC Phase IIIb Randomized Controlled Study. 2010 American College of Rheumatology annual meeting
SOURCE: UCB
Post Views: 78
REALISTIC Phase IIIb clinical trial, showed rapid and consistent improvements across a broad population of patients taking Cimzia® whether they had previously received TNF inhibitors or not
Cimzia® also associated with rapid improvements in fatigue, sleep problems and pain, as early as Week 2 of treatment
LONDON, UK & BRUSSELS, BELGIUM | May 26, 2011 | UCB today announced data which showed that the addition of Cimzia® (certolizumab pegol) to current therapy was associated with a rapid and consistent clinical response in a diverse group of rheumatoid arthritis (RA) patients.1 Consistent efficacy was observed across patients taking certolizumab pegol whether they had previously received TNF inhibitors or not and whether they received certolizumab pegol monotherapy[1] or with concomitant DMARDs.1 The results are from a subgroup[2] analysis of the REALISTIC (RA Evaluation in Subjects Receiving TNF Inhibitor Certolizumab Pegol) study, presented during the Annual Meeting of the European League Against Rheumatism (EULAR) in London, May 25-28.
“These results are encouraging because they demonstrate the clinical usefulness of certolizumab pegol in a broad population of patients with RA and reflect the patient variability we see day-to-day in clinical practice,” said Roy Fleischmann, MD, clinical professor in the Department of Internal Medicine at the University of Texas Southwestern Medical School.
In the overall study population, ACR20 response rates at Week 12 were statistically significantly higher in the certolizumab pegol group (51.1%) compared to placebo (25.9%). There was no significant difference in response rates among patients in the certolizumab pegol group who had previously been treated with TNF inhibitors (47.2%) and those who had not (53.5%), and similarly no significant difference among patients receiving certolizumab pegol monotherapy* (47.6%) compared to those receiving concomitant DMARDs (52.0%).1
Further analysis of the REALISTIC phase IIIb study revealed that the addition of certolizumab pegol to current therapy was associated with clinically meaningful reductions in fatigue and sleep problems, as well as improvements in pain and patient-assessed disease activity (PtGA) compared to the placebo group.2 Patient-reported outcomes such as fatigue, pain and sleep problems are common symptoms in RA.
At Week 12, significantly more patients in the certolizumab pegol group compared to the placebo group experienced improvements in fatigue (56.4% vs 46.2%, p<0.01), sleep problems (49.7% vs 42.5%, p=0.058), pain (59.0% vs 42.0%, p<0.001) and PtGA (59.5% vs 42.5%, p<0.001). Significant reductions in fatigue, pain and PtGA were recorded as early as Week 2 in the certolizumab pegol group.2
“These results demonstrate that the benefits of treatment with certolizumab pegol extend into areas that are meaningful for patients in terms of quality of life,” said Dr Janet Pope, Professor of the Department of Medicine, Division of Rheumatology and Epidemiology and Biostatistics at the University of Western Ontario, London, Ontario, Canada. “Factors such as fatigue, pain and sleep disturbance can have a significant impact on day-to-day life, so making a positive difference in these areas can be very significant for patients.”
Treatment with certolizumab pegol was generally well tolerated in the REALISTIC phase IIIb study population and subgroup analyses. Adverse and serious adverse event rates were comparable between certolizumab pegol and placebo treatment groups with no new safety signals observed through Week 12 and were not significantly different among patients with and without prior TNF inhibitor use. The most common adverse events were upper respiratory or urinary tract infections. The most common serious adverse events were infections and infestations. Of these, the most common serious infections were lower respiratory tract and lung infections.3
[1] Cimzia can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
[2] The analyses done by prior/no prior TNF inhibitor use were pre-specified; analyses by number and type of prior TNF inhibitors, monotherapy and number and type of concomitant DMARDs were post hoc.1
About REALISTIC
REALISTIC (RA Evaluation in Subjects Receiving TNF Inhibitor Certolizumab Pegol) is a multicenter phase IIIb trial in patients with active rheumatoid arthritis who have shown inadequate response to disease-modifying antirheumatic drugs, including patients with/without prior TNF-inhibitor exposure, with/without concomitant methotrexate or other disease-modifying anti-rheumatic drugs (DMARDs); and varying lengths of disease duration. The study demonstrated that – in a diverse group of RA patients reflecting those seen in daily clinical practice (including those with prior TNF-inhibitor use) – addition of Cimzia® to current therapy was associated with a rapid clinical response consistent in all strata, improved function and reduced disease activity.
A sub-analysis investigated Cimzia® as monotherapy or concomitantly with DMARDs in subgroups of patients with or without prior TNF inhibitor use. Active RA patients with inadequate response to ≥1 DMARD were randomised 4:1 to Cimzia® 400mg at Weeks 0, 2 and 4 followed by 200mg every 2 weeks or placebo injection (control) every 2 weeks + current therapy. Primary outcome was ACR20 at Week 12. Randomisation was stratified by prior TNF inhibitor use, concomitant use of methotrexate (MTX), and disease duration (<2 y vs ≥2 y). Treatment effect differences between subgroups were assessed by interactions (treatment by covariate) at 10% significance level.
Another sub-analysis determined the impact of Cimzia® on fatigue, sleep problems and other patient reported outcomes (PROs) in the REALISTIC study. Active RA patients with inadequate response to ≥1 DMARD were randomised 4:1 to CZP 400mg (n=851) at Weeks 0, 2 and 4 followed by 200mg every 2 weeks or placebo injection (control, n=212) every 2 weeks added to current therapy. PROs included fatigue (Fatigue Assessment Scale [FAS; 0–10 numeric rating scale]), sleep quantity and quality (Sleep Problem Index II domain of the Medical Outcomes Study sleep scale [MOS-SPI]), pain (0–100mm visual analogue scale [VAS]), and patient’s global assessment of disease activity (PtGA, 0–100mm VAS). The minimal clinically important difference (MCID) is a clinically relevant change in a patient’s status. The percentage of patients reporting MCIDs was determined: ≥1 for FAS, ≥6 for MOS-SPI, and ≥10mm for pain-VAS and PtGA. Correlations between PROs and DAS28 were also assessed (Pearson correlations [rho], CZP group only).
Cimzia® (certolizumab pegol) in European Union/ EEA important safety information
Cimzia® was studied in 2367 patients with RA in controlled and open label trials for up to 57 months. The commonly reported adverse reactions (1-10%) in clinical trials with Cimzia® and post-marketing were viral infections (includes herpes, papillomavirus, influenza), bacterial infections (including abscess), rash, headache (including migraine), asthenia, leukopaenia (including lymphopaenia, neutropaenia), eosinophilic disorder, pain (any sites), pyrexia, sensory abnormalities, hypertension, pruritis (any sites), hepatitis (including hepatic enzyme increase), injection site reactions. Serious adverse reactions include sepsis, opportunistic infections, tuberculosis, herpes zoster, lymphoma, leukaemia, solid organ tumours, angioneurotic edema, cardiomyopathies (includes heart failure), ischemic coronary artery disorders, pancytopaenia, hypercoagulation (including thrombophlebitis, pulmonary embolism), cerebrovascular accident, vasculitis, hepatitis/hepatopathy (includes cirrhosis), and renal impairment/nephropathy (includes nephritis). In RA controlled clinical trials, 5% of patients discontinued taking Cimzia® due to adverse events vs. 2.5% for placebo.
Cimzia® is contraindicated in patients with hypersensitivity to the active substance or any of the excipients, active tuberculosis or other severe infections such as sepsis or opportunistic infections, moderate to severe heart failure.
Before initiation of Cimzia®, evaluate patients for both active or inactive (latent) tuberculosis infection. Monitor patients for the development of signs and symptoms of infection during and after treatment with Cimzia®. If an infection develops, monitor carefully, and stop Cimzia® if infection becomes serious.
TNF blockers including Cimzia® may increase the risk: of reactivation of Hepatitis B Virus (HBV) in patients who are chronic carriers of the virus; of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease; of formation of autoantibodies and uncommonly of the development of a lupus-like syndrome; of severe hypersensitivity reactions. If a patient develops any of these adverse reactions, Cimzia® should be discontinued and appropriate therapy instituted.
With the current knowledge, a possible risk for the development of lymphomas, leukaemia or other malignancies in patients treated with a TNF antagonist cannot be excluded. Rare cases of neurological disorders, including seizure disorder, neuritis and peripheral neuropathy, have been reported in patients treated with Cimzia®.
Adverse reactions of the hematologic system, including medically significant cytopenia, have been infrequently reported with Cimzia®. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on Cimzia®. Consider discontinuation of Cimzia® therapy in patients with confirmed significant haematological abnormalities.
The use of Cimzia® in combination with anakinra or abatacept is not recommended due to a potential increased risk of serious infections. As no data are available, Cimzia® should not be administered concurrently with live vaccines or attenuated vaccines. The 14-day half-life of Cimzia® should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on Cimzia® should be closely monitored for infections.
Please consult the full prescribing information in relation to other side effects, full safety and prescribing information. European SmPC date of revision February 2011.
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001037/WC500069763.pdf
About CIMZIA®
Cimzia® is the only PEGylated anti-TNF (Tumor Necrosis Factor). Cimzia® has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha. Over the past decade, TNF-alpha has emerged as a major target of basic research and clinical investigation. This cytokine plays a key role in mediating pathological inflammation, and excess TNF-alpha production has been directly implicated in a wide variety of diseases. The U.S. Food and Drug Administration (FDA) has approved Cimzia® for reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy and for the treatment of adults with moderately to severely active rheumatoid arthritis. Cimzia® in combination with MTX, is approved in the EU for the treatment of moderate to severe active RA in adult patients inadequately responsive to disease-modifying antirheumatic drugs (DMARDs) including MTX. Cimzia® can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. UCB is also developing Cimzia® in other autoimmune disease indications. Cimzia® is a registered trademark of UCB PHARMA S.A.
About UCB
UCB, Brussels, Belgium (www.ucb.com) is a biopharmaceutical company dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Employing more than 9000 people in over 40 countries, UCB produced revenue of EUR 3.1 billion in 2009. UCB is listed on Euronext Brussels (symbol: UCB).
References
1. Weinblatt M et al. Certolizumab pegol as monotherapy or with concomitant DMARDs in patients with active rheumatoid arthritis (RA) with or without prior TNF inhibitor use: analyses of the REALISTIC 12-week Phase IIIb randomised controlled study. FRI0214
2. Pope J et al. Rapid reductions in fatigue and sleep problems, and correlation with improvements in patient-reported outcomes in patients with active RA treated with certolizumab pegol in the REALISTIC 12-week Phase IIIb randomised controlled study. THU0240
3. Weinblatt M et al. Efficacy and Safety of Certolizumab Pegol in a Clinically Representative Population of Patients With Active Rheumatoid Arthritis: Results of the REALISTIC Phase IIIb Randomized Controlled Study. 2010 American College of Rheumatology annual meeting
SOURCE: UCB
Post Views: 78
