Healthcare Industry News: Methotrexate
News Release - October 27, 2008
New Study Shows ENBREL(R) (etanercept) Is More Effective than a DMARD in the Treatment of Symptoms of Ankylosing Spondylitis PatientsData From Another Study Supported the use of ENBREL for up to Five Years in Ankylosing Spondylitis Patients
MAIDENHEAD, England, October 27 -- (Healthcare Sales & Marketing Network) -- New safety and efficacy data for active ankylosing spondylitis (AS) patients treated with ENBREL® (etanercept) were presented at the American College of Rheumatology (ACR) Scientific Meeting, 24-29 October, in San Francisco, CA: (1),(2)
- As discussed in an oral presentation, clinical data showed that ENBREL was effective in treating the signs and symptoms of active AS in significantly more patients than those receiving sulphasalazine, a disease modifying antirheumatic drug (DMARD) and significant differences were reported as early as 2 weeks. (Presentation #673, Oral Session) (1),(3)
- Data from a separate study presented at ACR showed that active AS patients treated with ENBREL experienced improvement in the signs and symptoms of their disease that were achieved and maintained for up to five years (252 to 264 weeks) of therapy. (Presentation #1119, Poster Board #380)(2)
AS, which affects between 0.1 percent to 1.4 percent of the worldwide population,(4) is a chronic, painful and progressive inflammatory disease affecting spine and joints, which can lead to loss of mobility, impaired physical function and postural deformity. It is characterised by persistent lower back pain and progressive stiffness of the spine.(5),(6) The diagnosis of AS is often delayed because inflammatory back pain can be mistaken for mechanical (common) back pain.(6) Unlike other forms of arthritis, AS frequently affects younger individuals and it tends to affect more men than women.(6)
Assessment of Etanercept and Sulphasalazine in Patients With Active AS(1)
This study was a randomized, double-blind clinical trial designed to compare the efficacy of ENBREL with sulphasalazine over 16 weeks in nearly 600 patients with active AS who had failed one or more non-steroidal anti-inflammatory drugs (NSAIDs) taken for at least three months.(3)
In this study, ENBREL was demonstrated to be more efficacious than sulphasalazine in helping patients to achieve improvement in pain, physical function and spinal mobility. These improvements were validated by multiple measures of efficacy and were seen at all time points throughout the study.(3)
At week 16, nearly 76 percent of the 378 patients treated with ENBREL achieved an ASAS 20 response, compared with 51 percent of the 187 patients who received sulphasalazine (p<0.001). Also at 16 weeks, nearly 60 percent of patients receiving ENBREL therapy achieved ASAS 40, versus nearly 33 percent of patients treated with sulphasalazine(p<0.001). The Assessment in Ankylosing Spondylitis (ASAS) is a composite measure of improvement in AS symptoms that includes total back pain, patient assessment of disease activity, inflammation and physical function. ASAS 20 or 40 response criteria represent an improvement of at least 20 percent or 40 percent in AS symptoms, respectively.
The study also showed that patients treated with ENBREL had an average 25 percent improvement in their BASMI score, versus 7 percent improvement in patients treated with sulphasalazine (p<0.001). The Bath Ankylosing Spondylitis Metrology Index (BASMI) is a composite measure of spinal and pelvic mobility that includes erectness of posture, neck rotation, forward flexion and side-to-side flexion of the lower spine, and outward movement of the legs at the hip joints. In addition, more than twice as many patients receiving ENBREL achieved Partial Remission than patients receiving sulphasalazine (p<0.001). Partial Remission is defined as a score of less than 20 on a one-hundred point scale on each of the four AS measures. (1)
Overall, patients treated with ENBREL achieved an average 48 percent improvement in physical function, as measured by the Bath Ankylosing Spondylitis Functional Index (BASFI), and these results were sustained through 16 weeks. Patients treated with sulphasalazine achieved an average 28 percent improvement during the same time period (p<0.001). The BASFI is a 10-question, patient self-assessment instrument consisting of 8 specific questions regarding physical function in AS and two questions reflecting the patient's ability to cope with everyday life. Each question is answered on a 10-cm horizontal visual analog scale, the average of which gives the BASFI score (0-10).(1)
In addition, patients treated with ENBREL achieved an average 54 percent improvement in disease activity, as measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Patients treated with sulphasalazine achieved an average 33 percent improvement (p<0.001). The BASDAI consists of a one through 10 scale that includes a daily activity composite and scores for fatigue, pain, discomfort, and stiffness.
No new safety signals were identified in this study. In the ENBREL group, seven people (1.8%) reported serious adverse events, compared with four people (2.1%) receiving sulphasalazine treatment. No cases of opportunistic infection, tuberculosis or demyelinating disease were reported with ENBREL in this study.
"Ankylosing spondylitis is a chronic disease causing a lot of back pain and decreased spinal mobility that may get progressively worse if not treated appropriately," said lead investigator Dr. Jürgen Braun, Medical Director, Rheumatology Medical Center, Ruhrgebiet, Herne, Ruhr-University, Bochum, Germany. "These data show that ENBREL may be an appropriate treatment option for AS patients because, as demonstrated in this study, it can be more effective than a traditional DMARD and work quickly to manage their symptoms and improve their mobility."
Five-Year Efficacy and Safety Data For Etanercept in Active AS(2)
A second study presented was designed to assess whether long-term safety, clinical efficacy, and patient-reported outcomes were sustained in AS patients receiving ENBREL from week 108 (baseline of this study) to week 264. This phase 4, 156-week open label extension study consisted of patients with AS who completed a 12-week randomized, placebo-controlled study followed by a 96-week open-label study. Results presented at ACR were from baseline of the randomized control trial through week 264 reporting data from active AS patients who received 252 to 264 weeks of continuous ENBREL therapy.
In patients with AS, continued ENBREL treatment resulted in improvements in clinical efficacy and patient-reported outcomes that were sustained for up to 264 weeks. Overall, of the 59 patients who were still in the trial, 75 percent (n=44) were ASAS20 responders at week 264. In addition, 66 percent (n= 39) of patients achieved a 50 percent improvement in their BASDAI score at the end of the study. The study also showed that improvements in patient-reported outcomes (patient global assessment, back pain, and morning stiffness) were sustained through 264 weeks of ENBREL treatment.
No new safety signals were reported throughout the study period. Myocardial infarction and cholelithiasis occurred in two patients. No cases of opportunistic infection, tuberculosis or demyelinating disease were reported with ENBREL in this study.
"These data show that treatment with ENBREL may provide AS patients with sustained improvement in their symptoms," said investigator Dr. Emilio Martin Mola, chief of the Rheumatology Department, Hospital La Paz, Madrid, Spain. "Since AS is a chronic disease that requires continuous treatment, these data are important to physicians who are considering a long-term therapy option for their patients."
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Notes to editors
About Ankylosing Spondylitis
AS is a chronic, painful and progressive inflammatory disease affecting the spine; it is a highly debilitating condition that tends to affect people before the age of 30, and is more common in men. (4)
In patients with AS, tissue is gradually replaced by fibrocartilage which then becomes ossified. When these lesions occur in the spine, it causes irreversible damage as the outer fibres are replaced by bone and the vertebrae become fused.(7)
The diagnosis of AS is commonly delayed by 8 to 11 years, after the onset of symptoms. Diagnosing AS early before irreversible damage has occurred is difficult as radiological proof of the disease is a late feature.(7)
Individuals with AS suffer pain and disability similar to that of patients with rheumatoid arthritis. Other symptoms include: lower back pain and stiffness, early morning stiffness and pain, bone tenderness and asymmetric arthritis of other joints and lower limbs.(7)
ENBREL is a fully human soluble tumour necrosis factor (TNF) receptor antagonist.
ENBREL is approved in the EU for the following indications:
ENBREL in combination with Methotrexate is indicated for the treatment of moderate to severe active rheumatoid arthritis in adults when the response to disease-modifying antirheumatic drugs, including Methotrexate (unless contraindicated), has been inadequate. ENBREL can be given as monotherapy in case of intolerance to Methotrexate or when continued treatment with Methotrexate is inappropriate. ENBREL is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with Methotrexate. ENBREL, alone or in combination with Methotrexate, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function.
Polyarticular juvenile idiopathic arthritis
Treatment of active polyarticular juvenile idiopathic arthritis (JIA) in children and adolescents aged 4 to 17 years who have had an inadequate response to, or who have proved intolerant of, Methotrexate. ENBREL has not been studied in children aged less than 4 years.
Treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate. ENBREL has been shown to improve physical function in patients with psoriatic arthritis, and to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease.
Treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.
Treatment of adults with moderate to severe plaque psoriasis who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, Methotrexate or PUVA.
The European Commission recently approved a new 50mg ENBREL once-weekly dosage regimen as an alternative to the currently approved 25mg ENBREL twice-weekly regimen for the treatment of patients with moderate-to-severe plaque psoriasis.
Important Safety Information(8)
Serious infections, including tuberculosis, and sepsis have been reported. Some of these infections have been fatal.
Do not start ENBREL in the presence of allergy to ENBREL or its components.
There have been rare reports of CNS demyelinating disorders, although the causal relationship to ENBREL remains unclear.
Rare cases of pancytopenia, and very rare cases of aplastic anemia, some fatal, have been reported in patients treated with ENBREL. Exercise caution in patients who have a previous history of significant hematologic abnormalities. Although the causal relationship to ENBREL remains unclear, advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. If significant hematologic abnormalities are confirmed, discontinue ENBREL.
Reports of malignancies affecting various sites have been received in the postmarketing period. Effects of ENBREL therapy on the development or course of infection and malignancy are unknown. In clinical trials of TNF antagonists, more cases of lymphoma were seen compared to control patients; however, the risk of lymphoma may be higher in RA patients.
Before initiation of therapy with ENBREL, any patient at increased risk for tuberculosis (TB) should be evaluated for active or latent infection. Prophylaxis of latent TB infection should be initiated prior to therapy with ENBREL. Applicable local guidelines should be consulted.
Reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus who are receiving anti-TNF agents, including ENBREL, has been reported. Patients at risk for HBV infection should be evaluated for prior evidence of the virus before initiating anti-TNF therapy. Although a causal relationship has not been established for ENBREL, caution should be exercised when administering ENBREL for patients identified as carriers for HBV.
There have been reports of worsening of hepatitis C in patients receiving ENBREL, although a causal relationship with ENBREL has not been established.
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1. Braun, J. et al. Assessment of Clinical Efficacy in a Randomized, Double-Blind Study of Etanercept and Sulphasalazine in Patients With Ankylosing Spondylitis. Abstract 08-A-2496-ACR from the American College of Rheumatology (ACR) Scientific Meeting in San Francisco, CA 24-29 October 2008.
2. Mola, E.M. et al. Five-Year Efficacy and Safety, Including Patient-Reported Outcomes, With Etanercept in Ankylosing Spondylitis. Abstract 08-A-591-ACR from the American College of Rheumatology (ACR) Scientific Meeting in San Francisco, CA 24-29 October 2008.
3. Final Abbreviated Report: A Randomized, Double-blind Study Evaluating the Safety and Efficacy of Etanercept and Sulphasalazine in Subjects with Ankylosing Spondylitis (ASCEND) CSR-72737.
4. Braun J. et al. Ankylosing spondylitis. Lancet. 2007 Apr 21;369(9570):1379-90. Review.
5. NY Presbyterian Hospital Website (Ankylosing Spondylitis). Last accessed at http://www.childrensnyp.org/mschony/fp/health/ankylosing-spondylitis.html on September 25, 2008.
6. Shaikh S. Ankylosing spondylitis: Recent breakthroughs in diagnosis and treatment. JCCA J Can Chiropr Assoc. 2007 Dec;51(4):249-60
7. Sieper J, Braun J et al. Ankylosing spondylitis: an overview. Ann Rheum Dis 2002; 61 (Supple III):iii8-iii18.
8. ENBREL EMEA SPC.
Source: Wyeth Pharmaceuticals
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