Multinational Pristine Trial Findings Demonstrate Burden Of Moderate-To-Severe Plaque Psoriasis, And The Efficacy Profile Of Etanercept Treatment

Main Category: Eczema / Psoriasis
Also Included In: Dermatology
Article Date: 10 Sep 2010 - 1:00 PDT

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Data from a multinational study demonstrate that etanercept effectively treats moderate-to-severe plaque psoriasis, with a significant mean improvement from baseline in Psoriasis Area and Severity Index (PASI) of up to 82 percent at week 24.1 The findings, presented at the 40th Annual European Society for Dermatological Research (ESDR) meeting, are from the PRISTINE (PsoRiasis study to assess effIcacy and SafeTy IN subjects taking Etanercept 50 mg once weekly and twice weekly with adjunct therapy) trial, a multi-center, randomized, double-blind study evaluating the efficacy and safety of two dose regimens of etanercept used with adjunctive topical therapies.2 With more than 18 years of collective clinical experience, etanercept offers physicians and patients an established efficacy and safety profile in managing several inflammatory diseases.3,4

The PRISTINE trial included 273 patients (≥18 years) with active, clinically stable, moderate-to-severe, chronic plaque psoriasis from 32 sites across Europe, Latin American and Asia.1,2 Treatment efficacy was determined by improvement in PASI scores, an accepted standard to measure skin disease activity.1 Additional predefined exploratory analyses of PRISTINE were conducted to evaluate the presence of several cardio-metabolic biomarkers in the randomized population.2 Findings from the baseline measures demonstrate that patients with moderate-to-severe plaque psoriasis experience a significantly increased risk for a variety of cardio-metabolic conditions, including obesity, metabolic syndrome, diabetes, chronic kidney disease, hypertension, and overall inflammation.2

"These findings illustrate that the complexity of psoriasis goes well beyond the skin disease. Given the significant disease burden of psoriasis, it is important that co-morbid illnesses are adequately identified and addressed in clinical practice," said Dr. Robert Strohal, associate professor and board-certified dermatologist and Head of the Department of Dermatology and Venerology at the Federal University Teaching Hospital Feldkirch (Austria). "PRISTINE also provides further evidence of the efficacy and safety profile of etanercept in treating moderate-to-severe psoriasis, with more than half of etanercept treated patients reporting 'clear' or 'almost clear' skin response, and nearly 80 percent achieving a PASI 75 response."1

In the trial, patients were randomized in a 12-week double-blind phase to either 50 mg once weekly (OW) or 50 mg twice weekly (BIW) with stable doses of mild topical therapies to the scalp, axillae and groin only, as in the pivotal studies.1 During weeks 12 to 24, all patients received etanercept 50 mg OW with use of all doses of topical agents liberalized at the discretion of physician in concert with the patient.1

At week 24, 61 percent in the OW group and 78 percent in the BIW group achieved a PASI 75, and 32 percent and 48 percent, respectively, achieved a PASI 90.1 Overall, the mean percentage improvement from baseline in PASI to week 24 was 71 percent in the OW/OW group and 82 percent in the BIW/OW group.1 In addition, 50 percent in OW/OW and 69 percent in BIW/OW reported "clear" or "almost clear" skin responses on the Physician Global Assessment (PGA) of psoriasis with minimal use of concomitant potent topical medications after 24 weeks.1

A total of seven serious adverse events occurred: four in the OW group and three in the BIW group.1 No new safety signals were observed in the PRISTINE trial.1

These results support previous findings from the CRYSTEL (Clinical Randomized Year-long STudy assessing the safety and efficacy of EnbreL in Psoriasis), which demonstrated that etanercept offers psoriasis patients reliable and sustainable skin clearance.4,5

Cardio-metabolic characteristics in psoriasis patients

Psoriasis is a common chronic inflammatory skin disorder that has a substantial impact on daily living. Psoriasis has also been associated with systemic co-morbidities, e.g., obesity, hyperlipidemia, diabetes, hypertension, and cardiovascular disease, which may be inadequately detected in clinical practice.6,7

At the start of the PRISTINE trial, 39 percent of patients were identified as having metabolic syndrome(which comprises co-occurring risk factors that increase the risk for type 2 diabetes, coronary artery disease, and stroke), which is higher than recent global estimates of 20 to 30 percent for the general population.2,8 Among the patients who met the criteria for metabolic syndrome at baseline, 71 percent had elevated waist circumference, 27 percent had low HDL cholesterol, 37 percent had elevated triglycerides, 36 percent had elevated blood pressure, and 35 percent had diabetes.2

About Etanercept9

Etanercept is a fully human soluble tumor necrosis factor (TNF) receptor antagonist. Etanercept was first approved in 1998 for moderate-to-severe active rheumatoid arthritis and has over 18 years and 2 million patient-years of collective clinical experience. Etanercept in the EU is approved for the following indications:

- Rheumatoid arthritis: Etanercept 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. Etanercept can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. Etanercept is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. Etanercept, 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. Etanercept has not been studied in children aged less than 4 years.

- Psoriatic arthritis: Treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate. Etanercept 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.

- Ankylosing spondylitis: Treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.

- Plaque psoriasis: 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 etanercept once-weekly dosage regimen as an alternative to the currently approved 25mg etanercept twice-weekly regimen for the treatment of patients with moderate-to-severe plaque psoriasis.

- Pediatric plaque psoriasis: Treatment of chronic severe plaque psoriasis in children and adolescents from the age of 8 years who are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies. For full information about etanercept go here-

Important Safety Information

Serious infections, including sepsis and tuberculosis, have been reported with the use of etanercept. Some of these infections have been fatal. These infections were due to bacteria, mycobacteria, fungi, and viruses. Opportunistic infections have also been reported. Patients who develop a new infection while undergoing treatment with etanercept should be monitored closely. Administration of etanercept should be discontinued if a patient develops a serious infection.

Caution should be exercised when considering the use of etanercept in patients with a history of recurring or chronic infections or underlying conditions which may predispose patients to infections. Treatment with etanercept should not be initiated in patients with sepsis or risk of sepsis, or in patients with serious active infections.

Before initiation of therapy with etanercept, 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 etanercept. Physicians should monitor patients receiving etanercept for signs and symptoms of active TB, including patients who tested negative for latent tuberculosis infection. Applicable local guidelines should be consulted.

Reports of malignancies affecting various sites have been received in the postmarketing period. In clinical trials of TNF antagonists, more cases of lymphoma were seen among patients receiving a TNF antagonist compared to control patients. However, there is an increased background lymphoma risk in RA patients with long-standing, highly active, inflammatory disease. Combining the results of controlled portions of clinical trials of etanercept, more cases of non-melanoma skin cancer were seen in patients receiving etanercept compared with control patients, particularly in patients with psoriasis. A possible risk for the development of lymphomas or other malignancies in patients treated with an anti-TNF agent cannot be excluded.

Do not start etanercept in patients with hypersensitivity to etanercept or its components. Allergic reactions associated with etanercept administration have been reported. If any serious allergic or anaphylactic reaction occurs, discontinue administration of etanercept immediately. There have been rare reports of CNS demyelinating disorders in patients treated with etanercept.

Rare cases of pancytopenia, and very rare cases of aplastic anemia, some fatal, have been reported in patients treated with etanercept. Exercise caution in patients who have a previous history of blood dyscrasias. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. If blood dyscrasias are confirmed, discontinue etanercept.

Reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus who are receiving anti-TNF agents, including etanercept, 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 etanercept, caution should be exercised when administering etanercept for patients identified as carriers for HBV.

There have been reports of worsening of hepatitis C in patients receiving etanercept, although a causal relationship with etanercept has not been established.

Physicians should use caution when using etanercept in patients who also have moderate to severe alcoholic hepatitis.

References

1. Etanercept ESDR abstract: Efficacy and safety of etanercept for the treatment of moderate-to-severe psoriasis when used with adjunctive topical therapy as needed: the PRISTINE trial.

2. Etanercept ESDR abstract: Baseline Cardiometabolic Characteristics of Moderate-to-Severe Plaque Psoriasis Subjects in the PRISTINE Trial.

3. Husted JA, et al. Validating the SF-36 health survey questionnaire in patients with psoriatic arthritis. J Rhuematol. 1997; 24:511-17.

4. Data on file, Pfizer Inc.

5. Ortonne J-P, et al. Efficacy and safety of continuous versus paused etanercept treatment in patients with moderate-to-severe psoriasis over 54 weeks: The CRYSTEL study. Expert Rev. Dermatol. 2008;3(6):657-665

6. Azfar RS, et al. Psoriasis and metabolic disease: epidemiology and pathophysiology. Curr Opin Rheumatol. Jul 2008;20(4):416-422.-9-

7. Gelfand JM, et al. The risk of mortality in patients with psoriasis: results from a population-based study. Arch Dermatol. Dec 2007;143(12):1493-1499.

8. Grundy SM. Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol. Apr 2008;28(4):629-636.

9. Etanercept Summary of Product Characteristics. . Accessed September 7, 2010.

Source:
Pfizer Inc

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