New Psoriasis Clinical Trial Demonstrates No Sustained Benefit Of Adding Topical Ointment To Abbott's HUMIRA(R) (adalimumab)

Main Category: Eczema / Psoriasis
Also Included In: Dermatology
Article Date: 05 May 2009 - 6:00 PDT

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Abbott has announced new data showing that HUMIRA® (adalimumab) is as effective in patients with moderate to severe psoriasis at 16 weeks with or without the concurrent use of topical therapy.1 The data also confirm that patients who did not have success with other systemic treatments were able to achieve a high response with HUMIRA.1 The results have been presented at the European Academy of Dermatology and Venereology (EADV) Spring Symposium in Bucharest, Romania and come from BELIEVE, the first major clinical trial to compare biologic therapy used in combination with a topical ointment to biologic therapy alone, in patients with moderate to severe psoriasis.

"Studies have previously demonstrated the safety and efficacy of HUMIRA monotherapy in the management of moderate to severe psoriasis, but in clinical practice some dermatologists may choose to supplement HUMIRA with a topical therapy," said Diamant Thaçi, M.D., director of clinical research at Goethe University Frankfurt and lead study investigator. "The new data from BELIEVE confirm that psoriasis can be effectively managed with HUMIRA without the simultaneous use of ointments, which patients often find to be messy and inconvenient."

Psoriasis is a non-contagious chronic disease affecting about 2% of the UK population.2 The most common form, chronic plaque psoriasis, which affects 80% of cases, appears as raised, red patches or lesions covered with a grey or silvery white buildup of dead skin cells, called scales or plaques.2 Elbows, knees and the scalp are the sites commonly affected.2 Psoriasis can profoundly impact all aspects of a patient's social and personal life as well as their work.3

In BELIEVE, patients in one arm of the study were treated with HUMIRA alone, while those in the other arm received a combination of HUMIRA and a topical treatment.1 Response rates were reported using the Psoriasis Area and Severity Index (PASI). PASI 75 is defined as a 75 percent improvement from baseline in the PASI score of a given patient.

HUMIRA provides dramatic response rates in patients who have failed previous systemic treatments. All patients had tried multiple systemic therapies prior to enrolling in the study; 70 percent had received methotrexate and nearly half had received another biologic drug.

During the first four weeks of the study, patients in both arms of the study improved rapidly, but patients receiving combination therapy improved more than patients on HUMIRA monotherapy. However, after four weeks, the use of a topical ointment in addition to HUMIRA did not offer any benefit compared to HUMIRA alone, with 71 percent of patients on monotherapy achieving PASI 75 at week 16.1 The high response rate seen in BELIEVE was consistent with the response rates seen in HUMIRA phase III clinical trials.4,5

"Most dermatologists in the U.K. are still experimenting with how to best use all of the treatment options available to them for psoriasis, which sometimes includes adding a topical therapy to a biologic," said Consultant Dermatologist Professor Chris Griffiths of the University of Manchester. "The BELIEVE study provides a new set of data that will help dermatologists maximise the efficacy of currently available therapeutics for psoriasis patients."

About BELIEVE

BELIEVE is a multi-centre, randomised, trial to assess the efficacy and safety of Adalimumab in Combination with Topical Treatment (Calcipotriol/Betamethasone) in Subjects with Moderate to Severe Psoriasis and Insufficient Response to Classic Systemic Treatment. The study was intended to reflect daily clinical practice. It included 730 patients from 15 countries, and was conducted in 133 centers. All patients in the trial received HUMIRA, with one arm receiving combination therapy (HUMIRA plus topical ointment), and the other arm receiving monotherapy (HUMIRA plus topical placebo).

BELIEVE included patients with prior TNF-antagonist experience and other biologic therapies. Subjects must have been treated and failed to respond to, or have a contraindication to, or be intolerant to at least two different systemic therapies. One of these systemic therapies must be cyclosporine or methotrexate or oral PUVA (psoralen and ultraviolet A radiation therapy).

About HUMIRA® (adalimumab)6

Adalimumab is an anti-tumour necrosis factor (anti-TNF) therapy. It is a human-sequence antibody, which functions to neutralise the biological function of tumour necrosis factor alpha (TNF-α) and mediate cell inflammation. The consequence of this action is efficacy against a number of auto-immune diseases of the skin, joints and intestines. Adalimumab is licensed in the UK to treat the following five immunological conditions:

Psoriasis6 HUMIRA is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA (psoralen and long-wave ultraviolet radiation).

Crohn's Disease6 Adalimumab is indicated for treatment of severe, active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.

For induction treatment, adalimumab should be given in combination with cortiocosteroids. Adalimumab can be given as monotherapy in case of intolerance to corticosteroids or when continued treatment with corticosteroids is inappropriate.

Ankylosing Spondylitis6

Adalimumab is indicated for the treatment of severe, active AS in adults who have had an inadequate response to conventional therapy.

Rheumatoid Arthritis6

Adalimumab in combination with methotrexate (MTX), is indicated for:

- the treatment of moderate-to-severe, active rheumatoid arthritis (RA) in adult patients when the response to disease-modifying anti-rheumatic drugs including MTX has been inadequate.
- the treatment of severe, active and progressive RA in adults not previously treated with MTX.

Adalimumab has been shown to reduce the rate of joint damage in RA as measured by X-ray and improve physical function, when given in combination with MTX. 6 Adalimumab can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate.

Psoriatic Arthritis6

Adalimumab is indicated for the treatment of active and progressive (PsA) in adults when the response to previous disease-modifying anti rheumatic drug therapy has been inadequate.

References:

1. Thaçi D et al. Efficacy and Safety of Adalimumab Plus Topical Therapy (Calcipotriol/Betamethasone) in the Treatment of Moderate to Severe Psoriasis - First Results of the BELIEVE Study. Academy of Dermatology and Venereology (EADV). April 2009

2. National Institute for Health and Clinical Excellence, Etanercept and efalizumab for the treatment of adults with psoriasis. Technology Appraisal Guidance T103. July 2006.

3. Kimball et al. The psychosocial burden of psoriasis. Am J Clin Dermatol. 2005;6(6): 383-392

4. Menter A et al. Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial. Acad Dermatol 2007; Published on-line: 10.1016/j.jaad.2007.09.010

5. Saurat Jet al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Brit J Dermatol 2007; Published on-line: DOI
10.1111/j.1365-2133.2007.08315.

6. Electronics Medicines Compendium HUMIRA (adalimumab) Summary of Product Characteristics. Available at: http://emc.medicines.org.uk/

Sources
Abbott