ESTEEM 1 is the largest of two registrational, randomized, placebo-controlled studies evaluating apremilast, an oral small-molecule specific inhibitor of phosphodiesterase 4 (PDE4), in more than 1,200 patients with moderate-to-severe plaque psoriasis. Previously reported findings from ESTEEM 1 showed that apremilast significantly improved general signs and symptoms of psoriasis across a wide-range of patient types.
“Up to 55 percent of patients with psoriasis at any given time have nail
involvement, and more than half have scalp psoriasis, which can be
particularly debilitating for individuals dealing with this
difficult-to-treat disease,” said Professor
New analyses (abstract #2033) assessed the effects of apremilast on 558 patients in ESTEEM 1 with nail psoriasis and on 563 patients with at least moderate scalp psoriasis.
After 16 weeks of treatment, patients in the apremilast 30 mg twice daily (BID) group had significantly greater improvements in the Nail Psoriasis Severity Index (NAPSI) scores than the patients treated with placebo, showing an improvement of 22.5% vs. a worsening of 6.5%, respectively; P<0.0001. Improvements continued through 32 weeks of treatment for those patients on apremilast 30 mg BID (an improvement of 43.6%).
Psoriasis of the scalp, another difficult-to-treat area, was also improved by treatment with apremilast 30 mg BID. After 16 weeks of therapy, significantly more patients treated with apremilast 30 mg achieved a ScPGA score of 0-1 (clear or almost clear) compared with those in the placebo group (46.5% vs. 17.5%, respectively; P<0.0001). This effect was generally maintained for those patients who remained on apremilast through week 32.
As shown in a separate analysis (abstract #0237), the treatment of 844
patients in ESTEEM 1 with apremilast also significantly improved
health-related quality-of-life, as assessed by a variety of standardized
measurements, including the Dermatology Quality of Life Index (DLQI),
the Patient Health Questionnaire (PHQ-8), the European Quality of Life 5
Dimensions Questionnaire (EQ-5D), and the 36-item
Significant improvements in these measurement tools were seen after 16 weeks of treatment with apremilast; improvements were maintained through 32 weeks of treatment. Patients initially treated with placebo for 16 weeks who were then treated with apremilast for a subsequent 16 weeks also showed improvements in these measures.
In these analyses, the overall safety and tolerability profile of apremilast in patients with moderate to severe psoriasis was consistent with previously reported findings. The most commonly observed adverse events included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. Adverse events were generally mild to moderate in severity. Nausea, vomiting, and diarrhea tended to occur most frequently during the first week of dosing and subsequently decreased. The discontinuation rate due to these AEs was low.
A New Drug Application (NDA) to the
Earlier this year,
About ESTEEM 1 and 2
ESTEEM 1 and 2 are two large pivotal phase III randomized, placebo-controlled studies evaluating apremilast in subjects with a diagnosis of moderate to severe plaque psoriasis for at least 12 months prior to the screening, and at baseline, and who were also candidates for phototherapy and/or systemic therapy. Approximately 1,250 patients were randomized 2:1 to receive either apremilast 30 mg BID or placebo for the first 16 weeks, followed by a maintenance phase from weeks 16-32 in which placebo subjects were switched to apremilast 30 mg BID through week 32, and a randomized withdrawal phase for responders from Week 32-Week 52 based on their initial apremilast randomization and PASI response.
Apremilast, an oral small-molecule specific inhibitor of phosphodiesterase 4 (PDE4), intracellularly modulates a network of pro-inflammatory and anti-inflammatory mediators. PDE4 is a cyclic adenosine monophosphate (cAMP)-specific PDE and the dominant PDE in inflammatory cells. PDE4 inhibition elevates intracellular cAMP levels, which in turn down-regulates the inflammatory response by modulating the expression of TNF-α, IL-23, and other inflammatory cytokines. Elevation of cAMP also increases anti-inflammatory cytokines such as IL-10.
Psoriasis is an immune-mediated, non-contagious chronic inflammatory
skin disorder of unknown cause. The disorder is a chronic recurring
condition which varies in severity from minor localized patches to
complete body coverage. Plaque psoriasis is the most common type of
psoriasis. About 80 percent of people who develop psoriasis have plaque
psoriasis, which appears as patches of raised, reddish skin covered by
silvery-white scales. These patches, or plaques, frequently form on the
elbows, knees, lower back, and scalp. Psoriasis occurs nearly equally in
males and females. Recent studies show that there may be an ethnic link.
Psoriasis is believed to be most common in Caucasians and slightly less
common in other ethnic groups. Worldwide, psoriasis is most common in
Scandinavia and other parts of northern
Celgene International Sàrl, located in Boudry, in the
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Source: Celgene International Sàrl