The Celgene Corporation today announced the results of two post hoc sub-analyses of clinical trials for OTEZLA^® (apremilast) at the 27^th European Academy of Dermatology and Venereology, EADV, Congress in Paris, France. Findings suggest OTEZLA offered meaningful improvements in outcomes important to patients with moderate to severe plaque psoriasis, which may not be captured by common measures of treatment efficacy that focus only on skin clearance, such as Psoriasis Area Severity Index (PASI) 75.

Plaque psoriasis is a multi-faceted disease that can manifest in numerous ways. Each patient has a different experience, and many are concerned about effects that go beyond the skin. This need for patient-centric care has been recognized by the World Health Organization – a shift in the focus from treating the skin lesions of psoriasis to addressing the needs of the whole patient.

“Only considering skin clearance may not fully capture the effect a treatment may have on an individual’s disease burden and its impact on daily life,” said Dr. Denis Jullien, Department of Dermatology and Venereology, Edouard Herriot Hospital, Lyon, France and an author of the study. “For example, itching, which is not accounted for by PASI, is cited by over a third of patients as their overriding quality-of-life issue. These new analyses of OTEZLA studies can help inform both prescribers and patients when evaluating treatment decisions.”

The findings include a new post hoc sub-analysis of the phase 3 ESTEEM 1 trial assessing clinical and quality-of-life outcomes for patients with moderate to severe plaque psoriasis who did not achieve PASI 75 (a 75 percent reduction in PASI) at either weeks 32 or 52, but continued OTEZLA treatment in this time period (n=203/844).

For patients who did not achieve a PASI 75 at weeks 32 or 52, more than half achieved a 50 percent reduction in PASI score (PASI 50) at weeks 32 and 52 following treatment with OTEZLA. This improvement, when taken together in disease-specific quality-of-life measures, may more reliably indicate clinically meaningful benefit. For example, itching, as measured by Visual Analogue Scale (VAS), was reduced from baseline by approximately 30 percent during weeks 4 to 52 in those patients (n=134) who were treated with OTEZLA from baseline and weeks 20 to 52 in patients (n=69) who were switched from placebo to OTEZLA at week 16. Quality of life, as measured by the Dermatology Life Quality Index (DLQI), was improved by at least 5 points in the two groups during the same time period.

Manifestations that are highly visible, such as scalp and nail psoriasis, can have a substantial effect on quality of life. A separate post hoc sub-analysis of the ESTEEM 1, 2 and UNVEIL studies examined changes in scalp and nail psoriasis, along with quality of life, following treatment with OTEZLA. The sub-analysis included patients who had nail psoriasis (n=768 in ESTEEM 1 and 2 and 73 in UNVEIL) or moderate to very severe scalp psoriasis (n=1,049 in ESTEEM 1 and 2 and 129 in UNVEIL) at baseline.

At week 32 in ESTEEM and UNVEIL, clearance of nail psoriasis [Nail Psoriasis Severity Index (NAPSI)=0] among patients receiving OTEZLA from baseline was achieved by 31.3 percent (n=146/466) and 36.2 percent (n=17/47) of patients, respectively. Among patients who were switched from placebo to OTEZLA at week 16, NAPSI clearance at week 32 was achieved by 15.5 percent (n=37/239) and 26.1 percent (n=6/23) of patients, respectively.

Among patients with moderate to severe scalp psoriasis at baseline, clear or minimal involvement of scalp psoriasis [Scalp Physician’s Global Assessment (ScPGA) response of 0 or 1] was achieved by greater proportions of patients receiving OTEZLA versus placebo at week 16 in both trials: 45.2 percent (n=351/694) versus 22.5 percent (n=80/355), respectively, in ESTEEM and 44.1 percent (n=30/68) versus 33.3 percent (n=23.3) in UNVEIL.

Of patients who had nail psoriasis or moderate to very severe scalp psoriasis at baseline, a DLQI of 0 or 1 was achieved by greater proportions of patients receiving OTEZLA versus placebo at week 16 [28.7 percent (n=206/719) versus 8.1 percent (n=29/358), respectively, in ESTEEM and 23.7 percent (n=23/97) versus 10.6 percent (n=5/47) in UNVEIL].

“The ESTEEM and UNVEIL clinical trials continue to provide important learnings about OTEZLA for the treatment of psoriasis as well as quality of life for people who live with this chronic condition,” said Volker Koscielny, Vice President Global Medical Affairs, Inflammation & Immunology at Celgene. “These sub-analyses of UNVEIL and ESTEEM suggest that appropriate patients with moderate to severe plaque psoriasis who experience manifestations beyond skin may benefit from treatment with OTEZLA.”

Psoriasis

Psoriasis affects 125 million people worldwide, including around 14 million people in Europe and 7.5 million people in the United States. It is a chronic and systemic inflammatory disorder, and is immune-mediated, meaning it is caused by an immune reaction in the body.

Psoriasis lesions can often be found on areas close to the joints such as the elbows and knees but can also appear on the scalp. Nail psoriasis affects up to 50 percent of people with psoriasis. Up to 84 percent of people with psoriasis experience itching, and over a third of patients actually cite itch as the most important factor contributing to their disease.

Around 75 percent of people living with psoriasis believe it has a negative impact on their quality of life and 83 percent of patients with psoriasis actively conceal the visible signs of their disease.

Esteem 

ESTEEM 1 and 2 are two large pivotal phase 3 randomized, placebo-controlled studies evaluating OTEZLA in patients with a diagnosis of moderate to severe plaque psoriasis for at least 12 months prior to screening, and who were also candidates for phototherapy and/or systemic therapy. Approximately 1,250 patients were randomized 2:1 to receive either OTEZLA 30 mg twice daily or placebo after an initial five-day titration period, for the first 16 weeks, followed by a maintenance phase from weeks 16-32 in which placebo patients were switched to OTEZLA 30 mg twice daily through week 32, and a randomized withdrawal phase for responders from week 32 to week 52 based on their initial OTEZLA randomization and Psoriasis Area and Severity Index (PASI) 75 response (ESTEEM 1) or (PASI) 50 (ESTEEM 2). A 5-year extension study of ESTEEM 1 and 2 is ongoing.

Unveil 

UNVEIL is the first prospective, randomized, controlled study to evaluate the clinical efficacy and safety of OTEZLA in patients with moderate plaque psoriasis (defined as a BSA involvement of 5-10 percent and sPGA of 3 based on a 0 to 5 scale) who were naïve to systemic and biologic therapies. Patients (n=221) were randomized 2:1 to receive either OTEZLA 30 mg twice daily or placebo for 16 weeks, followed by an open-label extension phase in which placebo patients were switched to OTEZLA through week 52. All doses were titrated over the first week of treatment. At baseline, more than 80 percent of patients had previously received topical therapy. The primary endpoint was the mean percentage change from baseline in the product of Physician’s Global Assessment (PGA) and BSA (percent) at week 16.

About OTEZLA^® (apremilast)

OTEZLA^® (apremilast) 30 mg tablets is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels, which is thought to indirectly modulate the production of inflammatory mediators. The specific mechanism(s) by which OTEZLA exerts its therapeutic action in patients is not well defined.

– Sept. 12, 2018 @ 18:39 GMT |