SUMMIT, N.J.—Celgene Corp. recently announced results of two post-hoc subanalyses of clinical trials for Otezla (apremilast) at the 27th European Academy of Dermatology and Venereology (EADV) Congress in Paris. 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.
According to Dr. Joshua Cirulli, director of global medical affairs for the dermatology operations at Celgene, “Psoriasis is a multifaceted, systemic inflammatory disease associated with skin lesions as well as pruritus and impairment in quality of life. The PASI score assesses the extent and severity of skin lesions, but does not capture pruritus or impairment in quality of life.”
Plaque psoriasis can manifest in a variety of ways, with each patient experiencing the disease differently. In fact, the World Health Organization has noted a need to shift focus from solely treating skin lesions of psoriasis to addressing all patients’ needs related to the disease.
“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, 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.”
Among the new findings is a post-hoc subanalysis of the Phase 3 ESTEEM 1 trial, looking at 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 weeks 32 or 52, but who still continued taking Otezla 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 PASI 50 at weeks 32 and 52, following treatment.
“PASI 50, or a 50-percent improvement in PASI score from baseline, is considered clinically meaningful,” Cirulli points out. “However, depending on the individual patient and severity of disease, greater reductions in PASI score may be needed.”
Such an improvement may more reliably signify clinically meaningful benefit, especially when considered alongside other quality-of-life metrics such as itching. Itching, or pruritus, as measured by the Visual Analogue Scale (VAS), was reduced from baseline by approximately 30 percent between 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.
Cirulli mentions that “According to prior research conducted by Reich et. al. published in Acta Derm [sic] 2013, an improvement in pruritus visual analog scale by 20 percent or more from baseline is considered clinically significant.”
Quality of life, as measured by the Dermatology Life Quality Index (DLQI), was improved by at least 5 points in the two groups in the span of weeks 4 to 52 in the aforementioned study. Explained Cirulli, “The minimal clinically important difference in the DLQI score is at least a 4-point change from baseline (Finlay et al, Clinical and Experimental Dermatology, 1994).”
Skin lesions or plaques on highly visible areas such as the nail or scalp can have a significant impact on a patient’s on quality of life. A separate post hoc sub-analysis of the ESTEEM 1, 2 and UNVEIL studies looked at changes in scalp and nail psoriasis, as well as 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 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.
Of the 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].
“Patients with psoriasis often present with multiple manifestations, such as skin lesions and scalp and nail psoriasis. This analysis has demonstrated that patients with scalp and nail psoriasis have a high impairment in quality of life, regardless of body surface area, and treatment with apremilast led to meaningful improvements in quality of life and scalp and nail psoriasis,” concludes Cirulli.