Two multicenter, randomized, double-blind, placebo-controlled trials (PSOR-1 [NCT01194219] and PSOR-2 [NCT01232283]) enrolled a total of 1257 subjects 18 years of age and older with moderate to severe plaque psoriasis [body surface area (BSA) involvement of ≥ 10%, static Physician Global Assessment (sPGA) of ≥ 3 (moderate or severe disease), Psoriasis Area and Severity Index (PASI) score ≥ 12, candidates for phototherapy or systemic therapy]. Subjects were allowed to use low potency topical corticosteroids on the face, axilla and groin. Subjects with plaque psoriasis of the scalp were allowed to use coal tar shampoo and/or salicylic acid scalp preparations on scalp lesions.

Trial PSOR-1 enrolled 844 subjects and Trial PSOR-2 enrolled 413 subjects. In both trials, subjects were randomized 2:1 to OTEZLA 30 mg twice daily (BID) or placebo for 16 weeks. Both trials assessed the proportion of subjects who achieved PASI-75 at Week 16 and the proportion of subjects who achieved an sPGA score of clear (0) or almost clear (1) at Week 16. Across both trials, subjects ranged in age from 18 to 83 years, with an overall median age of 46 years. The mean baseline BSA involvement was 25.2% (median 21.0%), the mean baseline PASI score was 19.1 (median 16.8), and the proportion of subjects with an sPGA score of 3 (moderate) and 4 (severe) at baseline were 70.0% and 29.8%, respectively. Approximately 30% of all subjects had received prior phototherapy and 54% had received prior conventional systemic and/or biologic therapy for the treatment of psoriasis with 37% receiving prior conventional systemic therapy and 30% receiving prior biologic therapy. Approximately one-third of subjects had not received prior phototherapy, conventional systemic nor biologic therapy. A total of 18% of subjects had a history of psoriatic arthritis.

Clinical Response in Adult Subjects with Moderate to Severe Plaque Psoriasis

The proportion of subjects who achieved PASI-75 responses, and an sPGA score of clear (0) or almost clear (1), are presented in Table 8.

The median time to loss of PASI-75 response among the subjects re-randomized to placebo at Week 32 during the Randomized Treatment Withdrawal Phase was 5.1 weeks.

Plaque Psoriasis Involving the Scalp Area

A randomized, double-blind, placebo-controlled trial (PSOR-3 [NCT03123471]) was conducted in 303 adult subjects with moderate to severe plaque psoriasis of the scalp. Enrolled subjects had a Scalp Physician Global Assessment (ScPGA) score of ≥ 3, Scalp Surface Area (SSA) involvement of ≥ 20%, an inadequate response or intolerance to at least one topical therapy for plaque psoriasis of the scalp, and moderate to severe plaque psoriasis (BSA involvement of ≥ 10%, sPGA of ≥ 3 [moderate or severe disease], and PASI score ≥ 12).

Subjects were randomized 2:1 to receive either OTEZLA 30 mg twice daily (n =201) or placebo twice daily (n = 102) for 16 weeks. The primary endpoint was the proportion of subjects who achieved an ScPGA response at Week 16 (defined as ScPGA score of clear [0] or almost clear [1] with at least a 2-point reduction from baseline at Week 16). Secondary endpoints included the proportion of subjects with Whole Body Itch Numeric Rating Scale (NRS) response (defined as ≥ 4-point reduction from baseline) and the proportion of subjects with a Scalp Itch NRS response (defined as ≥ 4-point reduction from baseline).

Subjects had a mean age of 46.9 years, 61.7% were men and 75.6 % were white. At baseline, 76.9% of subjects had moderate plaque psoriasis of the scalp (ScPGA of 3), 23.1% had severe plaque psoriasis of the scalp (ScPGA of 4), 71.6% of subjects were biologic naïve, and 58.8% had failed 1 or 2 topical treatments. At baseline, the mean Whole Body Itch NRS score was 7.2 and the mean Scalp Itch NRS score was 6.7 with the scales ranging from 0 to 10. The mean baseline SSA involvement was 60.6% and the mean baseline BSA involvement was 19.8%.

The proportion of subjects who achieved an ScPGA response, Whole Body Itch NRS response, and Scalp Itch NRS response at Week 16 are presented in Table 9.

Figure 1 displays the proportion of subjects achieving Whole Body Itch NRS response at each visit, while Figure 2 displays the proportion of subjects achieving Scalp Itch NRS response at each visit.

Plaque Psoriasis Involving the Genital Area

A randomized, double-blind, placebo-controlled trial (PSOR-5 [NCT03777436]) was conducted in 289 adult subjects with moderate to severe plaque psoriasis of the genital area. Subjects had a modified static Physician Global Assessment of Genitalia (sPGA-G) score of ≥ 3 (moderate or severe), sPGA score of ≥ 3 (moderate or severe), and had an inadequate response or were intolerant to topical therapy for the treatment of plaque psoriasis of the genital area.

Subjects were randomized 1:1 to receive either apremilast 30 mg twice daily (n = 143) or placebo twice daily (n = 146) for 16 weeks. At Week 16, the placebo group was switched to receive OTEZLA and the OTEZLA group remained on drug through Week 32. The primary endpoint was the proportion of subjects who achieved a modified sPGA-G response (defined as a score of clear [0] or almost clear [1] with at least a 2-point reduction from baseline) at Week 16. Secondary endpoints included the proportion of subjects who achieved an sPGA response (defined as a score of clear [0] or almost clear [1] with at least a 2-point reduction from baseline) at Week 16 and the proportion of subjects who achieved at least a 4-point improvement in the 11-point Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) item score within the Genital Psoriasis Symptoms Scale (GPSS) at Week 16, among subjects with a baseline GPI-NRS score of ≥ 4.

Subjects ranged in age from 18-81 years, with a median age of 44 years. The proportions of subjects with a modified sPGA-G score of 3 (moderate) and 4 (severe) at baseline were 86.9% and 13.1%, respectively. The proportions of subjects with a sPGA score of 3 (moderate) and 4 (severe) at baseline were 88.6% and 11.1%, respectively. Baseline BSA involvement was < 10% for 57.4% of the subjects and ≥ 10% for 42.6% of the subjects. The mean baseline GPI-NRS score was 6.5. Of the enrolled subjects, 78.9% did not receive prior conventional systemic therapy and 84.4% were biologic-naïve.

The proportions of subjects who achieved a modified sPGA-G response, sPGA response, and GPI-NRS response are presented in Table 10.