Background/Purpose:
IL-23
is essential for the differentiation and maintenance of Th17 cells in psoriasis
and psoriatic arthritis (PsA). We assessed the efficacy and safety of the humanized
IgG1 monoclonal antibody BI 655066, which selectively inhibits IL-23p19, compared with
ustekinumab, an IL-12/23 inhibitor, in
patients with moderate-to-severe plaque psoriasis with and without concurrent
PsA.

Methods: In this
Phase 2 study (NCT02054481;
1311.02),
166 patients were randomly assigned (1:1:1:1 ratio) to receive subcutaneous
injections
of one of three dosage regimens of BI 655066 (18 mg single dose at Week 0; 90
or 180 mg at Weeks 0, 4, and 16), or ustekinumab (45 or 90 mg, based on weight,
at Weeks 0, 4, and 16). Skin lesions were assessed using the Psoriasis
Area and Severity Index (PASI) with the primary endpoint of PASI 90 (90%
improvement in PASI score from baseline) at Week 12. Pain was assessed by
visual analog scale (pain-VAS [0–100 mm]) at baseline (Week 0) and at Weeks 4,
12, and 24 in patients who had concurrent PsA. In this interim analysis, all
patients had completed the Week 24 visit.

Results: The
primary endpoint of PASI 90 response at Week 12 was achieved by 32.6% (14/43), 73.2%
(30/41), and 81.0% (34/42) of BI 655066 patients in the 18, 90, and 180 mg
groups, respectively, and 40.0% (16/40) of ustekinumab patients. A two-sided Cochran-Mantel-Haenszel
test of PASI 90 response at Week 12 between the 18, 90, and 180 mg groups of BI
655066, and ustekinumab, gave p-values of 0.4337, 0.0013, and <0.0001,
respectively. Among the 46 (27.7%) patients with PsA (either previously
diagnosed by rheumatologist [n=13] or suspected by investigator [n=33]), median
decreases from baseline in pain-VAS at Week 24 were 7.6%, 80.0%, and 86.5%, respectively,
for the BI 655066 18, 90, and 180 mg dose groups, compared with 77.6% for ustekinumab. The
criterion of >50% decrease
in pain-VAS (defined post hoc) at Week 24 was achieved in 16.7% (1/6), 81.8%
(9/11), and 90.9% (10/11) of patients in BI 655066 18, 90, and 180 mg dose groups,
respectively, compared with 57.1% (8/14) for ustekinumab. In the
BI 655066 90 and 180 mg dose arms the reductions in pain-VAS score were
observed as early as 4 weeks, and were highest at 24 weeks (Figure 1). AEs were similar
between treatment arms and there was no dose response relationship for any AE.
Seven patients reported serious AEs (four in the 18 mg and two in the 90 mg BI
655066 arms and one in the ustekinumab arm); all were considered unrelated to
study medication.

Conclusion: Selective
blockade of IL-23p19 with BI 655066, in the 90 mg and 180 mg arms, were associated
with PASI responses superior to ustekinumab in patients with
moderate-to-severe plaque psoriasis. Treatment with BI 655066 or
ustekinumab was associated with numeric improvement in pain-VAS in patients
with diagnosed or suspected PsA. Further studies are needed to assess long-term
efficacy and safety of BI 655066 in both psoriasis and PsA.