Poster abstracts
Methods: Data were analyzed from 2 double-blind, phase 3 trials
investigating the efficacy and safety of IXE in active PsA patients
(pts). For SPIRIT-1 [1] biologic disease-modifying antirheumatic
drug-naïve pts were randomized to placebo (PBO, n = 106) or
80 mg IXE every 4 wks (Q4W, n = 107) or every 2 wks (Q2W,
n = 103) post 160 mg starting dose. For SPIRIT-2 [2] (inadequate
responders to tumor necrosis factor inhibitors [TNFi]) pts were
randomized to PBO (n = 118) or 80 mg IXE Q4W (n = 122) or
Q2W (n = 123) post 160 mg starting dose. Minimal disease ac-
tivity (MDA), MDA very low disease activity (VLDA), Disease
Activity in Psoriatic Arthritis (DAPSA) LDA, DAPSA remission,
Psoriatic Arthritis Disease Activity Score (PASDAS) LDA, and
PASDAS VLDA composite endpoints were evaluated. Imputa-
tion for categorical responses was non-responder imputation.
Treatment comparisons (with placebo up to Wk 24) based on the
intent-to-treat population were made using a logistic regression
model. Data up to Wk52 are summarized.
Results: At Wk 24, percentage of pts achieving MDA (SPIRIT-P1
Q4W: 29.9; Q2W: 40.8; PBO: 15.1; SPIRIT-P2 Q4W: 27.9; Q2W:
31.9; PBO: 3.4), MDA VLDA (SPIRIT-P1 Q4W: 10.3; Q2W:
11.7; PBO: 0.9; SPIRIT-P2 Q4W: 12.3; IXEQ2W: 3.3; PBO: 0.8),
DAPSA LDA (SPIRIT-P1 Q4W: 31.8; Q2W: 34.0; PBO: 17.9;
SPIRIT-P2 Q4W: 25.4; Q2W: 27.6; PBO: 11.1), DAPSA remission
(SPIRIT-P1 Q4W: 15.9; Q2W: 24.3; PBO: 4.7; SPIRIT-P2 Q4W:
14.8; Q2W: 7.3; PBO: 0.8), PASDAS LDA (SPIRIT-P1 Q4W:
42.1; Q2W: 50.5; PBO: 18.9; SPIRIT-P2 Q4W: 39.3; Q2W: 35.0;
PBO: 6.8), and PASDAS VLDA (SPIRIT-P1 Q4W: 11.2; Q2W:
20.4; PBO: 1.9; SPIRIT-P2 Q4W: 13.1; Q2W: 7.3; PBO: 0.0) was
greater with Q4W and Q2W versus placebo.
Similarly, at Wk 52 the response rates were either sustained or
improved: MDA (SPIRIT-P1 Q4W: 39.3; Q2W: 36.9; SPIRIT-P2
Q4W: 34.4; Q2W: 23.6), MDA VLDA (SPIRIT-P1 Q4W: 14.0;
Q2W: 15.5; SPIRIT-P2 Q4W: 12.3; Q2W: 6.5), DAPSA LDA
(SPIRIT-P1 Q4W: 30.8; Q2W: 29.1; SPIRIT-P2 Q4W: 34.4; Q2W:
26.0), DAPSA remission (SPIRIT-P1 Q4W: 22.4; Q2W: 29.1;
SPIRIT-P2 Q4W: 18.9; Q2W: 11.4), PASDAS LDA (SPIRIT-P1
Q4W: 43.0; Q2W: 50.5; SPIRIT-P2 Q4W: 45.1; Q2W: 30.9), and
PASDAS VLDA (SPIRIT-P1 Q4W: 17.8; Q2W: 26.2; SPIRIT-P2
Q4W: 17.2; Q2W: 11.4).
Conclusions: Regardless of previous TNFi exposure, a higher
proportion of IXE-treated pts achieved MDA and MDA VLDA,
DAPSA LDA and DAPSA remission, and PASDAS LDA and
PASDAS VLDA at Wk 24 versus placebo. At Wk 52, the extent
of IXE clinical response sustained or further improved.
Reference:
1. Mease PJ et al. Ann Rheum Dis. 2017;76(1):79-87. 2. Nash P et al.
Lancet. 2017;389(10086):2317-2327.
P035
THE MACROPHAGE MODULATOR MP1032 SHOWS
SAFETY AND EFFICACY IN A HUMAN PHASE IIA
STUDY FOR THE TREATMENT OF MODERATE-TO-
SEVERE PLAQUE PSORIASIS
Petra Schulz, Astrid Kaiser, David Kosel, Sara Schumann, Wolf-
gang Brysch
MetrioPharm GmbH, Berlin, Germany
Introduction: MP1032 belongs to a new class of anti-inflammatory
drugs that modulate the redox state of activated macrophages.
MP1032 attenuates pro-inflammatory cytokine secretion in vivo
and in vitro and has pronounced disease-modifying effects in
various preclinical models.
Objectives: This randomized, double-blind, parallel, and placebo-
controlled trial aimed to evaluate pharmacokinetics, safety, and
efficacy of orally administered MP1032 in patients with moderate-
to-severe plaque psoriasis.
Methods: Forty-six patients with chronic plaque psoriasis (PASI >
10; disease duration ≥ 6 months) were equally randomized to
17
receive either 100 mg MP1032 or placebo by twice daily oral
administration. The study design consisted of a 42 day treatment
period with a follow-up of 28 days. Pharmacokinetic sampling
occurred on day 1 at 15, 30, 60, and 120 min post-dose. Adverse
events were coded according to the Medical Dictionary for Regu-
latory Activities. Efficacy parameters were assessed at screening
and on day 1, 15, 29, 43, 57, and 71.
Results: Enrolled patients had an average age of 40 years (21–65
years) and a median baseline PASI of 13.6 (ranging from 10.1 to
40.8). Pharmacokinetic evaluation demonstrated that MP1032
was rapidly absorbed, reaching maximum plasma concentrations
within 15 min after administration. Then, MP1032 plasma levels
were quickly declining, indicating a fast elimination. Safety
analysis did not reveal any clinically important safety issues. No
serious adverse events or deaths were reported and the incidence
of treatment emergent adverse events (TEAEs) between placebo
and the MP1032 treatment group was comparable. The majority
of TEAEs were mild to moderate in nature (mostly common cold,
headache, and itching). Analysis of clinical laboratory data and
vital signs did also not reveal any adverse effects of MP1032. After
only six weeks of treatment, MP1032 led to a PASI reduction of
about 25% in patients who entered the study with a PASI of 10–15.
In contrast, placebo administration reduced the respective PASI
only about 12%. During the four-week follow-up period, median
PASI scores in the MP1032 group trended back upward while the
placebo group remained unchanged, suggesting a positive thera-
peutic effect of MP1032. Since, patients with a lower basal PASI
had greater improvements during therapy than those with higher
scores, MP1032 seems to be a treatment option for patients with
mainly moderate psoriasis.
Conclusion: After six weeks of treatment, there was a clinically
relevant response in patients who entered the study with PASI
scores of 10–15. Overall, MP1032 demonstrated an excellent
safety profile and was well tolerated. Hence, redox modulation
targeted at the