The COMFORT trial: piclidenoson versus apremilast for plaque psoriasis

Piclidenoson is a highly selective small molecule targeting the A3 adenosine receptor (A3AR) that is overexpressed in keratinocytes in patients with psoriasis, inhibiting interleukin (IL)-17 and IL-23 production. A3AR has low or no expression in normal cells.¹ Piclidenoson has shown promising anti-psoriatic effects in early clinical proof-of-concept phase II/III trials in moderate to severe plaque psoriasis.¹

At the European Academy of Dermatology and Venereology Congress 2022, Papp reported safety and efficacy results at Week 32 from the proof-of-concept phase III, randomized COMFORT trial of piclidenoson in patients with plaque psoriasis.

Study design²

The double-blind, randomized, placebo-controlled COMFORT trial included patients with moderate to severe plaque psoriasis randomized 3:3:3:2 to twice-daily treatment with either piclidenoson 2 mg, piclidenoson 3 mg, apremilast 30 mg, or placebo, with the placebo cohort re-randomized (1:1:1) to treatment after Week 16. The study duration was 32 weeks with an optional extension of up to 48 weeks. The trial design is shown in Figure 1.

Figure 1. Trial design* 

*Adapted from Papp et al.²

Results

Safety¹

Patients treated with piclidenoson exhibited fewer adverse events (AEs) than those treated with aprelimast, with a similar safety profile to the placebo group (Table 1). Of note was the difference in gastrointestinal (0.7% vs 6.3% for the piclidenoson 3 mg vs apremilast group, respectively) and nervous system disorder (0.7% vs 9.9% for the piclidenoson 3 mg vs apremilast group, respectively) AEs. In addition, the apremilast group had a higher discontinuation rate than the piclidenoson group.

Table 1. Occurrence of adverse events

Efficacy

Efficacy data included a total of 426 patients (piclidenoson 2 mg, n = 127; piclidenoson 3 mg, n = 103; apremilast 30 mg, n = 118; placebo, n = 78).² Piclidenoson 3 mg was superior to placebo at Week 16 (Figure 2a) but inferior to apremilast at Week 32 (Figure 2b).² However, patients treated with piclidenoson had comparable improvement in Psoriasis Disability Index from baseline to Week 32 compared with those treated with apremilast.¹ Additionally, response to piclidenoson was seen to increase over time for both Psoriasis Area and Severity Index 75 and Physician Global Assessment scores up to Week 32.¹

Figure 2. PASI 75 score at week 16 and week 32* 

PASI, Psoriasis Area and Severity Index.
*Adapted from Papp, et al.²

Conclusion

These findings demonstrate the superior efficacy of piclidenoson compared with placebo with statistically significant improvement in PASI 75 at week 16; however, it was shown to be comparable in efficacy to apremilast in patients with plaque psoriasis. The safety profile was acceptable, with fewer adverse events reported than those treated with apremilast and a significant reduction in gastrointestinal and nervous system disorder AEs.¹ The authors concluded that these results support the continued clinical development of piclidenoson, with a pivotal phase III trial is currently being planned.²