LIVERPOOL, ENGLAND – Further evidence that apremilast has multiple and sustained effects in psoriatic arthritis for at least 1 year were reported at the British Society for Rheumatology annual conference.
Data from two of the phase III studies that make up the PALACE (Psoriatic Arthritis Long-term Assessment of Clinical Efficacy) clinical trials program showed that the oral phosphodiesterase 4 inhibitor continued to suppress disease activity and improved pain and physical functioning associated with the skin and joint condition.
In the PALACE 1 (Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1) trial, 75 of 119 (63%) patients treated with apremilast 20 mg twice daily and 71 of 130 (55%) patients treated with apremilast 30 mg twice daily still had an American College of Rheumatology 20% (ACR20) response at 52 weeks.
Corresponding 52-week data from the PALACE 3 trial showed ACR20 responses in 56% of 116 patients and 62% of 127 patients for the two doses of apremilast, respectively. ACR50 and ACR70 were achieved by 25%-30% of patients, and 9%-10% achieved an ACR70.
Apremilast is marketed by Celgene as Otezla and gained approval from the Food and Drug Administration for the treatment of adults with active psoriatic arthritis in March. The FDA approval came with a caution that patients’ weight should be monitored regularly and that there had been increased reports of depression.
The long-term safety data from these two PALACE trials, however, showed no new safety concerns, according to the studies’ authors. The most common side effects seen were as reported previously and included diarrhea, nausea, and headache.
PALACE 1 and PALACE 3 were designed to assess the efficacy and safety of apremilast versus placebo in patients who had active psoriatic arthritis despite treatment with conventional nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) with or without additional biologic treatment.
For inclusion in the trials, patients had to have disease duration of at least 6 months, meet Classification of Psoriatic Arthritis (CASPAR) criteria, and have three or more tender or swollen joints involved. Patients enrolled in PALACE 3 also had to have skin involvement, with at least plaque psoriasis of 2 cm in size or larger.
A total of 504 patients were enrolled into PALACE 1 (Ann. Rheum. Dis. 2013;72[Suppl. 3]:163) and 505 into PALACE 3 and initially randomized to twice-daily treatment with placebo or one of two doses of apremilast for 24 weeks. At this point, all patients in the placebo arm who had not already been rerandomized to active treatment were randomized to apremilast 20 mg or 30 mg. Patients originally randomized to active therapy continued with their treatment if they continued to respond.
"I think what comes out of these [data], and looking over time, is that the effect is sustained with all the caveats that go with that because, of course, people only stay on [the drug] if they are doing well," PALACE 3 investigator Dr. Christopher Edwards observed in an interview.
Dr. Edwards, who is a clinical rheumatologist at University Hospital Southampton, England, noted that the statistical power of long-term extension studies is perhaps a little less robust than the initial study phases, but that these long-term data from the PALACE trials do seem to show that the effects of treatment with apremilast are sustained and maybe even that the effect size improves slightly over time.
Physical function, assessed via the Health Assessment Questionnaire–Disability Index (HAQ-DI), was improved with apremilast treatment in both the PALACE 1 and PALACE 3 trials. In the latter trial, mean change in HAQ-DI scores at 16 weeks declined by 0.13 and 0.19, compared with baseline values in the apremilast 20-mg and 30-mg groups. In contrast, scores increased by 0.07 in the placebo group. Over the following year, HAQ-DI scores continued to improve, with the mean change in scores from baseline crossing the threshold of –0.30, which many think signifies a clinically meaningful change, Dr. Edwards explained.
HAQ-DI scores in PALACE 1 at 52 weeks were a respective –0.369 and –0.318 in the 20-mg and 30-mg groups, and at the 16-week assessment point, they had been –0.20 and –0.24, respectively, and –0.09 for placebo.
Furthermore, in the PALACE 3 trial, 29%-39% of patients treated with apremilast achieved a 75% improvement in skin involvement, assessed via the Psoriasis Area and Severity Index (PASI) at 1 year. PASI50 was achieved in 49%-54%.
Dr. Edwards observed that some of the additional data now available from PALACE 3 showed that there was a beneficial effect of apremilast on enthesitis and dactylitis – two unique features of psoriatic arthritis that are often not treated by the use of the nbDMARDS, such as methotrexate and sulfasalazine.