New data presented today at EULAR 2013, the Annual Congress of the European League Against Rheumatism show that apremilast administered to patients with psoriatic arthritis continues to demonstrate meaningful clinical responses beyond 24 weeks. For patients who completed 52 weeks of the study, up to 65% achieved ACR20* response rates. Also, apremilast continued to be well tolerated with an acceptable longer-term safety profile.
Apremilast is a novel, oral small-molecule inhibitor of phosphodiesterase 4 (PDE4). It works as an anti-inflammatory drug by modulating a network of pro- and anti-inflammatory mediators inside cells.
PsA is a chronic inflammatory arthritis associated with psoriasis which significantly impacts health-related quality of life in patients, and increases risk of co-morbid cardiovascular and gastrointestinal disease.2 Psoriasis occurs in 2-3% of the population, with PsA occurring in up to 30% of those of cases.3
"Over the course of their disease patients with psoriatic arthritis may take a variety of treatment regimens over extended periods of time. Durability of response is therefore important. This relatively large study suggests that apremilast has sustained efficacy and tolerability over a year among patients previously treated with DMARDs and/or biologic agents" said Dr Arthur Kavanaugh, Professor of Medicine at the University of California, San Diego. "These results show that apremilast may become a potential therapy for psoriatic arthritis patients," he added.
PALACE-1 is a phase III multi-centre, double-blind, placebo-controlled, parallel-group study with two active-treatment groups. 504 patients with active psoriatic arthritis, despite prior disease-modifying anti-rheumatic drugs (DMARDs) and/or biologicals over the previous 24 weeks were randomised 1:1:1 to receive either apremilast 20 mg twice daily, 30 mg twice daily or identically-appearing placebo for 24 weeks.
The primary endpoint of the study was the proportion of patients in each treatment group who achieved ACR20 compared to baseline at week 16. Secondary endpoints included other measures of symptoms and signs, physical function and patient-reported outcomes.
At week 16, significantly more apremilast 20mg (31.3%; P=0.0140) and apremilast 30mg patients (40.0%; P<0.0001) achieved an ACR20 vs. placebo (19.4%). At week 52, by which time all patients had received a minimum of 28 weeks treatment with apremilast, response was generally maintained over the treatment period. At week 52, ACR20 was achieved by 63.0% (apremilast 20mg) and 54.6% (apremilast 30mg) of patients.
At week 16, patients in the placebo group with <20% reduction in swollen/tender joints were re-randomised to apremilast 20mg or apremilast 30mg; placebo patients with ≥20% reduction in swollen/tender joints at week 16 were re-randomised to apremilast 20mg or apremilast 30mg at week 24; patients receiving apremilast remained on their initial dose. At week 24, all remaining placebo patients were re-randomised to apremilast 20mg or apremilast 30mg through to week 52.
Exposure-adjusted incidence rates for adverse events (AEs), severe AEs, and serious AEs were comparable between 0-24 and 0-52 wks. The proportion of patients remaining on apremilast to week 52 who first reported the most common GI disturbances (e.g., diarrhoea, nausea, and vomiting) after week 24 was low (ranging from 0.6-3% for apremilast 20mg and 0-1.8% for apremilast 30mg). There were no clinically meaningful laboratory findings with exposure up to 52 weeks.
No safety signals with respect to major cardiac events, malignancies, and opportunistic infections were observed, consistent with the 0-24 week period. No cases of lymphoma, tuberculosis, or tuberculosis reactivations were reported for the 52-week period.
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More information: * ACR (American College of Rheumatology) criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters: acute phase reactant (such as sedimentation rate), patient assessment, physician assessment, pain scale and disability/functional questionnaire. ACR20 refers to a 20% improvement in tender/swollen joint counts, as well as in three of the five criteria.
1.Kavanaugh A et al., Long-term (52-week) results of a phase 3, randomized, controlled trial of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis [abstract]. EULAR Annual European Congress of Rheumatology; 12-15 June 2013; Madrid, Spain. Abstract nr. LB0001.
2.Gladman DD. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005; 64:ii14-ii17
3.About psoriasis, National Psoriasis Foundation. Available at: www.psoriasis.org/learn_statistics. Last accessed May 2013