Results from additional efficacy and safety analyses of Apremilast ( Otezla ) from the ESTEEM phase III clinical trial program were presented at the 23rd European Academy of Dermatology and Venereology ( EADV ) Congress in Amsterdam.
Apremilast is a selective inhibitor of phosphodiesterase 4 ( PDE4 ). PDE4 inhibition results in increased intracellular cAMP levels which is thought to indirectly modulate the production of inflammatory mediators. The specific mechanism(s) by which apremilast exerts its therapeutic action in patients with psoriasis or psoriatic arthritis is not well defined.
Apremilast is indicated for treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
An analysis of ESTEEM 2 has demonstrated that Apremilast significantly improved psoriasis in difficult-to-treat areas such as: the palms of the hands and feet ( known as palmoplantar psoriasis ), nails and scalp. Among patients who had nail psoriasis at baseline ( n=266 ), 45% treated with Apremilast 30 mg twice daily had at least a 50% improvement in this symptom at week 16, compared with 19% of those treated with placebo ( P less than 0.0001 ).
After 32 weeks of treatment with Apremilast 30 mg twice daily, 55% of patients achieved at least a 50% improvement.
Of those patients who had moderate to severe psoriasis on their palms and feet at baseline ( n=42 ), 65% had these symptoms reduced to clear or almost clear at week 16.
Improvements over baseline in nail, scalp and palmoplantar psoriasis were seen for up to 32 weeks.
An analysis of ESTEEM 1 and 2 found that Apremilast has improved skin discomfort / pain. Patients report that pruritus is one of the most common and bothersome symptoms of psoriasis. Significantly greater improvements in itching scores at week 16 were seen for patients treated with Apremilast 30 mg twice daily ( decreases of 31.5 in ESTEEM 1 and 33.5 in ESTEEM 2 ) compared with placebo ( decreases of 7.3 in ESTEEM 1 and 12.2 in ESTEEM 2; P less than 0.0001 for both trials ).
A post-hoc analysis found that improvements in itching and in skin discomfort/pain with Apremilast 30 mg twice daily were observed as early as week 2 and were maintained through week 32.
Long-term ( 52-week ) results from 411 patients in the ESTEEM 2 trial demonstrated durability of clinical responses achieved with Apremilast. For those patients who were treated with Apremilast 30 mg twice daily for 52 weeks and who achieved a 50% improvement in Psoriasis Area and Severity Index ( PASI ) at week 32, mean improvements in PASI remained stable between weeks 32 and 52 ( 74% to 77% ).
Analysis of data from ESTEEM 2 did not identify new or unexpected adverse events for patients treated with Apremilast, and the rate of adverse effects did not increase in frequency over time.
Adverse reactions reported in at least 5% of patients in any treatment group during the long-term 52-week Apremilast-exposure period include nausea, diarrhea, nasopharyngitis, tension headache, headache, vomiting, psoriasis, upper-respiratory tract infection, and back pain.
The discontinuation rate due to adverse reactions for those treated with Apremilast 30 mg twice daily for 52 weeks was approximately 7%.
No clinically meaningful changes in laboratory measurements were identified over the Apremilast 52-week exposure period.
ESTEEM 1 and 2 are two large pivotal phase III randomized, placebo-controlled studies evaluating Apremilast in patients with a diagnosis of moderate to severe plaque psoriasis for at least 12 months prior to screening, and who were also candidates for phototherapy or systemic therapy.
Approximately 1,257 patients were randomized 2:1 to receive either Apremilast 30 mg twice daily or placebo after an initial five-day titration period, for the first 16 weeks, followed by a maintenance phase from weeks 16-32 in which placebo patients were switched to Apremilast 30 mg twice daily through week 32, and a randomized withdrawal phase for responders from week 32 to week 52 based on their initial Apremilast randomization and Psoriasis Area and Severity Index ( PASI )-75 response.
Approximately 30% of all patients had received prior phototherapy and 54% had received prior conventional systemic and/or biologic therapy.
Approximately one-third of patients had not received prior phototherapy, conventional systemic nor biologic therapy.
A total of 18% of patients had a history of psoriatic arthritis. ( Xagena2014 )
Source: Celgene, 2014