An exploratory analysis suggested improvements in itching observed at week 16 were also maintained at week 52 in patients in both groups
No new safety signals or clinically meaningful changes in laboratory values for OTEZLA identified through week 52
"Many patients with moderate to severe plaque psoriasis need treatment options that can help in managing multiple facets of the disease, including itching and impact on disease-related quality of life," said
The LIBERATE study evaluated the clinical efficacy and safety of either oral OTEZLA 30 mg twice daily or weekly subcutaneous (SC) etanercept 50 mg compared with placebo at week 16 in 250 patients who had no prior exposure to a biological therapy. It also examined the relative safety of a switch from etanercept to OTEZLA after week 16 during an open label extension phase. Primary findings were previously presented at the 73rd Annual Meeting of the
As shown at AAD, at week 16, 40 percent (33/83) of patients receiving OTEZLA 30 mg twice daily demonstrated statistically significant and clinically meaningful improvements compared with 12 percent (10/84) of patients on placebo in the primary endpoint, Psoriasis Area and Severity Index (PASI)-75 response (P < 0.0001). Statistical significance was also achieved for patients receiving weekly injections of etanercept 50 mg compared with placebo [48 percent (n=40/83) vs. 12 percent (n=10/84), respectively, P < 0.0001].
New findings presented at EADV showed that 51 percent (42/83) of patients randomized to OTEZLA at baseline and 55 percent of patients who switched from etanercept to OTEZLA at week 16 (46/83) achieved
Based on an exploratory analysis, OTEZLA also improved pruritus (itching), one of the most common and bothersome symptoms of psoriasis, as measured by a visual analog scale (0 mm=no itch at all; 100 mm=worst itch imaginable). Significantly greater improvements in itching scores were seen at week 16 for patients treated with OTEZLA 30 mg twice daily (decrease of 38 mm; 95% confidence interval [CI]: -45 to -31 mm) compared with placebo (decrease of 26 mm; CI: -34 to -19 mm). Improvement in pruritus was observed as early as week 2 in patients receiving OTEZLA. Lower itching scores were also observed in patients who received weekly injections of etanercept 50 mg from baseline to week 16.
Improvements in itching were maintained from week 16 to week 52 (decrease of 36 mm) in patients who received OTEZLA from baseline and in patients who switched from etanercept to OTEZLA at week 16 (decrease of 35 mm).
Treatment with OTEZLA 30 mg twice daily also significantly improved disease-related quality of life (a secondary endpoint) at week 16 compared with placebo. OTEZLA showed a mean improvement from baseline in total Dermatology Life Quality Index (DLQI) score (decrease of 8.7; CI: -10.5 to -6.9) vs. placebo (decrease of 4.9; CI: -6.1 to -3.7) at week 16. A decrease in total DLQI scores was also observed for patients who received weekly injections of etanercept 50 mg from baseline to week 16.
Total DLQI scores were maintained from week 16 to week 52 in patients who received OTEZLA from baseline (decrease of 8.9; CI: -10.8 to -7.0) and in patients who switched from etanercept to OTEZLA at week 16 (decrease of 8.0; CI: -9.7 to -6.4).
The safety and tolerability data for OTEZLA observed in the LIBERATE study were generally consistent with previously reported data from six other phase III studies of OTEZLA in psoriasis or psoriatic arthritis; no new safety signals were observed. Adverse events reported in at least five percent of patients taking OTEZLA in the LIBERATE study were diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, headache and tension headache. No new safety or tolerability issues were observed through week 52 in patients who switched from etanercept to OTEZLA at week 16.
The LIBERATE study is ongoing.
The views expressed and the techniques presented by the speakers at the 24th
LIBERATE (PSOR-010; EvaLuatIon from a PlaceBo-controllEd Study of ORal ApremilasT and Etanercept in Plaque Psoriasis) is a phase IIIb, multicenter, randomized, placebo-controlled, double-blind, double-dummy study of the efficacy and safety of OTEZLA, etanercept and placebo, in subjects with moderate to severe plaque psoriasis. The primary objective of the LIBERATE study was to evaluate the clinical efficacy and safety of oral OTEZLA 30 mg twice daily compared with placebo at week 16. Secondary objectives of the study included: the evaluation of the clinical efficacy and safety of etanercept 50 mg SC once weekly (QW) compared with placebo at week 16 and the evaluation of the relative safety of a crossover from etanercept to OTEZLA 30 mg twice daily, as compared with OTEZLA dosed since week 0, after week 16. Subjects were required to have inadequate response, intolerance or contraindication to at least one conventional systemic agent and no prior exposure to biologics. The study enrolled 250 subjects who were randomized 1:1:1 to receive OTEZLA 30 mg twice daily, etanercept 50 mg QW or placebo, for 16 weeks. Following the first 16 weeks, all subjects were switched to (or continued on) OTEZLA 30 mg twice daily through week 104. The primary endpoint was the proportion of subjects with either OTEZLA 30 mg twice daily or placebo who achieved
OTEZLA is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). 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 OTEZLA exerts its therapeutic action in patients with psoriasis or psoriatic arthritis is not well defined.
OTEZLA is approved:
Important Safety Information (based on US labeling)
Otezla® (apremilast) is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation.
Warnings and Precautions
Depression: Treatment with OTEZLA is associated with an increase in adverse reactions of depression. During clinical trials, 1.0% (10/998) of patients treated with OTEZLA reported depression or depressed mood compared to 0.8% (4/495) treated with placebo; 0.3% (4/1441) of patients treated with OTEZLA discontinued treatment due to depression or depressed mood compared with none in placebo treated patients (0/495). Depression was reported as serious in 0.2% (3/1441) of patients exposed to OTEZLA, compared to none in placebo treated patients (0/495). Suicidal ideation and behavior were observed in 0.2% (3/1441) of patients on OTEZLA, compared to none on placebo (0/495). Two patients who received placebo committed suicide compared to none on OTEZLA.
Carefully weigh the risks and benefits of treatment with OTEZLA for patients with a history of depression and/or suicidal thoughts/behavior, or in patients who develop such symptoms while on OTEZLA. Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and they should contact their healthcare provider if such changes occur.
Weight Decrease: Body weight loss of 5-10% was reported in 10% of patients taking OTEZLA and in 3.3% of patients taking placebo. Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of OTEZLA.
Drug Interactions: Apremilast exposure was decreased when OTEZLA was co-administered with rifampin, a strong
Adverse reactions reported in at least 2% of patients taking OTEZLA, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 16 weeks (after the initial 5-day titration), were (OTEZLA%, placebo%): diarrhea (7.7, 1.6); nausea (8.9, 3.1); headache (5.9, 2.2); upper respiratory tract infection (3.9, 1.8); vomiting (3.2, 0.4); nasopharyngitis (2.6, 1.6); upper abdominal pain (2.0, 0.2).
Use in Specific Populations
Pregnancy and Nursing Mothers: OTEZLA is Pregnancy Category C; it has not been studied in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether apremilast or its metabolites are present in human milk. Caution should be exercised when OTEZLA is administered to a nursing woman.
Renal Impairment: OTEZLA dosage should be reduced in patients with severe renal impairment (creatinine clearance less than 30 mL/min); for details, see Dosage and Administration, Section 2, in the Full Prescribing Information.
Please click here for Full Prescribing Information.
Psoriasis is an immune-mediated, non-contagious chronic inflammatory skin disorder of unknown cause. The disorder is a chronic recurring condition which varies in severity from minor localized patches to complete body coverage. Plaque psoriasis is the most common type of psoriasis. About 80 percent of people who develop psoriasis have plaque psoriasis, which appears as patches of raised, reddish skin covered by silvery-white scales. These patches, or plaques, frequently form on the elbows, knees, lower back, and scalp. Psoriasis occurs nearly equally in males and females. An estimated 125 million people worldwide have psoriasis. To learn more about the role of PDE4 in inflammatory diseases, go to www.discoverpde4.com.
Celgene International Sàrl, located in Boudry,
OTEZLA® is a registered trademark and LIBERATE™ is a trademark of
This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar expressions. Forward-looking statements are based on management's current plans, estimates, assumptions and projections, and speak only as of the date they are made.
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