Apremilast significantly improved preexisting scalp, nail, and palmoplantar psoriasis at week 16 in ESTEEM 2
Improvements in pruritus (itching) seen as early as week 2 in analyses of ESTEEM 1 and 2 and maintained through week 32
Improvement in mean
Long-term safety and tolerability profile in ESTEEM 2 was consistent with previously-reported long-term data from apremilast clinical trial program
ESTEEM 2: 32-Week Data in Patients with Nail, Scalp, and Palmoplantar Involvement
An analysis of ESTEEM 2 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 percent treated with apremilast 30 mg twice daily had at least a 50 percent improvement in this symptom at week 16, compared with 19 percent of those treated with placebo (P < 0.0001). After 32 weeks of treatment with apremilast 30 mg twice daily, 55 percent of patients achieved at least a 50 percent improvement.
Of those patients who had moderate to severe psoriasis on their palms and feet at baseline (n=42), 65 percent 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.
ESTEEM 1 and ESTEEM 2: 32-Week Pruritus Data
An analysis of ESTEEM 1 and 2 found that apremilast improved skin discomfort/pain. Patients report that pruritus (itching) 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 < 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.
"Plaque psoriasis can be a very itchy condition. Psoriasis patients
report that itching is a significant problem that can affect all aspects
of their life from sleeping to concentrating," said Gil Yosipovitch, MD,
Chair of Dermatology at
ESTEEM 2: 52-Week Efficacy Data
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 percent improvement in Psoriasis Area
and Severity Index (PASI) at week 32, mean improvements in
Analysis of data from ESTEEM 2 did not identify new or unexpected adverse events (AEs) for patients treated with apremilast, and the rate of AEs did not increase in frequency over time. AEs reported in at least five percent 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 AEs for those treated with apremilast 30 mg twice daily for 52 weeks was approximately seven percent. No clinically meaningful changes in laboratory measurements were identified over the apremilast 52-week exposure period.
Apremilast was approved on
The views expressed and the techniques presented by the speakers at
About ESTEEM 1 and 2
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 percent of all patients had received prior phototherapy and 54 percent 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 percent of patients had a history of psoriatic arthritis.
Apremilast 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 apremilast exerts its therapeutic action in patients with psoriasis or psoriatic arthritis is not well defined.
Apremilast is indicated for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
Apremilast is also indicated for the treatment of adult patients with active psoriatic arthritis.
IMPORTANT SAFETY INFORMATION
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 apremilast is associated with an increase in adverse reactions of depression. During clinical trials, 1.3% (12/920) of patients treated with apremilast reported depression compared to 0.4% (2/506) on placebo; 0.1% (1/1308) of apremilast patients discontinued treatment due to depression compared with none on placebo (0/506). Depression was reported as serious in 0.1% (1/1308) of patients exposed to apremilast, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1% (1/1308) of patients on apremilast, compared to 0.2% (1/506) on placebo. One patient treated with apremilast attempted suicide; one patient on placebo committed suicide.
Carefully weigh the risks and benefits of treatment with apremilast for patients with a history of depression and/or suicidal thoughts/behavior, or in patients who develop such symptoms while on apremilast. 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% occurred in 12% (96/784) of patients treated with apremilast and in 5% (19/382) of patients treated with placebo. Body weight loss of ≥10% occurred in 2% (16/784) of patients treated with apremilast compared to 1% (3/382) of patients treated with placebo. Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of apremilast.
Drug Interactions: Apremilast exposure was decreased when apremilast was
co-administered with rifampin, a strong
Adverse reactions reported in ≥5% of patients were (apremilast%, placebo%): diarrhea (17, 6), nausea (17, 7), upper respiratory tract infection (9, 6), tension headache (8, 4), and headache (6, 4).
Use in Specific Populations
Pregnancy and Nursing Mothers: apremilast 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 apremilast is administered to a nursing woman.
Renal Impairment: apremilast 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. Psoriasis is believed to be most common in Caucasians
and slightly less common in other ethnic groups. Worldwide, psoriasis is
most common in Scandinavia and other parts of northern
Celgene International Sàrl, located in Boudry, in the
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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. We undertake no obligation to
update any forward-looking statement in light of new information or
future events, except as otherwise required by law. Forward-looking
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difficult to predict and are generally beyond our control. Actual
results or outcomes may differ materially from those implied by the
forward-looking statements as a result of the impact of a number of
factors, many of which are discussed in more detail in our Annual Report
on Form 10-K and other reports filed with the
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