Review the Safety of Otezla® (apremilast) in Treatment of Plaque Psoriasis

Adverse reactions

Adverse reactions reported in ≥1% of patients on Otezla and with greater frequency than in subjects on placebo; up to day 112 (week 16)^1,a

	Placebo (n = 506) n (%)	Otezla 30 mg BID (n = 920) n (%)
Diarrhea	32 (6)	160 (17)
Nausea	35 (7)	155 (17)
Upper respiratory tract infection	31 (6)	84 (9)
Tension headache	21 (4)	75 (8)
Headache	19 (4)	55 (6)
Abdominal pain^b	11 (2)	39 (4)
Vomiting	8 (2)	35 (4)
Fatigue	9 (2)	29 (3)
Dyspepsia	6 (1)	29 (3)
Decrease appetite	5 (1)	26 (3)
Insomnia	4 (1)	21 (2)
Back pain	4 (1)	20 (2)
Migraine	5 (1)	19 (2)
Frequent bowel movements	1 (0)	17 (2)
Depression	2 (0)	12 (1)
Bronchitis	2 (0)	12 (1)
Tooth abcess	0 (0)	10 (1)
Folliculitis	0 (0)	9 (1)
Sinus headache	0 (0)	9 (1)

a

The safety of Otezla was assessed in 1426 subjects in 3 randomized, double-blind, placebo-controlled trials (including the ESTEEM studies).

b

Two subjects treated with Otezla experienced serious adverse reaction of abdominal pain.

The long-term safety profile of Otezla through 3 years was generally similar to that observed with Otezla through 16 weeks²

The majority of patients reporting nausea and diarrhea did so within the first 2 weeks; the events tended to resolve over time with continued dosing²

Postmarketing reports of severe diarrhea, nausea, and vomiting have been associated with the use of Otezla. In some cases patients were hospitalized. Monitor patients who are more susceptible to complications of diarrhea or vomiting¹

Discontinuation rates due to adverse reactions¹

Discontinuation of treatment due to any adverse reaction was 6.1% for patients taking Otezla and 4.1% for placebo
The most common adverse reactions leading to discontinuation for patients taking Otezla were nausea (1.6%), diarrhea (1.0%), headache (0.8%)

ESTEEM: Adverse reactions of special interest^2,a

	Exposure-adjusted incidence rate/100 patient-years^b
	Placebo (n = 418)	Otezla 30 mg BID (n = 1184)
Major adverse cardiac events
Events	0.9	0.5
Malignancies
Hematologic	0.0	0.0
Skin (excluding melanoma)	0.9	1.1
Skin (including melanoma)	0.9	0.4
Infections
Non-opportunistic serious	1.7	1.0
Opportunistic	0.0	0.0
Reactivation of tuberculosis (TB)^c	0.0	0.0

In the pooled safety data for the phase 3 studies, 2 patients reported positive QuantiFERON^®-TB Gold test results; both were in ESTEEM 1. Both patient cases were sent for adjudication. One was adjudicated as latent TB; it is unknown whether the patient had latent TB prior to study enrollment. Both patients were treated prophylactically with TB therapy.

a

The placebo group includes data from weeks 0 to 16. For the Otezla group, all data for subjects exposed to Otezla are included regardless of when the Otezla exposure started.

b

Exposure-adjusted incidence rate/100 patient-years is 100 times the number (n) of patients reporting the event divided by patient-years (up to the ﬁrst event start date for patients reporting the event).

c

Patients with a history of active or incompletely treated TB were excluded from the trials. There was no requirement for latent TB screening. The trials included 9 patients with a history of either latent TB, pulmonary TB, disseminated TB, or a positive tuberculin test or QuantiFERON^®-TB Gold.

ESTEEM: Laboratory parameters

The Full Prescribing Information for Otezla has no requirement for routine laboratory monitoring¹

Selected marked abnormalities in laboratory parameters (weeks 0 to 16, pooled placebo-controlled safety population)²

Laboratory parameter	Placebo (n = 418) %	Otezla 30 mg BID (n = 832) %
Chemistry
ALT >3x ULN	0.2	0.1
AST >3x ULN	0.7	0.2
Bilirubin >1.8x ULN	0.2	0.2
Creatinine >1.7x ULN	0.0	0.1
Cholesterol >7.8 mmol/L^a	2.1	0.8
Urate, male >590 µmol/L; female >480 µmol/L	5.0	3.4
Hemoglobin A1c >9%	0.5	0.5
Hematology
Hemoglobin, male <10.5 g/dL; female <8.5 g/dL	0.7	0.2
Lymphocytes <0.8 x 10⁹/L	3.0	1.1
Neutrophils <1.0 x 10⁹/L	0.0	0.0
Platelets >600 x 10⁹/L	0.2	0.0

a

Did not have to be drawn when patient was fasting.

ULN, upper limit of normal.

Safety

Adverse reactions

Adverse reactions reported in ≥1% of patients on Otezla and with greater frequency than in subjects on placebo; up to day 112 (week 16)^1,a

The long-term safety profile of Otezla through 3 years was generally similar to that observed with Otezla through 16 weeks²

The majority of patients reporting nausea and diarrhea did so within the first 2 weeks; the events tended to resolve over time with continued dosing²

Discontinuation rates due to adverse reactions¹

ESTEEM: Adverse reactions of special interest^2,a

ESTEEM: Laboratory parameters

Selected marked abnormalities in laboratory parameters (weeks 0 to 16, pooled placebo-controlled safety population)²

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Safety

Adverse reactions

Adverse reactions reported in ≥1% of patients on Otezla and with greater frequency than in subjects on placebo; up to day 112 (week 16)1,a

The long-term safety profile of Otezla through 3 years was generally similar to that observed with Otezla through 16 weeks2

The majority of patients reporting nausea and diarrhea did so within the first 2 weeks; the events tended to resolve over time with continued dosing2

Discontinuation rates due to adverse reactions1

ESTEEM: Adverse reactions of special interest2,a

ESTEEM: Laboratory parameters

Selected marked abnormalities in laboratory parameters (weeks 0 to 16, pooled placebo-controlled safety population)2

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Adverse reactions reported in ≥1% of patients on Otezla and with greater frequency than in subjects on placebo; up to day 112 (week 16)^1,a

The long-term safety profile of Otezla through 3 years was generally similar to that observed with Otezla through 16 weeks²

The majority of patients reporting nausea and diarrhea did so within the first 2 weeks; the events tended to resolve over time with continued dosing²

Discontinuation rates due to adverse reactions¹

ESTEEM: Adverse reactions of special interest^2,a

Selected marked abnormalities in laboratory parameters (weeks 0 to 16, pooled placebo-controlled safety population)²

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