Safety

Safety data from Otezla^® (apremilast) clinical trials

Click arrow for more information

Adverse Reactions Through Week 16
Adverse Reactions Through Week 208
Additional Safety
Laboratory Parameters

ADVERSE REACTIONS THROUGH WEEK 16¹

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 (%)
Adverse reaction
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)
Decreased 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)

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

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

Discontinuation of treatment due to any adverse reaction was 6.1% for patients taking Otezla and 4.1% for placebo¹
The most common adverse reactions leading to discontinuation for patients taking Otezla were nausea (1.6%), diarrhea (1.0%), headache (0.8%)¹

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

BID, twice daily; ESTEEM, Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis; LIBERATE, Evaluation in a Placebo-Controlled Study of Oral Apremilast and Etanercept in Plaque Psoriasis.

LIBERATE: Adverse reactions through week 16³

LIBERATE: Adverse reactions reported in ≥5%
of patients in any treatment group (weeks 0 to 16)³

	Placebo(n = 84) n (%)	Otezla 30 mg BID (n = 83) n (%)
Adverse reaction
Headache	3 (3.6)	11 (13.3)
Nausea	1 (1.2)	9 (10.8)
Diarrhea	3 (3.6)	9 (10.8)
Upper respiratory tract infection	2 (2.4)	6 (7.2)
Tension headache	4 (4.8)	5 (6.0)
Nasopharyngitis	8 (9.5)	4 (4.8)

Discontinuation of treatment due to adverse reactions was 3.6% for Otezla and 2.4% for placebo³

The long-term safety profile of Otezla was consistent through 2 years of exposure in
patients with moderate to severe plaque psoriasis who continued on Otezla from baseline
within the LIBERATE study²

ESTEEM^®: ADVERSE REACTIONS THROUGH WEEK 208²

Adverse reactions reported in >5% of patients with psoriasis on Otezla
for up to week 208²

	Otezla Exposure Period^2,a
	Weeks 0 to ≤52 Otezla 30 mg BID (n = 1184) n (%)	Weeks >52 to ≤104 Otezla 30 mg BID (n = 653) n (%)	Weeks >104 to ≤156 Otezla 30 mg BID (n = 402) n (%)	Weeks >156 to ≤208 Otezla 30 mg BID (n = 291) n (%)
Adverse reaction
Diarrhea	205 (17.3)	15 (2.3)	7 (1.7)	7 (2.4)
Nausea	186 (15.7)	5 (0.8)	6 (1.5)	3 (1.0)
Upper respiratory tract infection	184 (15.5)	58 (8.9)	28 (7.0)	28 (9.6)
Nasopharyngitis	167 (14.1)	43 (6.6)	24 (6.0)	15 (5.2)
Tension headache	106 (9.0)	8 (1.2)	5 (1.2)	3 (1.0)
Headache	75 (6.3)	6 (0.9)	7 (1.7)	2 (0.7)

Includes all patients in the ESTEEM trials who received Otezla during the time interval relative to the start of Otezla administration.

Discontinuation due to adverse reactions occurred at 7.6% during weeks 0 to ≤52, 3.7% during weeks >52 to ≤104, 3.5% during weeks >104 to ≤156, and 3.8% during weeks >156 to ≤208²
The long-term safety profile of Otezla was consistent through 4 years of exposure in clinical studies of patients with moderate to severe plaque psoriasis²

BID, twice daily; ESTEEM, Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis.

ESTEEM^®: ADVERSE REACTIONS OF SPECIAL INTEREST²

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 (systemic)	0.0	0.0
Reactivation of tuberculosis (TB)^c	0.0	0.0

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.

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).

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.

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.

BID, twice daily; ESTEEM, Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis.

ESTEEM^®: Laboratory parameters²

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

	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 <75 x 10⁹/L	0.0	0.0

Did not have to be drawn when patient was fasting.

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; ESTEEM, Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis; ULN, upper limit of normal.

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

References: 1. Otezla [package insert]. Thousand Oaks, CA: Amgen Inc. 2. Data on file, Amgen Inc. 3. Reich K, Gooderham M, Green L, et al. J Eur Acad Dermatol Venereol. 2017;31(3):507-517. 4. Crowley J, Thaçi D, Joly P, et al. J Am Acad Dermatol. 2017;77(2):310-317. 5. Reich K, Gooderham M, Bewley A, et al. J Eur Acad Dermatol Venereol. 2018;32(3):397-402.

Safety

ADVERSE REACTIONS THROUGH WEEK 16¹

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

LIBERATE: Adverse reactions through week 16³

LIBERATE: Adverse reactions reported in ≥5%
of patients in any treatment group (weeks 0 to 16)³

The long-term safety profile of Otezla was consistent through 2 years of exposure in
patients with moderate to severe plaque psoriasis who continued on Otezla from baseline
within the LIBERATE study²

ESTEEM^®: ADVERSE REACTIONS THROUGH WEEK 208²

Adverse reactions reported in >5% of patients with psoriasis on Otezla
for up to week 208²

ESTEEM^®: ADVERSE REACTIONS OF SPECIAL INTEREST²

Adverse reactions of special interest^2,a

Exposure-adjusted incidence rate/100 patient-years^b

ESTEEM^®: Laboratory parameters²

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

You are leaving the Otezla® (apremilast) website

Are You a Healthcare Professional?

Safety

ADVERSE REACTIONS THROUGH WEEK 161

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

LIBERATE: Adverse reactions through week 163

LIBERATE: Adverse reactions reported in ≥5% of patients in any treatment group (weeks 0 to 16)3

The long-term safety profile of Otezla was consistent through 2 years of exposure in patients with moderate to severe plaque psoriasis who continued on Otezla from baseline within the LIBERATE study2

ESTEEM®: ADVERSE REACTIONS THROUGH WEEK 2082

Adverse reactions reported in >5% of patients with psoriasis on Otezla for up to week 2082

ESTEEM®: ADVERSE REACTIONS OF SPECIAL INTEREST2

Adverse reactions of special interest2,a

Exposure-adjusted incidence rate/100 patient-yearsb

ESTEEM®: Laboratory parameters2

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

You are leaving the Otezla® (apremilast) website

Are You a Healthcare Professional?

ADVERSE REACTIONS THROUGH WEEK 16¹

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

LIBERATE: Adverse reactions through week 16³

LIBERATE: Adverse reactions reported in ≥5%
of patients in any treatment group (weeks 0 to 16)³

The long-term safety profile of Otezla was consistent through 2 years of exposure in
patients with moderate to severe plaque psoriasis who continued on Otezla from baseline
within the LIBERATE study²

ESTEEM^®: ADVERSE REACTIONS THROUGH WEEK 208²

Adverse reactions reported in >5% of patients with psoriasis on Otezla
for up to week 208²

ESTEEM^®: ADVERSE REACTIONS OF SPECIAL INTEREST²

Adverse reactions of special interest^2,a

Exposure-adjusted incidence rate/100 patient-years^b

ESTEEM^®: Laboratory parameters²

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