Review the Safety Data of Otezla® (apremilast) in Treatment of Psoriatic Arthritis

PALACE: the most common adverse reactions with Otezla through week 16¹

Adverse reactions reported in ≥2% of patients on Otezla 30 mg twice daily and ≥1% than that observed in patients on placebo for up to day 112 (week 16)¹

Adverse Reaction	Placebo		Otezla 30 mg BID
Adverse Reaction	Day 1 to Day 5 (N = 495) n (%)	Day 6 to Day 112 (N = 490) n (%)	Day 1 to Day 5 (N = 497) n (%)	Day 6 to Day 112 (N = 493) n (%)
Diarrhea^a	6 (1.2)	8 (1.6)	46 (9.3)	38 (7.7)
Nausea^a	7 (1.4)	15 (3.1)	37 (7.4)	44 (8.9)
Headache^a	9 (1.8)	11 (2.2)	24 (4.8)	29 (5.9)
Upper respiratory tract infection^b	3 (0.6)	9 (1.8)	3 (0.6)	19 (3.9)
Vomiting^a	2 (0.4)	2 (0.4)	4 (0.8)	16 (3.2)
Nasopharyngitis^b	1 (0.2)	8 (1.6)	1 (0.2)	13 (2.6)
Abdominal pain upper^b	0 (0.0)	1 (0.2)	3 (0.6)	10 (2.0)

a

Of the reported gastrointestinal adverse reactions, 1 patient experienced a serious adverse reaction of nausea and vomiting in Otezla 30 mg twice daily; 1 patient treated with Otezla 20 mg twice daily experienced a serious adverse reaction of diarrhea; 1 patient treated with Otezla 30 mg twice daily experienced a serious adverse reaction of headache.

b

Of the reported adverse drug reactions, none were serious.

The majority of patients reporting nausea and diarrhea did so within the first 2 weeks; the events tended to resolve over time with continued dosing¹

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 reactions in the 3 trials¹

Most common adverse reactions leading to discontinuation: nausea (1.8%), diarrhea (1.8%), and headache (1.2%)
Otezla arm 4.6%; placebo arm 1.2%

PALACE: the most common adverse reactions through week 156²

Adverse reactions in ≥5% of patients on Otezla 30 mg twice daily, any
treatment group²

	Otezla 30 mg twice daily
	Weeks 0 to ≤52 (N = 721) n (%)	Weeks >52 to ≤104 (N = 520) n (%)	Weeks >104 to ≤156 (N = 443) n (%)
Diarrhea	112 (15.5)	20 (3.8)	11 (2.5)
Nausea	108 (15.0)	11 (2.1)	10 (2.3)
Upper respiratory tract infection	60 (8.3)	27 (5.2)	23 (5.2)
Headache	75 (10.4)	17 (3.3)	12 (2.7)
Nasopharyngitis	41 (5.7)	31 (6.0)	19 (4.3)

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

Discontinuation due to adverse reactions occurred at 7.5% during weeks 0 to ≤52, 2.4% during weeks >52 to ≤104, and 1.6% during weeks >104 to ≤156

PALACE: adverse reactions of special interest²

	Exposure-adjusted incidence rate/ 100 patient-years^a
	Placebo (168.2 patient-years)	Otezla 30 mg BID (769.0 patient-years)
Major adverse cardiac events
Events	0.0	0.1
Malignancies
Hematologic	0.0	0.0
Skin (excluding melanoma)	1.2	0.5
Solid (including melanoma)	0.6	0.1
Infections
Non-opportunistic serious	0.6	0.5
Opportunistic (systemic)	0.6	0.0
New cases of tuberculosis (TB)^b	0.0	0.0
Reactivation of TB	0.0	0.0

a

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).

b

Patients with a history of active or incompletely treated TB were excluded from the trials. The trials included 32 patients with a history of fully treated TB, a positive PPD or QuantiFERON^®, or a history of receiving preventive medication for TB.

The adverse reactions of special interest were generally similar through 156 weeks

PALACE: laboratory abnormalities reported in the placebo-controlled period and long-term exposure period in patients on Otezla 30 mg twice daily²

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

Selected marked abnormalities in laboratory parameters²

Laboratory parameter	Placebo-controlled^a		Exposure Period^b
	Weeks 0 to ≤24	Weeks 0 to ≤24	Weeks 0 to ≤52	Weeks >52 to ≤104	Weeks >104 to ≤156
	Placebo (N = 495) %, (n/N)	Otezla 30 mg BID (N = 497) %, (n/N)	Otezla 30 mg BID (N = 721) %, (n/N)	Otezla 30 mg BID (N = 520) %, (n/N)	Otezla 30 mg BID (N = 443) %, (n/N)
Chemistry
AST >3x ULN	0.2 (1/492)	1.4 (7/492)	1.3 (9/713)	0.4 (2/518)	0.5 (2/442)
AST >3x ULN	0.4 (2/491)	0.4 (2/492)	0.6 (4/713)	0.2 (1/518)	0.7 (3/442)
Bilirubin >1.8x ULN	0.0	0.4 (2/492)	0.3 (2/713)	0.4 (2/518)	0.5 (2/442)
Creatinine >1.7x ULN	0.2 (1/492)	0.2 (1/492)	0.1 (1/713)	0.0	0.0
Cholesterol >7.8 mmol/L^c	2.0 (10/492)	3.5 (17/492)	3.8 (27/713)	2.3 (12/518)	2.9 (13/442)
Urate, male >590 μmol/L; female >480 μmol/L^d	2.8 (14/492)	3.5 (17/492)	3.8 (27/713)	3.7 (19/518)	4.3 (19/442)
Hematology
Hemoglobin, male <10.5 g/dL; female <8.5 g/dL	0.2 (1/489)	0.4 (2/489)	0.7 (5/713)	0.8 (4/517)	1.1 (5/442)
Leukocytes <1.5 x 10⁹/L	0.0	0.0	0.0	0.0	0.0
Lymphocytes <0.8 x 10⁹/L	3.5 (17/488)	3.3 (16/489)	3.9 (28/713)	2.9 (15/517)	3.2 (14/442)
Neutrophils <1.0 x 10⁹/L	0.4 (2/488)	0.2 (1/489)	0.3 (2/713)	0.6 (3/517)	0.5 (2/442)
Platelets <75 x 10⁹/L	0.0	0.0	0.0	0.0	0.2 (1/441)

a

Placebo-controlled period includes all data through week 16 for patients initially assigned to placebo who escaped, and all data through week 24 for all other patients.

b

Otezla-exposure period includes all Otezla-exposure data, regardless of when the Otezla exposure started (week 0, 16, or 24).

c

Did not have to be drawn when the patient was fasting.

d

Urate, male >9.9 mg/dL; female >8.1 mg/dL.

Safety

PALACE: the most common adverse reactions with Otezla through week 16¹

Adverse reactions reported in ≥2% of patients on Otezla 30 mg twice daily and ≥1% than that observed in patients on placebo for up to day 112 (week 16)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 dosing¹

Discontinuation rates due to adverse reactions in the 3 trials¹

PALACE: the most common adverse reactions through week 156²

Adverse reactions in ≥5% of patients on Otezla 30 mg twice daily, any
treatment group²

PALACE: adverse reactions of special interest²

The adverse reactions of special interest were generally similar through 156 weeks

PALACE: laboratory abnormalities reported in the placebo-controlled period and long-term exposure period in patients on Otezla 30 mg twice daily²

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

Selected marked abnormalities in laboratory parameters²

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Safety

PALACE: the most common adverse reactions with Otezla through week 161

Adverse reactions reported in ≥2% of patients on Otezla 30 mg twice daily and ≥1% than that observed in patients on placebo for up to day 112 (week 16)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 dosing1

Discontinuation rates due to adverse reactions in the 3 trials1

PALACE: the most common adverse reactions through week 1562

Adverse reactions in ≥5% of patients on Otezla 30 mg twice daily, any treatment group2

PALACE: adverse reactions of special interest2

The adverse reactions of special interest were generally similar through 156 weeks

PALACE: laboratory abnormalities reported in the placebo-controlled period and long-term exposure period in patients on Otezla 30 mg twice daily2

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

Selected marked abnormalities in laboratory parameters2

You are leaving the Otezla® (apremilast) website

Are You aHealthcare Professional?

PALACE: the most common adverse reactions with Otezla through week 16¹

Adverse reactions reported in ≥2% of patients on Otezla 30 mg twice daily and ≥1% than that observed in patients on placebo for up to day 112 (week 16)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 dosing¹

Discontinuation rates due to adverse reactions in the 3 trials¹

PALACE: the most common adverse reactions through week 156²

Adverse reactions in ≥5% of patients on Otezla 30 mg twice daily, any
treatment group²

PALACE: adverse reactions of special interest²

PALACE: laboratory abnormalities reported in the placebo-controlled period and long-term exposure period in patients on Otezla 30 mg twice daily²

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

Selected marked abnormalities in laboratory parameters²

You are leaving the Otezla^® (apremilast) website

Are You a
Healthcare Professional?