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Psoriatic Arthritis

Safety

Safety data from Otezla® (apremilast) clinical trials
 
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THE MOST COMMON ADVERSE REACTIONS THROUGH WEEK 161

PALACE 1-3: Adverse reactions reported in ≥2% of patients on Otezla 30 mg twice daily and ≥1% observed in patients on placebo for up to day 112 (week 16)1

 
Placebo
Otezla 30 mg BID
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 (%)
Adverse reaction
Diarrheaa6 (1.2)8 (1.6)46 (9.3)38 (7.7)
Nauseaa7 (1.4)15 (3.1)37 (7.4)44 (8.9)
Headachea9 (1.8)11 (2.2)24 (4.8)29 (5.9)
Upper respiratory tract infectionb3 (0.6)9 (1.8)3 (0.6)19 (3.9)
Vomitinga2 (0.4)2 (0.4)4 (0.8)16 (3.2)
Nasopharyngitisb1 (0.2)8 (1.6)1 (0.2)13 (2.6)
Upper abdominal painb0 (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.

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%

The majority of patients reporting the most common adverse reactions did so within the first 2 weeks, and 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

BID, twice daily; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

THE MOST COMMON ADVERSE REACTIONS THROUGH WEEK 2602

PALACE 1-3: 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 (%)
Weeks >156 to ≤208 (N = 401)
n (%)
Weeks >208 to ≤260 (N = 364)
n (%)
Diarrhea 113 (15.7) 20 (3.8) 12 (2.7) 5 (1.2) 2 (0.5)
Nausea 108 (15.0) 11 (2.1) 10 (2.3) 3 (0.7) 1 (0.3)
Headache 75 (10.4) 17 (3.3) 12 (2.7) 8 (2.0) 2 (0.5)
Upper respiratory tract infection 60 (8.3) 27 (5.2) 24 (5.4) 22 (5.5) 21 (5.8)
Nasopharyngitis 41 (5.7) 31 (6.0) 20 (4.5) 27 (6.7) 24 (6.6)
 

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

 

PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

Discontinuation due to adverse reactions occurred at 7.9% during weeks 0 to ≤52, 2.5% during weeks >52 to ≤104, 1.6% during weeks >104 to ≤156, 2.0% during weeks >156 to ≤208, and 1.4% during weeks >208 to ≤2602

ADVERSE REACTIONS OF SPECIAL INTEREST2

PALACE 1-3: Adverse reactions of special interest2

Exposure-adjusted incidence rate/100 patient-yearsa

 
Placebothrough week 16
(145.0 patient-years)
Otezla 30 mg twice dailythrough week 16
(142.6 patient-years)
Otezla 30 mg twice dailythrough week 260
(2196.7 patient-years)
Major adverse cardiac eventsb
Events0.70.00.3
Malignancies
Hematologic0.00.00.1
Skin (excluding melanoma)2.10.00.3
Solid0.70.70.5
Infections
Non-opportunistic serious1.40.71.1
Opportunistic (systemic)0.00.00.1
New cases of tuberculosis (TB)c0.00.00.0
Reactivation of TB0.00.00.0
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

Major adverse cardiac events (MACE) were defined as TEAEs of acute or fatal myocardial infarction, stroke or fatal stroke, or sudden cardiac death.

c

Patients with a history of active or incompletely treated TB were excluded from the trials. The trials included 32 patients with a medical history of TB (including latent TB and pulmonary TB), or a positive tuberculin test.

PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy; TEAEs, treatment-emergent adverse events.

The adverse reactions of special interest were generally similar through 260 weeks2

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

PALACE 1-3: Selected marked abnormalities in laboratory parameters2

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

Placebo-controlleda
Exposure periodb
Weeks 0 to ≤24 Weeks 0 to ≤24 Weeks 0 to ≤52 Weeks >52 to ≤104 Weeks >104 to ≤156 Weeks >156 to ≤208 Weeks >208 to ≤260
Laboratory parameter 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)
Otezla 30 mg BID
(N = 401)
%, (n/N)
Otezla 30 mg BID
(N = 364)
%, (n/N)
Chemistry
ALT >3x ULN 0.2 (1/492) 1.4 (7/492) 1.3 (9/713) 0.4 (2/518) 0.5 (2/442) 0.2 (1/401) 0.3 (1/363)
AST >3x ULN 0.4 (2/491) 0.4 (2/492) 0.6 (4/713) 0.2 (1/518) 0.7 (3/442) 0.5 (2/401) 0.3 (1/363)
Bilirubin >1.8x ULN 0.0 0.4 (2/492) 0.3 (2/713) 0.4 (2/518) 0.5 (2/442) 0.7 (3/401) 1.1 (4/363)
Creatinine >1.7x ULN 0.2 (1/492) 0.2 (1/492) 0.1 (1/713) 0.0 0.0 0.2 (1/401) 0.3 (1/363)
Cholesterol >7.8 mmol/Lc 2.0 (10/492) 3.5 (17/492) 3.8 (27/713) 2.3 (12/518) 2.9 (13/442) 2.5 (10/401) 2.8 (10/363)
Urate, male >590 μmol/L; female >480 μmol/Ld 2.8 (14/492) 3.5 (17/492) 3.8 (27/713) 3.7 (19/518) 4.3 (19/442) 6.0 (24/401) 3.9 (14/363)
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) 1.2 (5/401) 1.4 (5/362)
Leukocytes <1.5 x 109/L 0.0 0.0 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) 2.5 (10/401) 4.4 (16/362)
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) 0.5 (2/401) 1.1 (4/362)
Platelets <75 x 109/L 0.0 0.0 0.0 0.0 0.2 (1/441) 0.0 0.6 (2/362)
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.

 

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy; ULN, upper limit of normal.

Next: Dosing

References: 1. Otezla [package insert]. Thousand Oaks, CA: Amgen Inc. 2. Data on file, Amgen Inc.

INDICATIONS & IMPORTANT SAFETY INFORMATION

INDICATIONS

Otezla® (apremitast) is indicated for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

Otezla is indicated for the treatment of adult patients with active psoriatic arthritis.

Otezla is indicated for the treatment of adult patients with oral ulcers associated with Behçet’s Disease.

IMPORTANT SAFETY INFORMATION

Contraindications

  • Otezla® (apremilast) is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients In the formulation

Warnings and Precautions

  • Diarrhea, Nausea, and Vomiting: Cases of severe diarrhea, nausea, and vomiting were associated with the use of Otezla. Most events occurred within the first few weeks of treatment In some cases patients were hospitalized. Patients 65 years of age or older and patients taking medications that can lead to volume depletion or hypotension may be at a higher risk of complications from severe diarrhea, nausea, or vomiting. Monitor patients who are more susceptible to complications of diarrhea or vomiting; advise patients to contact their healthcare provider. Consider Otezla dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting
  • Depression: 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
    • Psoriasis: Treatment with Otezla is associated with an increase in depression. During clinical trials, 1.3% (12/920) of patients reported depression compared to 0.4% (2/506) on placebo. Depression was reported as serious in 0.1% (1/1 308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1%(1/1 308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezia attempted suicide; one patient on placebo committed suicide
    • Psoriatic Arthritis: Treatment with Otezla is associated with an increase in depression. During clinical trials, 1.0% (10/998) reported depression or depressed mood compared to 0.8% (4/495) treated with placebo. Suicidal ideation and behavior was observed in 0.2% (3/1 441) of patients on Otezla, compared to none in placebo-treated patients. Depression was reported as serious in 0.2% (3/1 441) of patients exposed to Otezla, compared to none in placebo-treated patients (0/495). Two patients who received placebo committed suicide compared to none on Otezla
    • Behcet’s Disease: Treatment with Otezla is associated with an increase in depression. During the clinical trial, 1% (1/104) reported depression or depressed mood compared to 1%(1/103) treated with placebo. No instances of suicidal ideation or behavior were reported in patients treated with Otezla or treated with placebo
  • Weight Decrease: Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla
    • Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients treated with Otezla and in 5% (1 9/382) of patients treated with placebo. Body weight loss of 10% occurred in 2% (16/784) of patients treated with Otezla compared to 1% (3/382) of patients treated with placebo
    • Psoriatic Arthritis: Body weight loss of 5-10% was reported in 10% (49/497) of patients taking Otezla and in 3.3% (16/495) of patients taking placebo
    • Behçet’s Disease: Body weight loss of >5% was reported in 4.9% (5/103) of patients taking Otezla and ¡n 3.9% (4/102) of patients taking placebo
  • Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rilampin, a strong CYP4SO enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP45O enzyme inducers (e.g., rifampin. phenobarbital, carbamazepine, phenytoin) is not recommended

Adverse Reactions

  • Psoriasis: Adverse reactions reported in ≥5% of patients were (Otezla%, ptacebo%): diarrhea (17, 6), nausea (17, 7), upper respiratory tract infection (9, 6), tension headache (8, 4), and headache (6, 4)
  • Psoriatic Arthritis: Adverse reactions reported in at (east 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 (2M, 0.2)
  • Behçet’s Disease: Adverse reactions reported in 5% of patients taking Otezta, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 12 weeks, were (Otezla%, placebo%): diarrhea (41.3, 20.4); nausea (19.2, 10.7); headache (14.4, 10.7); upper respiratory tract infection (11.5, 4.9); upper abdominal pain (8.7, 1.9); vomiting (8.7, 1.9); back pain (7.7, 5.8); viral upper respiratory tract infection (6.7, 4.9); arthralgia (5.8, 2.9)

Use in Specific Populations

  • Pregnancy: Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss. Consider pregnancy planning and prevention for females of reproductive potential There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Otezla during pregnancy. Information about the registry can be obtained by calling 1-877-311-8972 or visiting https://mothertoaby.org/ongoing-study/otezla/
  • Lactation: There are no data on the presence of apremilast or its metabolites in human milk, the effects of apremilast on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastleeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastled child from Otezla or from the underlying maternal condition
  • Renal Impairment: Otezla dosage should be reduced in patients with severe renal impairment (creatinine clearance less than 30 ml/mm); for details, see Dosage and Administration, Section 2, in the Full Prescribing Information

Please click here for Full Prescribing Information.

INDICATIONS & IMPORTANT SAFETY INFORMATION

INDICATIONS

Otezla® (apremitast) is indicated for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

Otezla is indicated for the treatment of adult patients with active psoriatic arthritis.

Otezla is indicated for the treatment of adult patients with oral ulcers associated with Behçet’s Disease.

IMPORTANT SAFETY INFORMATION

Contraindications

  • Otezla® (apremilast) is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients In the formulation

Warnings and Precautions

  • Diarrhea, Nausea, and Vomiting: Cases of severe diarrhea, nausea, and vomiting were associated with the use of Otezla. Most events occurred within the first few weeks of treatment In some cases patients were hospitalized. Patients 65 years of age or older and patients taking medications that can lead to volume depletion or hypotension may be at a higher risk of complications from severe diarrhea, nausea, or vomiting. Monitor patients who are more susceptible to complications of diarrhea or vomiting; advise patients to contact their healthcare provider. Consider Otezla dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting
  • Depression: 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
    • Psoriasis: Treatment with Otezla is associated with an increase in depression. During clinical trials, 1.3% (12/920) of patients reported depression compared to 0.4% (2/506) on placebo. Depression was reported as serious in 0.1% (1/1 308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1%(1/1 308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezia attempted suicide; one patient on placebo committed suicide
    • Psoriatic Arthritis: Treatment with Otezla is associated with an increase in depression. During clinical trials, 1.0% (10/998) reported depression or depressed mood compared to 0.8% (4/495) treated with placebo. Suicidal ideation and behavior was observed in 0.2% (3/1 441) oF patients on Otezla, compared to none in placebo-treated patients. Depression was reported as serious in 0.2% (3/1 441) of patients exposed to Otezla, compared to none in placebo-treated patients (0/495). Two patients who received placebo committed suicide compared to none on Otezla
    • Behcet’s Disease: Treatment with Otezla is associated with an increase in depression. During the clinical trial, 1% (1/104) reported depression or depressed mood compared to 1%(1/103) treated with placebo. No instances of suicidal ideation or behavior were reported in patients treated with Otezla or treated with placebo
  • Weight Decrease: Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla
    • Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients treated with Otezla and in 5% (1 9/382) of patients treated with placebo. Body weight loss of 10% occurred in 2% (16/784) of patients treated with Otezla compared to 1% (3/382) of patients treated with placebo
    • Psoriatic Arthritis: Body weight loss of 5-10% was reported in 10% (49/497) of patients taking Otezla and in 3.3% (16/495) of patients taking placebo
    • Behçet’s Disease: Body weight loss of >5% was reported in 4.9% (5/103) of patients taking Otezla and ¡n 3.9% (4/102) of patients taking placebo
  • Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rilampin, a strong CYP4SO enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP45O enzyme inducers (e.g., rifampin. phenobarbital, carbamazepine, phenytoin) is not recommended

Adverse Reactions

  • Psoriasis: Adverse reactions reported in ≥5% of patients were (Otezla%, ptacebo%): diarrhea (17, 6), nausea (17, 7), upper respiratory tract infection (9, 6), tension headache (8, 4), and headache (6, 4)
  • Psoriatic Arthritis: Adverse reactions reported in at (east 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 (2M, 0.2)
  • Behçet’s Disease: Adverse reactions reported in 5% of patients taking Otezta, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 12 weeks, were (Otezla%, placebo%): diarrhea (41.3, 20.4); nausea (19.2, 10.7); headache (14.4, 10.7); upper respiratory tract infection (11.5, 4.9); upper abdominal pain (8.7, 1.9); vomiting (8.7, 1.9); back pain (7.7, 5.8); viral upper respiratory tract infection (6.7, 4.9); arthralgia (5.8, 2.9)

Use in Specific Populations

  • Pregnancy: Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of letal loss. Consider pregnancy planning and prevention for females of reproductive potential There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Otezla during pregnancy. Information about the registry can be obtained by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/otezla/
  • Lactation: There are no data on the presence of apremilast or its metabolites in human milk, the effects of apremilast on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastleeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastled child from Otezla or from the underlying maternal condition
  • Renal Impairment: Otezla dosage should be reduced in patients with severe renal impairment (creatinine clearance less than 30 ml/mm); for details, see Dosage and Administration, Section 2, in the Full Prescribing Information

Please click here for Full Prescribing Information.