Efficacy

Results from Otezla^® (apremilast) clinical trials

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ACR20 Response
Joint Tenderness and Swelling
Dactylitis
Enthesitis
Axial Symptoms
Fatigue
Physical Function
PALACE 4: DMARD-naïve
ACTIVE: Biologic-naïve

OTEZLA SIGNIFICANTLY IMPROVED ACR20 RESPONSE, WITH OR WITHOUT DMARDs^1-3

PALACE 1: ACR20 responders at week 16 (primary endpoint)^1,a

Nonresponder imputation; full analysis set

Full analysis set consists of all patients who were randomized as specified in the protocol.

ACR, American College of Rheumatology; BID, twice daily; DMARD, disease-modifying antirheumatic drug; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy

Otezla also significantly improved ACR20 response vs placebo at week 16 in PALACE 2 and 3; nonresponder imputation; intent-to-treat analysis^1,2,4,5
PALACE 2: 32.1% vs 18.9%, Otezla 30 mg BID vs placebo respectively (P<0.05)
PALACE 3: 41% vs 18%, Otezla 30 mg BID vs placebo (P<0.0001)
ACR responses observed in the people treated with Otezla were consistent in the patients who had received either prior small-molecule or prior biologic DMARD use⁴

ACR20 response through 5 years^2,3

Pooled PALACE 1-3: ACR20 responders^2,3,a-c

Secondary endpoint; data as observed

^aIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16 or week 24) through week 260. ^bData presented "as observed" with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^cThe open-label extension (OLE) period was from weeks 52 to 260. ^dn/N, number of responders/number of patients who had sufficient data for a definitive determination of response status at the timepoint, which includes patients who discontinued early between the preceding timepoint and the specific timepoint.

Patients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other)^2,3
Placebo-controlled efficacy data were collected and analyzed through week 24. Placebo nonresponders at week 16 were re-randomized to either Otezla treatment arm. At week 24, all remaining patients were re-randomized to either Otezla treatment arm. Patients treated with Otezla remained on their initial treatment^1-3
Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), 11.9% of patients had adverse events that led to discontinuation from the study^2,c

Next: Joint Tenderness and Swelling

Mean reduction in joint tenderness and swelling through 5 years^1,2

Pooled PALACE 1-3: Mean percent reduction in tender and swollen joints^1,2,a-c

Prespecified analysis; data as observed

CRP, C-reactive protein, HAQ-DI, Health Assessment Questionnaire-Disability Index; LOCF, last observation carried forward; SJC, swollen joint count; TJC, tender joint count.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), 11.9% of patients had adverse events that led to discontinuation from the study^1,c

In PALACE 1, treatment with Otezla also significantly improved all other measured ACR components vs placebo at week 16—pain and global disease activity assessed by patients, global disease activity assessed by physicians, HAQ-DI, and CRP. Consistent results were observed in PALACE 2 and 3.^2,3,*

Data based on results of an LOCF analysis of the FAS population.

Next: Dactylitis

RESOLUTION OF PREEXISTING DACTYLITIS THROUGH 5 YEARS^1,2

Pooled PALACE 1-3: Resolution of dactylitis^1,2,a-d

Secondary endpoint; data as observed

Mean Dactylitis Severity Score at baseline: Otezla 30 mg BID, 3.3; Placebo, 3.4^1,g

^aPatients with preexisting dactylitis. ^bData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^cIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^dThe open-label extension (OLE) period was from weeks 52 to 260. ^eDactylitis severity count = 0-20; a score of 0 indicates resolution of dactylitis. ^fn/N number of responders/number of patients who had sufficient data for a definitive determination of response status at the timepoint, which includes patients who discontinued early between the preceding timepoint and the specific timepoint. ^gIncludes patients re-randomized to receive Otezla 30 mg BID at week 16 or week 24.

DSS, Dactylitis Severity Score.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), 11.9% of patients had adverse events that led to discontinuation from the study^1,d

Next: Enthesitis

RESOLUTION OF PREEXISTING ENTHESITIS THROUGH 5 YEARS^1,2

Pooled PALACE 1-3: Resolution of enthesitis^1,2.a-d

Secondary endpoint; data as observed

Mean MASES at Baseline: Otezla 30 mg BID, 4.5: Placebo 4.6^3,g

^aPatients with preexisting enthesitis. ^bData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^cIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^dThe open-label extension (OLE) period was from weeks 52 to 260. ^eMASES scale = 0-13; a score of 0 indicates resolution of enthesitis. ^fn/N number of responders/number of patients who had sufficient data for a definitive determination of response status at the timepoint, which includes patients who discontinued early between the preceding timepoint and the specific timepoint. ^gIncludes patients re-randomized to receive Otezla 30 mg BID at week 16 or week 24.

MASES, Maastricht Ankylosing Spondylitis Enthesitis Score.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), 11.9% of patients had adverse events that led to discontinuation from the study^1,d

Next: Axial Symptoms

MEAN CHANGE IN AXIAL SYMPTOMS THROUGH 5 YEARS¹

Pooled PALACE 1-3: Mean change in BASDAI^1,a-c

Prespecified exploratory endpoint; data as observed

Pooled analysis of PALACE 1-3 patients considered by investigators to have axial symptoms (baseline BASDAI ≥4), although axial involvement was not confirmed by MRI.²

^aIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^bData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^cThe open-label extension (OLE) period was from weeks 52 to 260. ^dBASDAI is used to clinically assess possible axial involvement in psoriatic arthritis.^3,4 ^eThe final score ranges from 0 to 10, with a lower score denoting less severe axial symptoms.⁵ ^fThe n at each timepoint represents patients with a baseline value and a post-baseline value at the timepoint and includes patients who discontinued early between the preceding timepoint and the specific timepoint.

BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; MRI, magnetic resonance imaging.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), 11.9% of patients had adverse events that led to discontinuation from the study^1,c

Next: Fatigue

MEAN PERCENT CHANGE IN FATIGUE SCORE THROUGH 5 YEARS¹

Pooled PALACE 1-3: Mean percent change in FACIT-Fatigue score^1,a-c

Prespecified secondary endpoint; data as observed

^aData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^bIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^cThe open-label extension (OLE) period was from weeks 52 to 260. ^dFACIT-F is a 13-item, self-administered questionnaire that assesses fatigue and its physical impact on daily activities and function. The total FACIT-F score ranges from 0 to 52 with lower scores denoting higher levels of fatigue.² ^eThe n at each timepoint represents patients with a baseline value and a post-baseline value at the timepoint and includes patients who discontinued early between the preceding timepoint and the specific timepoint.

FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), 11.9% of patients had adverse events that led to discontinuation from the study^1,c

Next: Physical Function

PHYSICAL FUNCTION RESPONSE THROUGH 5 YEARS¹

Pooled PALACE 1-3: Patients achieving HAQ-DI MCID of ≥0.35^2,a-c

Post-hoc analysis; data as observed

^aResults of the post-hoc analysis are exploratory and conclusions cannot be made. ^bData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^cIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^dThe open-label extension (OLE) period was from weeks 52 to 260. ^eHAQ–DI is a 20-item, self-administered questionnaire that assesses a patient’s level of functional ability. The total HAQ–DI score ranges from 0 to 3, with 0 representing normal or no difficulty, and 3 representing inability to perform.¹ ^fn/N number of responders/number of patients who had sufficient data for a definitive determination of response status at the timepoint, which includes patients who discontinued early between the preceding timepoint and the specific timepoint.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), 11.9% of patients had adverse events that led to discontinuation from the study^1,d

Mean change from baseline in HAQ-DI score was significantly improved at week 16 with Otezla 30 mg (-0.244, n=159) vs placebo (-0.086, n=165); P=0.0017 in PALACE 1. Similar results were observed in PALACE 2 and 3^1-4

BID, twice daily; DMARDs, disease-modifying antirheumatic drugs; FAS, full analysis set; HAQ-DI, Health Assessment Questionnaire-Disability Index; LOCF, last observation carried forward; MCID, minimal clinically important difference; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

Next: PALACE 4: DMARD-naïve

Otezla significantly improved ACR20 response in DMARD-naïve patients¹

PALACE 4: ACR20 responders at week 16 (primary endpoint)¹

Nonresponder imputation; full analysis set

ACR, American College of Rheumatology; BID, twice daily; DMARD, disease-modifying antirheumatic drug; PALACE, Psoriatic Arthritis Long-Term Assessment of Clinical Efficacy.

In PALACE 4:

The most common adverse reactions (reported in ≥5% of patients) on Otezla 30 mg BID through week 16 (N=176) included diarrhea (11.4%), nausea (14.3%), and headache (8.0%)¹*
Discontinuations due to any adverse reactions occurred at 5.2% during weeks 0 to ≤52, 3.5% during weeks >52 to ≤104, 3.1% during weeks >104 to ≤156, 0.0% for weeks >156 to ≤208, and 1.5% for weeks >208 to ≤260

Adverse reactions shown are those that occurred in 5% or more of patients receiving Otezla 30 mg BID through week 16, before early escape.

PALACE 4 clinical trial program^1,2

Program:

Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel group study^1,2
527 DMARD-naïve adult patients with active psoriatic arthritis¹
Click here to see full study design for more information

ACR20 RESPONSE THROUGH 5 YEARS^1,2

PALACE 4: ACR20 responders^1,2,a-c

Secondary endpoint; data as observed

^aIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^bData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^cThe open-label extension (OLE) period was from weeks 52 to 260. ^dPatients discontinued treatment during the study due to adverse reactions, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance and other). ^en/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the timepoint, which includes subjects who discontinued early between the preceding timepoint and the specific timepoint.

Placebo-controlled efficacy data were collected and analyzed through week 24. Placebo nonresponders at week 16 were re-randomized to either Otezla arm. At week 24, all remaining patients receiving placebo were re-randomized to either Otezla treatment arm. Patients treated with Otezla remained on their initial treatment. Patients entering a long-term extension phase could be treated through 5 years¹
Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), a total of 18 patients (10.3%) taking Otezla 30 mg BID had adverse events that led to discontinuation from the study^2,c

MEAN REDUCTION IN JOINT TENDERNESS AND SWELLING THROUGH 5 YEARS²

PALACE 4: Mean percent reduction in tender and swollen joints^2,a-c

Prespecified analysis; data as observed

^aIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^bData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^cThe open-label extension (OLE) period was from weeks 52 to 260. ^dPatients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other). ^eThe n at each timepoint represents patients with a baseline value and a post-baseline value at the timepoint and includes subjects who discontinued early between the preceding timepoint and the specific timepoint. ^fData from the mITT population.

mITT, modified intent to treat; SJC, swollen joint count; TJC, tender joint count.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), 11.9% of patients had adverse events that led to discontinuation from the study^2,c

Treatment with Otezla also significantly improved these measured ACR components vs placebo at week 16—pain and global disease activity assessed by patients, global disease activity assessed by physicians, and HAQ–DI^2,*

^*Data from the mITT population.

HAQ–DI, Health Assessment Questionnaire–Disability Index.

RESOLUTION OF PREEXISTING DACTYLITIS THROUGH 5 YEARS²

PALACE 4: Resolution of dactylitis^2,a-f

Secondary endpoint; data as observed

Mean Dactylitis Severity Score at baseline: placebo, 3.1; Otezla 30 mg BID, 3.5²

^aExamined among patients with dactylitis at baseline (n=129). ^bIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^cData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^dThe open-label extension (OLE) period was from weeks 52 to 260. ^ePatients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other). ^fDactylitis Severity Score = 0-20; a score of 0 indicates resolution of dactylitis. ^gn/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the timepoint, which includes subjects who discontinued early between the preceding timepoint and the specific timepoint.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), 11.9% of patients had adverse events that led to discontinuation from the study^2,d

RESOLUTION OF PREEXISTING ENTHESITIS THROUGH 5 YEARS²

PALACE 4: Resolution of enthesitis^2a-d

Secondary endpoint; data as observed

Mean MASES at baseline: Placebo, 3.6; Otezla 30 mg BID, 3.7.

^aPost-baseline values examined among patients with enthesitis at baseline (n=162). ^bIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^cData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^dThe open-label extension (OLE) period was from weeks 52 to 260. ^ePatients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other). ^fMASES scale = 0-13, a score of 0 indicated resolution of enthesitis. ^gn/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the timepoint, which includes subjects who discontinued early between the preceding timepoint and the specific timepoint.

MASES, Maastricht Ankylosing Spondylitis Enthesitis Score.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), a total of 18 patients (10.3%) taking Otezla 30 mg BID had adverse events that led to discontinuation from the study^2,d

PATIENT'S ASSESSMENT OF PAIN THROUGH 5 YEARS²

PALACE 4: Mean change in patient's assessment of pain VAS²

Secondary endpoint; data as observed

^aIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^bData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^cThe open-label extension (OLE) period was from weeks 52 to 260. ^dPatients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other). ^ePain was assessed on a 0-100 mm VAS. ^fMean patientʼs assessment of pain VAS score at baseline for patients receiving Otezla 30 mg BID. ^gThe n at each timepoint represents patients with a baseline value and a post-baseline value at the timepoint and includes subjects who discontinued early between the preceding timepoint and the specific timepoint; patients with a zero value at baseline are excluded from the summary of percent change from baseline.

VAS, visual analog scale.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), a total of 18 patients (10.3%) taking Otezla 30 mg BID had adverse events that led to discontinuation from the study^2,c

PHYSICAL FUNCTION RESPONSE THROUGH 5 YEARS²

PALACE 4: Patients achieving HAQ-DI MCID of ≥0.35^2,a-d

Post-hoc analysis; data as observed

^aResults of the post-hoc analysis are exploratory and conclusions cannot be made. ^bIncludes all patients exposed to Otezla, including during the placebo-controlled period, regardless of when patients started taking Otezla (baseline, week 16, or week 24) through week 260. ^cData are presented “as observed” with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 260 weeks. ^dThe open-label extension (OLE) period was from weeks 52 to 260. ^ePatients discontinued treatment during the study due to adverse events, lack of efficacy, and other (withdrawal by patient, loss of follow-up, protocol violation, noncompliance, and other). ^fHAQ-DI is a 20-item, self-administered questionnaire that assesses a patient's level of functional ability. The total HAQ–DI score ranges from 0 to 3, with 0 representing normal or no difficulty, and 3 representing inability to perform.² ^gn/N number of responders/number of patients who had sufficient data for a definitive determination of response status at the timepoint, which includes patients who discontinued early between the preceding timepoint and the specific timepoint.

Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. During the Otezla exposure period (weeks 0 to 260), 11.9% of patients had adverse events that led to discontinuation from the study^2,d

Next: ACTIVE: Biologic-naïve

Otezla significantly improved ACR20 response in biologic-naïve patients at week 16^1,2

The primary endpoint of ACR20 response at week 16 was significantly greater with Otezla 30 mg BID (38.2%, n=110) vs placebo (20.2%, n=109); P=0.0040
(nonresponder imputation; full analysis set)

ACR, American College of Rheumatology; BID, twice daily.

ACTIVE clinical trial program^1,2

Program:

Phase 3b, multicenter, randomized, double-blind, placebo-controlled, parallel group study
219 adult patients with active psoriatic arthritis
Click here to see full study design for more information

ACR20 RESPONSE THROUGH WEEK 52²

ACTIVE: ACR20 responders^2,a

Secondary endpoint; data as observed

^aData are presented "as observed" with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 52 weeks. ^bIncludes all patients exposed to Otezla from baseline who completed treatment through week 52. ^cAt week 16, patients receiving placebo were eligible to be switched to Otezla; at week 24, all remaining patients receiving placebo were switched to Otezla. Only patients who received ≥1 dose of Otezla were included. ^dn/N, number of responders/number of subjects who had sufficient data for a definitive determination of response status at the timepoint, which includes subjects who discontinued early between the preceding timepoint and the specific timepoint.

ACTIVE, Assessing Apremilast Monotherapy in a Clinical Trial of Biologic-Naïve Patients With Psoriatic Arthritis.

Statistical significance was not reached for the first secondary endpoint. Hierarchical testing was therefore stopped, making the remaining secondary endpoints statistically nonsignificant²

In ACTIVE:

The most common adverse reactions (reported in ≥5% of patients) during the apremilast exposure period (n=206) included diarrhea (16.0%); nausea (7.8%); nasopharyngitis (7.8%); headache (5.8%); hypertension (6.3%); upper respiratory tract infection (6.8%)²
Discontinuations due to any adverse reactions occurred at 8.3% during the apremilast exposure period (n=206)²

JOINT TENDERNESS REDUCTION THROUGH WEEK 52¹

ACTIVE: Mean percent reduction in tender joints^1,a

Exploratory analysis; data as observed

^aData are presented "as observed" with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 52 weeks. ^bIncludes all patients exposed to Otezla from baseline who completed treatment through week 52. ^cAt week 16, patients receiving placebo were eligible to be switched to Otezla; at week 24, all remaining patients receiving placebo were switched to Otezla. Only patients who received ≥1 dose of Otezla were included. ^dThe n at each timepoint represents patients with a baseline value and a post-baseline value at the timepoint and includes subjects who discontinued early between the preceding timepoint and the specific timepoint.

JOINT SWELLING REDUCTION THROUGH WEEK 52²

ACTIVE: Mean percent reduction in swollen joints^1,a

Exploratory analysis; data as observed

^aData are presented "as observed" with no imputation for missing values in order to describe outcomes among those patients who continued to receive treatment over 52 weeks. ^bIncludes all patients exposed to Otezla from baseline who completed treatment through week 52. ^cAt week 16, patients receiving placebo were eligible to be switched to Otezla; at week 24, all remaining patients receiving placebo were switched to Otezla. Only patients who received ≥1 dose of Otezla were included. ^dThe n at each timepoint represents patients with a baseline value and a post-baseline value at the timepoint and includes subjects who discontinued early between the preceding timepoint and the specific timepoint.

Statistical significance was not reached for the first secondary endpoint. Hierarchical testing was therefore stopped, making the remaining secondary endpoints nonsignificant²

Next: Safety

References: 1. Otezla [package insert]. Thousand Oaks, CA: Amgen Inc. 2. Data on file, Amgen Inc. 3. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. J Rheumatol. 2015;42(3):479-488. 4. Cutolo M, Myerson GE, Fleischmann RM, et al. J Rheumatol. 2016;43(9):1724-1734. 5. Edwards CJ, Blanco JC, Crowley J, et al. Ann Rheum Dis. 2016;75(6):1065-1073.

References: 1. Data on file, Amgen Inc. 2. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. J Rheumatol. 2015;42(3):479-488. 3. Otezla [package insert]. Thousand Oaks, CA: Amgen Inc.

References: 1. Data on file, Amgen Inc. 2. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. J Rheumatol. 2015;42(3):479-488.

References: 1. Data on file, Amgen Inc. 2. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. J Rheumatol. 2015;42(3):479-488. 3. Otezla [package insert]. Thousand Oaks, CA: Amgen Inc.

References: 1. Data on file, Amgen Inc. 2. Mease PJ, Marzo-Ortega H, Poder A, et al. Apremilast, an Oral Phosphodiesterase 4 Inhibitor, Is Associated With Long-term (52-Week) Improvements in BASDAI in Patients With Psoriatic Arthritis: Pooled Results From 3 Phase III, Randomized, Controlled Trials. Presented at: the Annual European Congress of Rheumatology EULAR 2016; 8-11 June 2016; London, UK. 3. Fernandez-Sueiro JL, Willisch A, Pertega-Diaz S, et al. Arthritis Care Res. 2010;62(1):78-85. 4. Nash P, Lubrano E, Cauli A, Taylor WJ, Olivieri I, Gladman DD. J Rheumatol. 2014;41(11):2286-2289. 5. Zochling J. Arthritis Care Res. 2011;63(11):S47-S58.

References: 1. Data on file, Amgen Inc. 2. Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Cancer. 2002;94(2):528-538.

References: 1. Data on file, Amgen Inc. 2. Otezla [package insert]. Thousand Oaks, CA: Amgen Inc. 3. Cutolo M, Myerson GE, Fleischmann RM, et al. J Rheumatol. 2016;43(9):1724-1734. 4. Edwards CJ, Blanco JC, Crowley J, et al. Ann Rheum Dis. 2016;75(6):1065-1073.

References: 1. Wells AF, Edwards CJ, Kivitz AJ, et al. Rheumatology (Oxford). 2018;57(7):1253-1263. 2. Data on file, Amgen Inc.

References: 1. Nash P, Ohson K, Walsh J, et al. Ann Rheum Dis. doi:10.1136/annrheumdis-2017-211568. 2. Data on file, Amgen Inc.

INDICATIONS & IMPORTANT SAFETY INFORMATION

INDICATIONS

Otezla^® (apremilast) is indicated for the treatment of adult 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% (1/1308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1% (1/1308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezla 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% (3/1441) of patients on Otezla, compared to none in placebo-treated patients. Depression was reported as serious in 0.2% (3/1441) 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
Behçet’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% (19/382) 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 in 3.9% (4/102) of patients taking placebo

Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rifampin, a strong CYP450 enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended

Adverse Reactions

Psoriasis: Adverse reactions reported in ≥5% of patients were (Otezla%, placebo%): 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 least 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 (2.0, 0.2)
Behçet’s Disease: Adverse reactions reported in ≥5% of patients taking Otezla, 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://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 breastfeeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastfed 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/min); 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^® (apremilast) is indicated for the treatment of adult 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% (1/1308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1%(1/1308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezla 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% (3/1441) of patients on Otezla, compared to none in placebo-treated patients. Depression was reported as serious in 0.2% (3/1441) 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
Behçet’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% (19/382) 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 in 3.9% (4/102) of patients taking placebo

Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rifampin, a strong CYP450 enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended

Adverse Reactions

Psoriasis: Adverse reactions reported in ≥5% of patients were (Otezla%, placebo%): 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 least 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 (2.0, 0.2)
Behçet’s Disease: Adverse reactions reported in ≥5% of patients taking Otezla, 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://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 breastfeeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastfed 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/min); for details, see Dosage and Administration, Section 2, in the Full Prescribing Information

Please click here for Full Prescribing Information.

The FDA approves new data for otezla® (apremilast)

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Efficacy

OTEZLA SIGNIFICANTLY IMPROVED ACR20 RESPONSE, WITH OR WITHOUT DMARDs1-3

PALACE 1: ACR20 responders at week 16 (primary endpoint)1,a

ACR20 response through 5 years2,3

Pooled PALACE 1-3: ACR20 responders2,3,a-c

Mean reduction in joint tenderness and swelling through 5 years1,2

Pooled PALACE 1-3: Mean percent reduction in tender and swollen joints1,2,a-c

In PALACE 1, treatment with Otezla also significantly improved all other measured ACR components vs placebo at week 16—pain and global disease activity assessed by patients, global disease activity assessed by physicians, HAQ-DI, and CRP. Consistent results were observed in PALACE 2 and 3.2,3,*

RESOLUTION OF PREEXISTING DACTYLITIS THROUGH 5 YEARS1,2

Pooled PALACE 1-3: Resolution of dactylitis1,2,a-d

RESOLUTION OF PREEXISTING ENTHESITIS THROUGH 5 YEARS1,2

Pooled PALACE 1-3: Resolution of enthesitis1,2.a-d

MEAN CHANGE IN AXIAL SYMPTOMS THROUGH 5 YEARS1

Pooled PALACE 1-3: Mean change in BASDAI1,a-c

Pooled analysis of PALACE 1-3 patients considered by investigators to have axial symptoms (baseline BASDAI ≥4), although axial involvement was not confirmed by MRI.2

MEAN PERCENT CHANGE IN FATIGUE SCORE THROUGH 5 YEARS1

Pooled PALACE 1-3: Mean percent change in FACIT-Fatigue score1,a-c

PHYSICAL FUNCTION RESPONSE THROUGH 5 YEARS1

Pooled PALACE 1-3: Patients achieving HAQ-DI MCID of ≥0.352,a-c

Mean change from baseline in HAQ-DI score was significantly improved at week 16 with Otezla 30 mg (-0.244, n=159) vs placebo (-0.086, n=165); P=0.0017 in PALACE 1. Similar results were observed in PALACE 2 and 31-4

Otezla significantly improved ACR20 response in DMARD-naïve patients1

PALACE 4: ACR20 responders at week 16 (primary endpoint)1

PALACE 4 clinical trial program1,2

Program:

ACR20 RESPONSE THROUGH 5 YEARS1,2

PALACE 4: ACR20 responders1,2,a-c

MEAN REDUCTION IN JOINT TENDERNESS AND SWELLING THROUGH 5 YEARS2

PALACE 4: Mean percent reduction in tender and swollen joints2,a-c

Treatment with Otezla also significantly improved these measured ACR components vs placebo at week 16—pain and global disease activity assessed by patients, global disease activity assessed by physicians, and HAQ–DI2,*

RESOLUTION OF PREEXISTING DACTYLITIS THROUGH 5 YEARS2

PALACE 4: Resolution of dactylitis2,a-f

Mean Dactylitis Severity Score at baseline: placebo, 3.1; Otezla 30 mg BID, 3.52

RESOLUTION OF PREEXISTING ENTHESITIS THROUGH 5 YEARS2

PALACE 4: Resolution of enthesitis2a-d

Mean MASES at baseline: Placebo, 3.6; Otezla 30 mg BID, 3.7.

PATIENT'S ASSESSMENT OF PAIN THROUGH 5 YEARS2

PALACE 4: Mean change in patient's assessment of pain VAS2

PHYSICAL FUNCTION RESPONSE THROUGH 5 YEARS2

PALACE 4: Patients achieving HAQ-DI MCID of ≥0.352,a-d

Otezla significantly improved ACR20 response in biologic-naïve patients at week 161,2

The primary endpoint of ACR20 response at week 16 was significantly greater with Otezla 30 mg BID (38.2%, n=110) vs placebo (20.2%, n=109); P=0.0040 (nonresponder imputation; full analysis set)

ACTIVE clinical trial program1,2

Program:

ACR20 RESPONSE THROUGH WEEK 522

ACTIVE: ACR20 responders2,a

JOINT TENDERNESS REDUCTION THROUGH WEEK 521

ACTIVE: Mean percent reduction in tender joints1,a

JOINT SWELLING REDUCTION THROUGH WEEK 522

ACTIVE: Mean percent reduction in swollen joints1,a

INDICATIONS & IMPORTANT SAFETY INFORMATION

INDICATIONS

IMPORTANT SAFETY INFORMATION

INDICATIONS & IMPORTANT SAFETY INFORMATION

INDICATIONS

IMPORTANT SAFETY INFORMATION

The FDA approves new data
for otezla^® (apremilast)

OTEZLA SIGNIFICANTLY IMPROVED ACR20 RESPONSE, WITH OR WITHOUT DMARDs^1-3

PALACE 1: ACR20 responders at week 16 (primary endpoint)^1,a

ACR20 response through 5 years^2,3

Pooled PALACE 1-3: ACR20 responders^2,3,a-c

Mean reduction in joint tenderness and swelling through 5 years^1,2

Pooled PALACE 1-3: Mean percent reduction in tender and swollen joints^1,2,a-c

In PALACE 1, treatment with Otezla also significantly improved all other measured ACR components vs placebo at week 16—pain and global disease activity assessed by patients, global disease activity assessed by physicians, HAQ-DI, and CRP. Consistent results were observed in PALACE 2 and 3.^2,3,*

RESOLUTION OF PREEXISTING DACTYLITIS THROUGH 5 YEARS^1,2

Pooled PALACE 1-3: Resolution of dactylitis^1,2,a-d

RESOLUTION OF PREEXISTING ENTHESITIS THROUGH 5 YEARS^1,2

Pooled PALACE 1-3: Resolution of enthesitis^1,2.a-d

MEAN CHANGE IN AXIAL SYMPTOMS THROUGH 5 YEARS¹

Pooled PALACE 1-3: Mean change in BASDAI^1,a-c

Pooled analysis of PALACE 1-3 patients considered by investigators to have axial symptoms (baseline BASDAI ≥4), although axial involvement was not confirmed by MRI.²

MEAN PERCENT CHANGE IN FATIGUE SCORE THROUGH 5 YEARS¹

Pooled PALACE 1-3: Mean percent change in FACIT-Fatigue score^1,a-c

PHYSICAL FUNCTION RESPONSE THROUGH 5 YEARS¹

Pooled PALACE 1-3: Patients achieving HAQ-DI MCID of ≥0.35^2,a-c

Mean change from baseline in HAQ-DI score was significantly improved at week 16 with Otezla 30 mg (-0.244, n=159) vs placebo (-0.086, n=165); P=0.0017 in PALACE 1. Similar results were observed in PALACE 2 and 3^1-4

Otezla significantly improved ACR20 response in DMARD-naïve patients¹

PALACE 4: ACR20 responders at week 16 (primary endpoint)¹

PALACE 4 clinical trial program^1,2

ACR20 RESPONSE THROUGH 5 YEARS^1,2

PALACE 4: ACR20 responders^1,2,a-c

MEAN REDUCTION IN JOINT TENDERNESS AND SWELLING THROUGH 5 YEARS²

PALACE 4: Mean percent reduction in tender and swollen joints^2,a-c

Treatment with Otezla also significantly improved these measured ACR components vs placebo at week 16—pain and global disease activity assessed by patients, global disease activity assessed by physicians, and HAQ–DI^2,*

RESOLUTION OF PREEXISTING DACTYLITIS THROUGH 5 YEARS²

PALACE 4: Resolution of dactylitis^2,a-f

Mean Dactylitis Severity Score at baseline: placebo, 3.1; Otezla 30 mg BID, 3.5²

RESOLUTION OF PREEXISTING ENTHESITIS THROUGH 5 YEARS²

PALACE 4: Resolution of enthesitis^2a-d

PATIENT'S ASSESSMENT OF PAIN THROUGH 5 YEARS²

PALACE 4: Mean change in patient's assessment of pain VAS²

PHYSICAL FUNCTION RESPONSE THROUGH 5 YEARS²

PALACE 4: Patients achieving HAQ-DI MCID of ≥0.35^2,a-d

Otezla significantly improved ACR20 response in biologic-naïve patients at week 16^1,2

The primary endpoint of ACR20 response at week 16 was significantly greater with Otezla 30 mg BID (38.2%, n=110) vs placebo (20.2%, n=109); P=0.0040
(nonresponder imputation; full analysis set)

ACTIVE clinical trial program^1,2

ACR20 RESPONSE THROUGH WEEK 52²

ACTIVE: ACR20 responders^2,a

JOINT TENDERNESS REDUCTION THROUGH WEEK 52¹

ACTIVE: Mean percent reduction in tender joints^1,a

JOINT SWELLING REDUCTION THROUGH WEEK 52²

ACTIVE: Mean percent reduction in swollen joints^1,a