Psoriatic Arthritis Safety | COSENTYX® (secukinumab)

A robust safety profile in psoriatic arthritis (PsA)

PsA safety in pivotal trials through Week 16¹

Selected Adverse Events in Pivotal PsA Program Through 16 weeks

There were cases of Crohn’s disease and ulcerative colitis that included patients who experienced either exacerbations or the development of new disease. There were 3 cases of inflammatory bowel disease, of which 2 patients received COSENTYX^® and 1 received placebo.¹

If a serious infection develops, discontinue COSENTYX until the infection resolves.¹

If an anaphylactic reaction or other serious allergic reaction occurs, discontinue COSENTYX immediately and initiate appropriate therapy.¹

In FUTURE 3, COSENTYX did not show any new or unexpected safety signals through Week 16.⁴

In MAXIMISE, COSENTYX did not show any new or unexpected safety signals through 1 year.⁵

*AEs listed are those occurring in at least 2% of patients in pooled secukinumab dose group up to Week 16.²

^†Includes 75 mg, 150 mg, and 300 mg doses (pooled outcome).²

^‡Pivotal PsA program was FUTURE 1 and FUTURE 2.³

^§Some patients were IV loaded (10 mg/kg) at Weeks 0, 2, and 4.³

^IIRate of injection site reactions means the percentage of patients affected by 1 or more injection site reaction(s) during the first 16 weeks of the pooled FUTURE 1 and 2 trials.⁶

A robust safety profile that is tried through 5 years

3800+ patient-years of exposure⁷

Pooled analysis of long-term safety profile demonstrated in 1380 patients across 3 phase 3 trials (FUTURE 1-3)^7,8

PsA safety profile through Year 5

Adverse Events of Special Interest Through Year 5

Robust results seen in FUTURE 5 (N=996)^10,11

NO trend toward increased AE incidence rates of MACE, malignancy, or IBD^7-9

NO boxed warning¹

NO required routine lab monitoring during treatment¹

Evaluate patients for TB infection prior to initiating treatment¹

NO known clinically relevant interactions with drugs metabolized by CYP3A4^1‡‡

Results from a drug-drug interaction study in patients with moderate to severe PsO¹

Over 5 years, <1% of patients had immunogenicity¹²

Neutralizing antibodies developed in approximately 0.6% of patients with PsO and were not associated with loss of efficacy^12§§

Please see Important Safety Information, including CONTRAINDICATIONS.

^¶Rates are for the system organ class “infections and infestations,” which includes multiple associated PTs.⁷

^#Rates are for Candida infections high-level term, which includes multiple associated PTs.⁷

**Data are displayed to 2 decimals where N>1000 and to 1 decimal if N<1000.

^††Rates are for the Novartis MedDRA Query term, which comprises (1) any myocardial infarction, any CV accident, and (2) all other CV events that are fatal, out of a listing of 2200+ terms.⁷

^‡‡Upon initiation or discontinuation of COSENTYX in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment of the CYP450 substrate as needed.¹

^§§The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

Please see FUTURE 1, FUTURE 2 (pivotal trial), FUTURE 3, FUTURE 5, and MAXIMISE primary end points and study design details

COSENTYX clinical trial end points

FUTURE 2

FUTURE 2 studied a mixed population of patients with PsA: 2/3 biologic-naive and 1/3 anti–TNF-α inadequate responders²

ACR20 responses at Week 16 (NRI) in the mixed population were 57% (P<0.0001), 60% (P<0.0001), and 18%, respectively, for COSENTYX 300 mg (n=100), 150 mg (n=100), and placebo (n=98)^1,2
The primary end point of ACR20 responses at Week 24 (NRI) was achieved by 54% of patients on COSENTYX 300 mg (n=100) (P<0.0001), 51% on COSENTYX 150 mg (n=100) (P<0.0001), and 15% on placebo (n=98)^1,2
Skin lesions improved in patients with coexistent PsO who received COSENTYX (n=99) compared with placebo (n=43), as measured by the PASI^1,2
Improvements in enthesitis and dactylitis scores were observed in the COSENTYX group compared with placebo at Week 24¹

FUTURE 5

FUTURE 5 studied a mixed population of patients with PsA: more than 2/3 biologic-naive and less than 1/3 anti–TNF-α inadequate responders¹⁰

JOINT¹⁰

ACR20 response rates (NRI) (primary end point) were:

63% for COSENTYX 300 mg (n=222) (P<0.0001)
56% for COSENTYX 150 mg (n=220) (P<0.0001)
27% for placebo (n=332)

ENTHESITIS¹⁰

Complete resolution (LEI=0) in patients with enthesitis at baseline (NRI):

56% for COSENTYX 300 mg (n=140)
55% for COSENTYX 150 mg (n=141)
35% for placebo (n=192)

DACTYLITIS¹⁰

Complete resolution (LDI=0) in patients with dactylitis at baseline (NRI):

66% for COSENTYX 300 mg (n=82)
57% for COSENTYX 150 mg (n=80)
32% for placebo (n=124)

SKIN¹⁰

Patients who achieved PASI 90 (NRI):

54% for COSENTYX 300 mg (n=110)
37% for COSENTYX 150 mg (n=125)
9% for placebo (n=162)

NAIL^10*

Reduction in nail disease (mNAPSI as observed) response rates were^†:

51% for COSENTYX 300 mg (n=125)
53% for COSENTYX 150 mg (n=128)
11% for placebo (n=203)

MAXIMISE

MAXIMISE studied biologic-naive patients with PsA¹³

The primary end point (ASAS20 responses at Week 12) was achieved by 63% of patients on COSENTYX 300 mg (n=164) compared with 31% for placebo (n=164) (MI; P<0.0001)¹³
The key secondary end point, ASAS20 responses at Week 12 in patients on COSENTYX 150 mg, was achieved by 66% (n=157) (MI; P<0.0001)¹³

Data from the MAXIMISE trial, whose study design, patient population, and dosing regimen are consistent with those of FUTURE 2. In FUTURE 2, 20% of patients had spondylitis with peripheral arthritis.

*Nail data in PsA were consistent with those in the dedicated nail PsO study, TRANSFIGURE. Improvement from baseline NAPSI at Week 16 (primary end point) (repeated measures analysis) was 46.1% for COSENTYX 300 mg (n=63) and 11.7% for placebo (n=56) (P<0.0001).^14

†At baseline, mNAPSI scores were 18.0 and 17.8 in the 300 mg and 150 mg arms, respectively. At Week 16, mNAPSI scores were 8.8 and 8.4 in the 300 mg and 150 mg arms, respectively.¹⁰

Study designs

FUTURE 1 study design

FUTURE 1 was a multicenter, randomized, double-blind, placebo-controlled study that evaluated 606 patients with active PsA. Patients were treated with secukinumab 10 mg/kg IV treatment (or placebo) at Weeks 0, 2, and 4, followed by 75 mg or 150 mg subcutaneous COSENTYX treatment (or placebo) every 4 weeks. Patients receiving placebo were rerandomized to receive COSENTYX 75 mg or 150 mg every 4 weeks based on responder status at Week 16 or Week 24. Primary end point was the percentage of patients with ACR20 response at Week 24.^1,15

FUTURE 2 study design

FUTURE 2 was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated 397 adult patients with active PsA (≥3 swollen and ≥3 tender joints) despite use of NSAIDs, corticosteroids, or DMARDs. Patients had a diagnosis for ≥5 years and received subcutaneous COSENTYX 75 mg (n=99), 150 mg (n=100), 300 mg (n=100), or placebo (n=98) at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks thereafter. Patients who received placebo were rerandomized to COSENTYX 150 mg or 300 mg every 4 weeks at Week 16 or Week 24 based on responder status. Primary end point was the percentage of patients with ACR20 response at Week 24. Study population was mixed: 2/3 of patients were biologic-naive and 1/3 were anti–TNF-α inadequate responders.^1,2,16

FUTURE 3 study design

FUTURE 3 was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 3-year study that evaluated 414 adult patients with active PsA. Patients received subcutaneous COSENTYX 150 mg (n=138), 300 mg (n=139), or placebo (n=137) at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks thereafter. At Week 16, patients who received placebo were rerandomized to COSENTYX 150 mg or 300 mg every 4 weeks based on responder status at Week 16 (nonresponders) or Week 24 (responders). Primary end point was the percentage of patients with ACR20 response at Week 24. Autoinjector usability was also examined. Safety assessments included evaluation of AEs, SAEs, and immunogenicity.⁴

FUTURE 5 study design

FUTURE 5 was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial that evaluated 996 adult patients with active PsA. Patients were randomized to receive subcutaneous COSENTYX 150 mg without load (n=222), 150 mg with load (n=220), 300 mg with load (n=222), or placebo (n=332). Patients who received placebo were rerandomized to receive COSENTYX 150 mg or 300 mg every 4 weeks, based on responder status at Week 16 (nonresponders) or Week 24 (responders). Primary end point was the percentage of patients with ACR20 response at Week 16. Secondary end points included change in mTSS at Week 24 from baseline. Study population was mixed: more than 2/3 of patients were biologic-naive and less than 1/3 were anti–TNF-α inadequate responders (individual patients could have been exposed to up to 3 TNF-α inhibitors).^10,17

MAXIMISE study design

MAXIMISE was a randomized, double-blind, placebo-controlled, multicenter, 52-week study that evaluated 498 patients with active PsA and axial skeleton involvement (defined by BASDAI score ≥4, spinal pain VAS ≥40 0 to 100 mm scale) who had inadequate response to at least 2 NSAIDs for at least 4 weeks. Patients were randomized to receive subcutaneous COSENTYX 150 mg (n=165), COSENTYX 300 mg (n=167), or placebo (n=166) at Weeks 0, 1, 2, 3, 4, and 8. Primary end point was the proportion of patients with ASAS20 response at Week 12. After Week 12, patients who were placed in the placebo group at baseline were rerandomized to active treatment with COSENTYX 150 mg or 300 mg, administered every 4 weeks from Week 12 to Week 52 (last dose on Week 48) but remained blinded to dose.¹³

ACR, American College of Rheumatology; AE, adverse event; ASAS, Assessment of SpondyloArthritis international Society criteria; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; DMARDs, disease-modifying antirheumatic drugs; IV, intravenous; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MI, multiple imputation; mNAPSI, modified Nail Psoriasis Severity Index; mTSS, modified Total Sharp Score; NAPSI, Nail Psoriasis Severity Index; NRI, nonresponder imputation; NSAIDs, nonsteroidal anti-inflammatory drugs; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsO, plaque psoriasis; SAE, serious adverse event; TNF, tumor necrosis factor; VAS, visual analog scale.

Tap to see IMPORTANT SAFETY INFORMATION and INDICATIONS

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
COSENTYX^® (secukinumab) is contraindicated in patients with a previous serious hypersensitivity reaction to secukinumab or to any of the excipients in COSENTYX. Cases of anaphylaxis and angioedema have been reported during treatment with COSENTYX...

CONTRAINDICATIONS

COSENTYX^® (secukinumab) is contraindicated in patients with a previous serious hypersensitivity reaction to secukinumab or to any of the excipients in COSENTYX. Cases of anaphylaxis and angioedema have been reported during treatment with COSENTYX.

WARNINGS AND PRECAUTIONS

Infections

COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in COSENTYX treated subjects compared to placebo-treated subjects. In placebo-controlled clinical trials in subjects with moderate to severe PsO, higher rates of common infections, such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%) and mucocutaneous infections with candida (1.2% versus 0.3%) were observed in subjects treated with COSENTYX compared to placebo-treated subjects. A similar increase in risk of infection in subjects treated with COSENTYX was seen in placebo-controlled trials in subjects with PsA, AS and nr-axSpA. The incidence of some types of infections, including fungal infections, appeared to be dose-dependent in clinical trials.

In the postmarketing setting, serious bacterial, viral, and fungal opportunistic infections, and some fatal infections have been reported in patients receiving IL-17 inhibitors including COSENTYX. Cases of Hepatitis B virus reactivation have been reported.

Exercise caution when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, monitor the patient closely and discontinue COSENTYX until the infection resolves.

If signs of Hepatitis B virus reactivation occur, consult a hepatitis specialist. COSENTYX is not recommended for use in patients with active viral hepatitis.

Pre-treatment Evaluation for Tuberculosis

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX. Avoid administration of COSENTYX to patients with active TB infection. Initiate treatment of latent TB prior to administering COSENTYX. Consider anti-TB therapy prior to initiation of COSENTYX in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients closely for signs and symptoms of active TB during and after treatment.

Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD) exacerbations, in some cases serious and/or leading to discontinuation of COSENTYX, occurred in COSENTYX treated subjects during clinical trials in PsO, PsA, AS, nr-axSpA, and HS. In adult subjects with HS, the incidence of IBD was higher in subjects who received COSENTYX 300 mg every 2 weeks (Ulcerative Colitis [UC] 1 case, EAIR 0.2/100 subject-years; Crohn’s Disease [CD] 1 case, EAIR 0.2/100 subject-years) compared to subjects who received COSENTYX 300 mg every 4 weeks (IBD 1 case, EAIR 0.2/100 subject-years). In addition, new onset IBD cases occurred in subjects treated with COSENTYX in clinical trials. In an exploratory trial in 59 subjects with active Crohn’s disease [COSENTYX is not approved for the treatment of Crohn’s disease], there were trends toward greater disease activity and increased adverse reactions in subjects treated with COSENTYX as compared to placebo-treated subjects.

Exercise caution when prescribing COSENTYX to patients with IBD. Patients treated with COSENTYX should be monitored for signs and symptoms of IBD.

Eczematous Eruptions

In postmarketing reports, cases of severe eczematous eruptions, including atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma, were reported in patients receiving COSENTYX; some cases resulted in hospitalization. The onset of eczematous eruptions was variable, ranging from days to months after the first dose of COSENTYX.

Treatment may need to be discontinued to resolve the eczematous eruption. Some patients were successfully treated for eczematous eruptions while continuing COSENTYX.

Hypersensitivity Reactions

Serious hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have been reported in COSENTYX treated subjects in clinical trials and in the post-marketing setting. If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of COSENTYX and initiate appropriate therapy.

The removable caps of the COSENTYX Sensoready^® pen and the COSENTYX 1 mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause an allergic reaction in latex-sensitive individuals. The safe use of the COSENTYX Sensoready pen or prefilled syringe in latex-sensitive individuals has not been studied.

Immunizations

Prior to initiating therapy with COSENTYX, consider completion of all age-appropriate immunizations according to current immunization guidelines. COSENTYX may alter a patient’s immune response to live vaccines. Avoid use of live vaccines in patients treated with COSENTYX.

MOST COMMON ADVERSE REACTIONS

Most common adverse reactions (>1%) are nasopharyngitis, diarrhea, and upper respiratory tract infection.

Please see Full Prescribing Information, including Medication Guide.

10/24 FA-11289065

A robust safety profile in psoriatic arthritis (PsA)

PsA safety in pivotal trials through Week 161

A robust safety profile that is tried through 5 years

3800+ patient-years of exposure7

PsA safety profile through Year 5

Robust results seen in FUTURE 5 (N=996)10,11

NO trend toward increased AE incidence rates of MACE, malignancy, or IBD7-9

NO boxed warning1

NO required routine lab monitoring during treatment1

NO known clinically relevant interactions with drugs metabolized by CYP3A41‡‡

Over 5 years, <1% of patients had immunogenicity12

Robust safety profile over 5 yearsm,n

Robust safety profile overallm

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