A robust safety profile in PsA that is tried through 5 years

The following safety information is related to adult patients with PsA. For JPsA or ERA safety data, please see the Prescribing Information.

PsA safety in pivotal trials through Week 16¹

AEs ≥2% in FUTURE 2²*	COSENTYX^® 300 mg (n=100), %	COSENTYX 150 mg (n=100), %	Placebo (n=98), %
Upper respiratory tract infection	4.0	8.0	7.1
Nasopharyngitis	6.0	4.0	8.2
Headache	7.0	4.0	4.1
Nausea	3.0	4.0	4.1
Diarrhea	2.0	2.0	3.1
Urinary tract infection	2.0	4.0	4.1
Hematuria	2.0	3.0	1.0
Vomiting	2.0	2.0	1.0

Selected AEs in the pivotal PsA program

(FUTURE 1 and 2) (N=1003)^3†

COSENTYX any dose^‡

(n=703), %

Placebo

(n=300), %

Infections

Serious infections

1.3

0.3

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

1.6% ISR, low rate of injection site reactions at Week 16 (n=703).

PsA safety profile through Year 5

Pooled analysis of long-term safety profile demonstrated in 1380 patients across 3 phase 3 trials (FUTURE 1-3)^7,8
- Based on a total of 3800+ PY of exposure⁷

AEs of special interest (COSENTYX any dose, EAIR per 100 PY)^7-9	Year 1 N=1380	Year 2 N=1183	Year 3 N=948	Year 4 N=587	Year 5 N=290
Serious infections^\|\|	2.3	2.4	1.4	2.5	1.7
Malignancy	1.2	1.2	1.1	2.0	0.8
Herpes viral infections	4.0	2.6	1.0	1.5	0.0
Candida infections^¶	2.3	2.1	1.1	0.7	0.0
Major adverse cardiac events^#	0.4	0.6	0.7	0.7	0.0
Crohn’s disease^**	0.08	0.00	0.3	0.0	0.0
Ulcerative colitis^**	0.08	0.09	0.1	0.0	0.0
IBD unclassified^**	0.08	0.00	0.1	0.0	0.0

Background rate: According to a pooled estimate from a meta-analysis across 8 studies and ~31,000 patients with PsA, 3.3% had IBD (95% CI: 1.5%, 7.1%; I²=97%). These studies did not specifically assess COSENTYX.¹⁰

No trend toward increased AE incidence rates of MACE, malignancy, IBD, Candida infection, or herpes infection through 5 years

No warning for suicidal ideation and behavior. COSENTYX PsA trials did not screen out patients with depression or suicidal ideation.

No routine lab monitoring, including liver enzymes, during treatment. Evaluate patients for TB infection prior to initiating treatment.

No required premedication with IV formulation.

How do these considerations change counseling conversations with your patients?

~99.4% had NO immunogenicity over 5 years¹⁴

Neutralizing antibodies developed in approximately 0.6% of patients with PsO and were not associated with loss of efficacy^14§§

Please see Important Safety Information, including CONTRAINDICATIONS.

*AEs listed are those occurring in at least 2% of patients in pooled COSENTYX dose group up to Week 16.²
^†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
^§Rate 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
^||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
^#Rates are for the Novartis MedDRA Query term, which comprises (1) any MI, any CV accident, and (2) all other CV events that are fatal, out of a listing of 2200+ terms.⁷
**Data are displayed to 2 decimals where N>1000 and to 1 decimal if N<1000.
^††All trials used SC administration.
^‡‡Protocol permitted investigator discretion to exclude any individuals with any medical or psychiatric conditions that, in the investigator’s opinion, would preclude the patient from adhering to the protocol or completing the study.^2,11-13
^§§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.

Explore SC dosing >Explore IV dosing >

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

COSENTYX clinical trial end points in PsA

FUTURE 2*
(Two-thirds biologic-naive and one-third anti–TNF-α inadequate responders)²
ACR20 responses at Week 16 (NRI) were^1,2:

57% for COSENTYX 300 mg (n=100) (P<0.0001)
60% for COSENTYX 150 mg (n=100) (P<0.0001)
18% for placebo (n=98)

ACR20 responses at Week 24 (primary end point) (NRI) were^1,2:

54% for COSENTYX 300 mg (n=100) (P<0.0001)
51% for COSENTYX 150 mg (n=100) (P<0.0001)
15% for placebo (n=98)
- 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 24²

MAXIMISE*^†
ASAS20 responses at Week 12 (MI) in biologic-naive patients with PsA were¹⁵:

63% for COSENTYX 300 mg (n=164) (primary end point) (P<0.0001)
66% for COSENTYX 150 mg (n=157) (key secondary end point) (P<0.0001)
31% for placebo (n=164)

*All trials used SC administration.
^†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.¹

Study designs

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.^1,16

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: two-thirds of patients were biologic-naive and one-third were anti–TNF-⍺ inadequate responders.^1,2,17

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

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.¹⁸

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; MI, multiple imputation; NRI, nonresponder imputation; NSAIDs, nonsteroidal anti-inflammatory drugs; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; SAE, serious adverse event; SC, subcutaneous; TNF, tumor necrosis factor; VAS, visual analog scale.

Definitions and references

Definitions

AE, adverse event; CV, cardiovascular; EAIR, exposure-adjusted incidence rate; IBD, inflammatory bowel disease; ISR, injection site reaction; IV, intravenous; MACE, major adverse cardiovascular event; MedDRA, Medical Dictionary for Regulatory Activities; MI, myocardial infarction; PsA, psoriatic arthritis; PsO, plaque psoriasis; PTs, preferred terms; PY, patient-year; SC, subcutaneous; TB, tuberculosis.

References

1. Cosentyx. Prescribing information. Novartis Pharmaceuticals Corp.
2. Data on file. CAIN457F2312 (FUTURE 2): Clinical Study Report. Novartis Pharmaceuticals Corp; October 2014.
3. Data on file. AIN457F Summary of Clinical Efficacy in Psoriatic Arthritis. Novartis Pharmaceuticals Corp; February 2015.
4. Nash P, Mease PJ, McInnes IB, et al; on behalf of the FUTURE 3 study group. Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3). Arthritis Res Ther. 2018;20(1):47.
5. Data on file. CAIN457F3302 (MAXIMISE): 1-Year Clinical Study Report. Novartis Pharmaceuticals Corp; August 2020.
6. Data on file. AIN457F Summary of Clinical Safety Appendix 1. Novartis Pharmaceuticals Corp; February 2015.
7. Deodhar A, Mease PJ, McInnes IB, et al. Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data. Arthritis Res Ther. 2019;21(1):111.
8. Schreiber S, Colombel J-F, Feagan BJ, et al. Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials. Ann Rheum Dis. 2019;78(4):473-479.
9. Data on file. AIN457 Pooled Long-term Safety. Novartis Pharmaceuticals Corp; May 2018.
10. Pittam B, Gupta S, Harrison NL, Robertson S, Hughes DM, Zhao SS. Prevalence of extra-articular manifestations in psoriatic arthritis: a systematic review and meta-analysis. Rheumatology (Oxford). 2020;59(9):2199-2206.
11. Data on file. CAIN457F2306 (FUTURE 1): Clinical Trial Protocol. Novartis Pharmaceuticals Corp; December 2013.
12. Data on file. CAIN457F2318 (FUTURE 3): Clinical Trial Protocol. Novartis Pharmaceuticals Corp; December 2014.
13. Data on file. CAIN457F2342 (FUTURE 5): Clinical Study Report. Interim Analysis-Week 24. Novartis Pharmaceuticals Corp; November 2017.
14. Reich K, Blauvelt A, Armstrong A, et al. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits low immunogenicity in psoriasis patients treated up to 5 years. J Eur Acad Dermatol Venereol. 2019;33(9):1733-1741.
15. Baraliakos X, Gossec L, Pournara E, et al. Secukinumab in patients with psoriatic arthritis and axial manifestations: results from the double-blind, randomised, phase 3 MAXIMISE trial. Ann Rheum Dis. 2021;80(5):582-590.
16. Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329-1339.
17. Data on file. CAIN457F2312 (FUTURE 2): Interim Study Report. Novartis Pharmaceuticals Corp; November 2015.
18. Data on file. CAIN457F3302 (MAXIMISE): Data Analysis Report. Novartis Pharmaceuticals Corp; June 2016.