Help your patients with PsA achieve remission

As defined by disease activity at 2 years^1-4*

Please see primary end points, study designs, and additional information on clinical trials and real-world studies

In FUTURE 5,^† as observed in biologic-naive patients

~6 of 10 patients achieved MDA at 2 years with Cosentyx 300 mg

150 mg at 2 years: 50% of patients achieved MDA (n=138)¹

40% of biologic-naive patients in the COSENTYX 150-mg arm were up-titrated to 300 mg starting at Week 52, at the investigator’s discretion.¹

In FUTURE 5, MDA was a prespecified exploratory end point at 2 years in a subgroup of biologic-naive patients. No clinical or statistical conclusions can be drawn.⁵

Reaching MDA involves achieving 5 of the following 7 criteria: ≤1 tender joint count; patient global assessment of disease activity VAS (≤20); ≤1 swollen joint count; tender entheseal points ≤1; PASI ≤1 or BSA ≤3%; patient pain VAS ≤15; HAQ-DI ≤0.5.⁵
All patients who met escape criteria (<20% improvement in tender or swollen joint counts) at Week 16 were considered nonresponders at Week 20 and Week 24. Results were analyzed using nonresponder imputation.⁶

*In addition to MDA, PsA disease activity may be assessed using DAS28, which is based on a count of 28 swollen and tender joints, patient global assessment of disease activity VAS, and either ESR or CRP level. A DAS28 score >5.1 implies active disease, ≤3.2 low disease activity, and <2.6 remission. EULAR response criteria are based on DAS28 status in combination with DAS28 improvements.^2,6,7

Up to 4 years of data in a real-world analysis of patients with PsA

77% of patients achieved MDA at Year 4 with COSENTYX (n=104).

Ramonda R et al.: COSENTYX was consistent with the known safety profile. Overall, 4.9% of biologic-naive patients discontinued COSENTYX due to AEs. AEs leading to discontinuation in ≥1% of patients with PsA included ISR (1.8%) and severe recurrent infections (1.3%).⁸

Real-world analyses can only evaluate association, not causation. Efficacy outcomes reported from clinical trials and those collected in a real-world setting are not directly comparable. Clinical trials use prespecified, validated end points, while real-world studies are observational in nature and use data from routine clinical practice. Real-world data may be based on a small sample size and may not reflect outcomes for all patients. Patients are not randomized, and therefore real-world data are not suitable for direct comparison with clinical trial results. The source and type of real-world data may limit the ability to characterize results in relation to end points from clinical trials due to data availability and varying evaluable approaches. While prescribed dosing was consistent with approved labeling, results are pooled across patients prescribed either 300 mg or 150 mg, as determined by their treating rheumatologist.

Clinical trial data

Majority of patients had improvements in physical functioning⁹

In FUTURE 5, as observed in biologic-naive patients⁹

Week 16 (n=149): 67% of patients achieved meaningful HAQ-DI response in the 300 mg group. Year 2 (n=137): 66% of patients achieved meaningful HAQ-DI response in the 300 mg group.

150 mg at Week 16 and Year 2: 58% (n=148) and 66% (n=134) of patients achieved a meaningful HAQ-DI response, respectively (as observed)⁹

In FUTURE 5, HAQ-DI was a prespecified exploratory end point at Week 16 and 2 years in a subgroup of biologic-naive patients. No clinical or statistical conclusions can be drawn.^5,9

The HAQ-DI score is an assessment of a patient’s functional ability to get dressed, get in and out of bed, eat, walk, perform hygiene activities, reach, grip and open doors, and perform daily activities. The HAQ-DI includes 20 questions in 8 categories of functioning.⁶
In FUTURE 5 at Week 16, in a mixed population (secondary end point): least-squares mean change from baseline HAQ-DI score was -0.55 and -0.44 in the COSENTYX 300-mg and 150-mg arms, respectively, and -0.21 in the placebo arm. At baseline, mean HAQ-DI scores were 1.2, 1.3, and 1.3 for the groups receiving COSENTYX 300 mg, 150 mg, and placebo, respectively.⁶

Clinical trial data

Help your patients manage their fatigue

In FUTURE 5, using MMRM analysis in biologic-naive patients¹⁰

Up to 61% improvement in fatigue at 1 year.

At 1 year, patients in the 300-mg arm and the 150-mg arm experienced a 40% and 61% mean change from baseline in FACIT-Fatigue (n=147), respectively¹⁰

In FUTURE 5, fatigue was measured by FACIT-Fatigue, a prespecified exploratory end point at 1 year in a subgroup of biologic-naive patients. No clinical or statistical conclusions can be drawn.^5,10

At 1 year in the mixed population, the FACIT-Fatigue scores were 14.1 and 16.9 for groups receiving COSENTYX 300 mg (n=206) and COSENTYX 150 mg (n=202), respectively.^5,10
At baseline in the mixed population, the FACIT-Fatigue scores were 21.6, 23.6, and 21.7 for groups receiving COSENTYX 300 mg (n=220), COSENTYX 150 mg (n=218), and placebo (n=328), respectively. At Week 16, the FACIT-Fatigue scores were 15.4, 17.1, and 18.8 for groups receiving COSENTYX 300 mg (n=214), COSENTYX 150 mg (n=210), and placebo (n=303), respectively.⁵

The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact on daily activities and function on a scale of 0 (“not at all”) to 4 (“very much”).⁵

^†Trial used SC administration.
^‡58% and 50% of patients achieved MDA at 2 years on COSENTYX 300 mg (n=140) and COSENTYX 150 mg (n=138), respectively (as observed).¹
^§As observed in biologic-naive patients.⁸
^||Defined as a change from baseline HAQ-DI score of ≥0.3.⁵

See PsA safety >

Please see FUTURE 2 (pivotal trial) and FUTURE 5 primary end points or study design details for clinical trials and real-world studies

COSENTYX clinical trial end points in PsA

FUTURE 2*
(Two-thirds biologic-naive and one-third anti–TNF-α inadequate responders)¹¹

ACR20 responses at Week 16 (NRI) were^11,12:

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^11,12:

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^11,12
Improvements in enthesitis and dactylitis scores were observed in the COSENTYX group compared with placebo at Week 24¹¹

FUTURE 5*
(Two-thirds biologic-naive and one-third anti–TNF-α inadequate responders)⁵ 
Results at Week 16⁵

JOINT
FUTURE 5 primary end point
ACR20 response rates (NRI) 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)

ENTHESITIS
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)

DACTYLITIS
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)

SKIN
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^†
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)

Study designs

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.^11-13

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 two-thirds of patients were biologic-naive and less than one-third were anti–TNF-⍺ inadequate responders (individual patients could have been exposed to up to 3 TNF-⍺ inhibitors).^5,6

Real-world data study designs

MDA data are sourced from an analysis by Ramonda R et al., a prospective observational study evaluating a cohort of 685 patients ≥18 years with PsA on COSENTYX for up to 4 years. Data were collected from September 2016 to May 2023 across 15 Italian rheumatology centers. Patients were diagnosed according to CASPAR criteria and started treatment for moderate to severe disease, according to EULAR, GRAPPA, and/or SlR guidelines. Data were limited to patients who persisted with treatment for ≥3 months. A dose of 150 mg or 300 mg was administered subcutaneously for PsO or multidrug failure at Weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter, in accordance with the prescribing information at the discretion of treating rheumatologists. Treatment response was evaluated at 6 and 12 months after the first administration and every year thereafter, up to 4 years.⁸

Real-world data can supplement data from clinical trials^8,15,16

Randomized controlled trials

Real-world studies

Conducted in a highly controlled environment
Prospectively designed with standardized protocol, including prespecified end points
Patient population is prespecified with well-defined inclusion and exclusion criteria, and is randomized to receive active treatment or a comparator
Designed to show causality with high validity due to a controlled environment and used as the standard for FDA approval

Conducted in routine clinical practice
Data are observational
Reflects diverse patient populations who physicians see day-to-day; patients are not randomized
Can only evaluate association and are unable to determine causality
May provide insights on long-term durability of treatment and persistence in clinical practice
Dosing is reflective of what patients received in accordance with approved labeling, but is not necessarily individualized per outcome

*All trials used SC administration.
^†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) (MMRM) 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.⁵

ACR, American College of Rheumatology; CASPAR, Classification Criteria for Psoriatic Arthritis; DMARDs, disease-modifying antirheumatic drugs; EULAR, European Alliance of Associations for Rheumatology; FDA, US Food and Drug Administration; GRAPPA, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MMRM, mixed-effect model repeated measure; 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; SC, subcutaneous; SIR, Italian Society of Rheumatology; TNF, tumor necrosis factor.

Definitions and references

Definitions

AE, adverse event; BSA, body surface area; CRP, C-reactive protein; DAS, disease activity score; ESR, erythrocyte sedimentation rate; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; ISR, injection site reaction; MDA, minimal disease activity; MMRM, mixed-effect model repeated measure; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; SC, subcutaneous; VAS, visual analog scale.

References

1. Data on file. CAIN457F2342 (FUTURE 5): 2-Year Interim Report. Novartis Pharmaceuticals Corp; May 2019.
2. Lubrano E, Perrotta FM. Defining low disease activity states in psoriatic arthritis using novel composite disease instruments. J Rheumatol. 2016;43(9):1765-1766.
3. Gossec L, Kerschbaumer A, Ferreira RJO, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update. Ann Rheum Dis. 2024;83(6):706-719.
4. Coates LC, Soriano ER, Corp N, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021. Nat Rev Rheumatol. 2022;18(8):465-479.
5. Data on file. CAIN457F2342 (FUTURE 5): Clinical Study Report. Interim Analysis-Week 24. Novartis Pharmaceuticals Corp; November 2017.
6. Mease P, van der Heijde D, Landewé R, et al. Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study. Ann Rheum Dis. 2018;77(6):890-897.
7. Wells G, Becker J-C, Teng J, et al. Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis. 2009;68(6):954-960.
8. Ramonda R, Lorenzin M, Chimenti MS, et al. Four-year effectiveness, safety and drug retention rate of secukinumab in psoriatic arthritis: a real-life Italian multicenter cohort. Arthritis Res Ther. 2024;26(1):172.
9. Data on file. CAIN457F2342 (FUTURE 5): 2-Year HAQ-DI biologic-naive data. Novartis Pharmaceuticals Corp; February 2021.
10. Data on file. CAIN457F2342 (FUTURE 5): Interim Data Analysis Report. FACIT-Fatigue data through Week 52. Novartis Pharmaceuticals Corp; April 2019.
11. Data on file. CAIN457F2312 (FUTURE 2): Clinical Study Report. Novartis Pharmaceuticals Corp; October 2014.
12. Cosentyx. Prescribing information. Novartis Pharmaceuticals Corp.
13. Data on file. CAIN457F2312 (FUTURE 2): Interim Study Report. Novartis Pharmaceuticals Corp; November 2015.
14. Data on file. CAIN457A2313 (TRANSFIGURE): Clinical Study Report. Novartis Pharmaceuticals Corp; November 2015.
15. Monti S, Grosso V, Todoerti M, et al. Randomized controlled trials and real-world data: differences and similarities to untangle literature data. Rheumatology (Oxford). 2018;57(suppl 7):vii54-vii58.
16. Stürmer T, Wang T, Golightly YM, Keil A, Lund JL, Jonsson Funk M. Methodological considerations when analysing and interpreting real-world data. Rheumatology (Oxford). 2020;59(1):14-25.

Help your patients with PsA achieve remission

Up to 4 years of data in a real-world analysis of patients with PsA

Majority of patients had improvements in physical functioning⁹

Help your patients manage their fatigue

Please see FUTURE 2 (pivotal trial) and FUTURE 5 primary end points or study design details for clinical trials and real-world studies

Definitions and references

Important Safety Information

Indications

Help your patients with PsA achieve remission

Up to 4 years of data in a real-world analysis of patients with PsA

Majority of patients had improvements in physical functioning9

Help your patients manage their fatigue

Please see FUTURE 2 (pivotal trial) and FUTURE 5 primary end points or study design details for clinical trials and real-world studies

Definitions and references

Majority of patients had improvements in physical functioning⁹