In FUTURE 5,* using NRI analysis

ACR20 responses at Week 2 in a mixed population¹¹:

• 31% for COSENTYX 300 mg (n=222)

• 26% for COSENTYX 150 mg (n=220)

• 15% for placebo (n=332)

In FUTURE 5, ACR20 was a prespecified exploratory end point at Week 2. No clinical or statistical conclusions can be drawn.¹¹

ACR50 in biologic-naive patients at Week 24¹¹

150 mg at Week 24: 45% (n=155)¹¹

In FUTURE 5, ACR50 was a prespecified exploratory end point from Week 1 to Week 24
in a subgroup of biologic-naive patients. No clinical or statistical conclusions can be drawn.¹¹

DURABLE joint symptom relief out to 5 years¹²

In FUTURE 2,* as observed in biologic-naive patients

Over 50% of patients achieved ACR50¹²

150 mg at 5 years: ACR20: 77%; ACR50: 44%; ACR70: 29% (n=48).¹²

54% of biologic-naive patients in the COSENTYX 150-mg arm were up-titrated to 300 mg starting at Week 128, at the investigator’s discretion.¹²

In FUTURE 2, ACR20, ACR50, and ACR70 were prespecified exploratory end points at 5 years in a subgroup of biologic-naive patients. No clinical or statistical conclusions can be drawn.¹³

As with other uncontrolled studies, this phase of the FUTURE 2 study has limitations (eg, no placebo comparisons, and patients responding better are more likely to stay in the study over time).

At baseline, n=67 and n=63 were biologic-naive in the 300-mg and 150-mg arms, respectively.¹³

In the mixed population at 5 years: 74% of patients in the 300-mg arm and the 150-mg arm achieved an ACR20 response; 48% of patients in the 300-mg arm and 42% in the 150-mg arm achieved an ACR50 response; 28% of patients in the 300-mg arm and 29% in the 150-mg arm achieved an ACR70 response.¹²

*Trial used SC administration.

ACR, American College of Rheumatology; NRI, nonresponder imputation; SC, subcutaneous.

150 mg at 1 year: 80% and 65% achieved ASAS20 and ASAS40, respectively, as observed (n=141).¹⁴

In MAXIMISE,* ASAS20 and ASAS40 were prespecified exploratory end points at 1 year. No clinical or statistical conclusions can be drawn.¹⁴

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. MAXIMISE primary end point: 63% experienced relief on COSENTYX 300 mg at Week 12 vs 31% with placebo, as measured by ASAS20 (P<0.0001) (n=164) (MI).^1,6

Hear what your colleagues are saying about this myth in rheumatology

Dr Elizabeth Perkins discusses the use of ASAS and BASDAI when assessing axial PsA.

*Trial used SC administration.

ASAS, Ankylosing SpondyloArthritis International Society criteria; BASDAI, Bath Ankylosing Spondylitis Activity Index; IL-23i, interleukin-23 inhibitor; JAKi, Janus kinase inhibitor; MI, multiple imputation; PsA, psoriatic arthritis; SC, subcutaneous.

In FUTURE 5,* as observed in biologic-naive patients

150 mg at 2 years: 82% achieved complete resolution of enthesitis (n=85)²

Among patients with enthesitis, 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.²   

Complete resolution at Week 16 in a mixed population (prespecified secondary end point) using NRI analysis: 56% for COSENTYX 300 mg (n=140), 55% for COSENTYX 150 mg (n=141) vs 35% for placebo (n=192).¹⁵

In FUTURE 5, complete resolution of enthesitis was a prespecified exploratory end point in a subgroup of biologic-naive patients with LEI >0 at baseline at 2 years. No clinical or statistical conclusions can be drawn.¹¹

As with other uncontrolled studies, this phase of the FUTURE 5 study has limitations (eg, no placebo comparisons, and patients responding better are more likely to stay in the study over time).

At baseline, 97 patients and 93 patients in FUTURE 5 had enthesitis in the 300-mg and 150-mg arms, respectively (biologic-naive).¹¹

*Trial used SC administration.
^†Patients with no enthesitis are defined as having an LEI score of 0 among patients with a score of 1 or more at baseline.¹¹

LEI, Leeds Enthesitis Index; NRI, nonresponder imputation; SC, subcutaneous.

In FUTURE 5,* as observed in biologic-naive patients

150 mg at 2 years: 86% achieved complete resolution of dactylitis (n=43)²

Among patients with dactylitis, 56% 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.²

Complete resolution at Week 16 in a mixed population (secondary end point) using NRI analysis: 66% for COSENTYX 300 mg (n=82), 58% for COSENTYX 150 mg (n=80) vs 32% for placebo (n=124).¹¹

In FUTURE 5, complete resolution of dactylitis was a prespecified exploratory end point in a subgroup of biologic-naive patients with LDI >0 at baseline at 2 years. No clinical or statistical conclusions can be drawn.¹¹

As with other uncontrolled studies, this phase of the FUTURE 5 study has limitations (eg, no placebo comparisons, and patients responding better are more likely to stay in the study over time).

At baseline, 55 patients and 52 patients had dactylitis in the 300-mg and 150-mg arms, respectively (biologic-naive).¹¹

*Trial used SC administration.
^†Patients with no dactylitis are defined as having an LDI score of 0 among patients with a score of 1 or more at baseline.¹¹

LDI, Leeds Dactylitis Index; NRI, nonresponder imputation; SC, subcutaneous.

In MATURE,* in a mixed population of patients with PsO

In MATURE, a study of patients with PsO, PASI 100 at 1 year was a prespecified exploratory end point in a mixed population. No clinical or statistical conclusions can be drawn.⁸

In FUTURE 5,* as observed in biologic-naive patients with PsA^3,16

• PASI 90 response at 2 years: 71% and 66% for patients on 300 mg (n=68) and 150 mg (n=84), respectively³

• PASI 100 response at 2 years: 50% and 48% for patients on 300 mg (n=68) and 150 mg (n=85), respectively¹⁶

  • 38% of patients with PsA and PsO were up-titrated from 150 mg to 300 mg starting at Week 52, at the investigator's discretion¹⁶

In FUTURE 5, PASI 90 was a prespecified exploratory end point at 2 years. PASI 100 is a post hoc analysis in a subgroup of biologic-naive patients with PsA and PsO based on PASI 75 and PASI 90 as prespecified exploratory end points at 2 years. No clinical or statistical conclusions can be drawn.¹¹

When patients are referred to you from a dermatologist

Have confidence that completely clear skin is possible with COSENTYX

Actual patient photos representative of the average response taken by investigators during PsO clinical trials. Individual results may vary.

*Trials used SC administration.

MI, multiple imputation; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsO, plaque psoriasis; SC, subcutaneous.

In FUTURE 5,^† as observed in biologic-naive patients⁴

Nail clearance at 2 years

150 mg at 2 years: 89% mean improvement in mNAPSI score from baseline (n=78)⁴

46% of patients with nail psoriasis were up-titrated from 150 mg to 300 mg starting at Week 52, at the investigator’s discretion⁴

In FUTURE 5, mNAPSI, a measure used to assess psoriatic nail involvement, was a prespecified exploratory end point in a subgroup of biologic-naive patients with PsA and nail psoriasis. No clinical or statistical conclusions can be drawn.¹¹

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).⁵

At baseline, 66% and 61% of biologic-naive patients had nail psoriasis in the 300-mg and 150-mg arms, respectively. Mean baseline and 2-year mNAPSI values were 19.2 and 3.1, and 19.7 and 2.2, in the 300-mg and 150-mg arms, respectively.^4,11

Real treatment success in patients with nail psoriasis

Actual patient photos representative of the average response taken by investigators during PsO clinical trials. Individual results may vary.

*Other strongly recommended biologics include TNF inhibitors, IL-12/23 inhibitors, and PDE4 inhibitors.
^†Trial used SC administration.

GRAPPA, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis; IL, interleukin; IL-17i, interleukin-17 inhibitor; JAKi, Janus kinase inhibitor; mNAPSI, modified Nail Psoriasis Severity Index; NAPSI, Nail Psoriasis Severity Index; PDE4, phosphodiesterase 4; PsA, psoriatic arthritis; PsO, plaque psoriasis; SC, subcutaneous; TNF, tumor necrosis factor.

• GRAPPA guidelines elevated IL-17i to the level of TNFi—a strong recommendation as a first-line biologic for PsA

• GRAPPA strongly recommends IL-17i, and EULAR recommends using IL-17Ai FIRST for axial PsA

• GRAPPA and EULAR guidelines do NOT recommend IL-23i for axial PsA due to limited/conflicting evidence at this time

*The updated GRAPPA 2021 Guidelines expand on the overarching principles put forth in its 2015 recommendations and are based on systematic literature reviews of data published from 2013 to 2020 taken from Medline, Embase, and the Cochrane Library, including conference presentations from 2017 to 2020. The recommendations used a GRADE-informed methodology (Grading of Recommendations Assessment, Development and Evaluation) to analyze data, and resulted in strong or conditional recommendations, or a decision that no recommendation could be made. Novartis is one of the many corporate supporters of the GRAPPA network.^17
†The updated 2023 EULAR Guidelines expand on the previous 2019 recommendations for the pharmacological management of PsA. Updated recommendations were developed by a steering committee and task force of members from 19 different countries and are based on a systematic literature review from the end of 2018 through April 2023; experience- and consensus-based considerations were also examined. The levels of evidence and grades of recommendation were determined based on the levels of evidence established by the Oxford Centre for Evidence-Based Medicine. Novartis is one of the many corporate supporters of the EULAR network.¹⁹

Hear what your colleagues are saying about this myth in rheumatology 

Dr Amar Majjhoo discusses GRAPPA treatment recommendations for PsA.

GRAPPA, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis; IL-17A, interleukin-17A inhibitor; IL-17i, interleukin-17 inhibitor; IL-23i, interleukin-23 inhibitor; JAKi, Janus kinase inhibitor; PsA, psoriatic arthritis; TNFi, tumor necrosis factor inhibitor.

Dr Amar Majjhoo explores options for inadequate responders with PsA.

PsA, psoriatic arthritis.

COSENTYX clinical trial end points in PsA and PsO

FUTURE 2*
(Two-thirds biologic-naive and one-third anti–TNF-α inadequate responders)¹³

ACR20 responses at Week 16 (NRI) were^6,13:

• 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^6,13:

• 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^6,13

• Improvements in enthesitis and dactylitis scores were observed in the COSENTYX group compared with placebo at Week 24¹³

FUTURE 5*
(Two-thirds biologic-naive and one-third anti–TNF-α inadequate responders)¹¹
Results at Week 16¹¹

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)

MAXIMISE^*§
ASAS20 responses at Week 12 (MI) in biologic-naive patients with PsA were¹:

• 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)

MATURE*
Coprimary end points in patients with moderate to severe PsO (MI)⁷
PASI 75 response at Week 12 (LRM) was: 

• 95% for COSENTYX 300-mg UnoReady^® pen (n=41) (P<0.0001)

• 10% for placebo (n=40) 

IGA mod 2011 0/1 response at Week 12 (LRM) was: 

• 76% for COSENTYX 300-mg UnoReady pen (n=41) (P<0.0001)

• 8% for placebo (n=40)

TRANSFIGURE*
NAPSI improvement at Week 16 in patients with moderate to severe nail PsO (primary end point) (MMRM)^5,20: 

• 46% NAPSI improvement for COSENTYX 300 mg (n=63) (P<0.0001)

• 38% for COSENTYX 150 mg (n=64) (P<0.0001)

• 12% for placebo (n=56)

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.^6,13,21

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).^11,15

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.²²

MATURE was a 52-week, multicenter, randomized, double-blind, placebo-controlled, parallel group study of the efficacy, safety, and tolerability of the 300-mg COSENTYX UnoReady pen in 122 adult patients with moderate to severe PsO. After screening, for Treatment Period 1 (randomization through Week 12 predose), patients were randomized 2:2:1:1 to either COSENTYX 300-mg (2 mL) UnoReady pen, COSENTYX 300-mg 2 × 150-mg (2 × 1 mL) prefilled syringes (PFS), placebo UnoReady pen (2 mL), or placebo (2 × 1 mL) PFS. For Treatment Period 2 (Week 12 through Week 52), PASI 90 nonresponders were rerandomized to the respective COSENTYX 300-mg autoinjector or COSENTYX 300-mg 2 x 1 mL PFS group. All arms started with 4 once-weekly loading doses, followed by dosing every 4 weeks. Patients switched from placebo to active drug repeated the loading doses. Primary end point was the efficacy of the COSENTYX 300-mg UnoReady pen vs placebo, with respect to both PASI 75 and IGA mod 2011 0 or 1 response (coprimary end point) at Week 12.⁸

TRANSFIGURE was a double-blind, randomized, placebo-controlled study examining the safety and efficacy of COSENTYX in patients with moderate to severe nail PsO. Patients were randomized to COSENTYX 300 mg (n=66), COSENTYX 150 mg (n=67), or placebo (n=65). All patients were adults with moderate to severe PsO (PASI score ≥12 and BSA ≥10%) and significant nail involvement (fingernail NAPSI score of ≥16 and ≥4 fingernails involved) who were candidates for systemic therapy. Primary end point: NAPSI assessment at Week 16. Secondary end points included NAPSI response over time up to Week 132.²⁰

Real-world data study designs

Joint, enthesitis, dactylitis, skin, and nail data are sourced from the SERENA study. SERENA was a noninterventional, prospective study conducted across 438 European sites for up to 5 years in patients ≥18 years with moderate to severe PsO, active PsA, or active AS who had received COSENTYX for ≥16 weeks before enrollment. The decision for treatment with COSENTYX had to be made regardless of the noninterventional study, and 2900 patients were enrolled from October 2016 to October 2018. Patients were treated according to local label and data were collected as available in clinical routine. Patients participated in the study for a maximum of 5 years, and visits were documented every 6 months after enrollment. Different effectiveness and QoL parameters evaluated included 78 TJC, 76 SJC (including dactylitis), PGA, total pain VAS, LEI, x-ray assessment, PASI, BSA, and psoriatic nail involvement.^9,23

Axial and 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.¹⁰

Real-world data can supplement data from clinical trials^10,24,25

*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).^5
‡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.^11
§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.⁶

ACR, American College of Rheumatology; AI, autoinjector; AS, ankylosing spondylitis; ASAS, Assessment of SpondyloArthritis International Society criteria; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BSA, body surface area; 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; IGA mod 2011, Investigator’s Global Assessment modified 2011; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; LRM, logistic regression model; MI, multiple imputation; 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; PGA, Physician Global Assessment; PsA, psoriatic arthritis; PsO, plaque psoriasis; SC, subcutaneous; SIR, Italian Society of Rheumatology; SJC, swollen joint counts; TJC, tender joint counts; TNF, tumor necrosis factor; VAS, visual analog scale.