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DISCLOSURES:

  • The comparator (ustekinumab) used in this study was sourced from the US and EU. The US Food and Drug Administration does not consider EU-sourced ustekinumab to be a US-approved product.
  • Secukinumab and ustekinumab are both FDA approved for moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.
  • These products were approved based on pivotal phase III studies that measured 2 coprimary end points (PASI 75 and IGA mod 2011 0/1 [clear/almost clear] or PGA cleared or minimal, respectively) at Week 12. This study has a different primary end point (PASI 90) than those in the pivotal trials for each agent, and was measured at Week 16 instead of Week 12.1,2
  • Please see affiliations of the authors in the downloadable PDF of the reprint. Novartis Pharma AG (Basel, Switzerland) supported this study.

In the 300-mg arm (n=245) of the ERASURE study at Week 121*:

  • 82% of patients achieved PASI 75 at Week 12; of those, 7 out of 10 achieved PASI 90
  • The majority of patients achieved clear or almost clear skin
  • Over 80% of patients on COSENTYX 300 mg in the ERASURE and FIXTURE studies who achieved PASI 75 at Week 12 sustained their response at Week 52§

ERASURE, FIXTURE, JUNCTURE, and FEATURE are the trials that supported the approval of COSENTYX for moderate to severe plaque psoriasis.

*In ERASURE, % of patients achieving an end point on 150 mg vs placebo at Week 12: PASI 75 (71 vs 4), IGA 0 or 1 (51 vs 2), and PASI 90 (39 vs 1). In FIXTURE, results on 300 mg vs placebo at Week 12: PASI 75 (76 vs 5), IGA 0 or 1 (62 vs 3), and PASI 90 (54 vs 2). In FIXTURE, results on 150 mg vs placebo at Week 12: PASI 75 (67 vs 5), IGA 0 or 1 (51 vs 3), and PASI 90 (42 vs 2). P<.0001 for all comparisons. Similar results seen in FEATURE and JUNCTURE.1

In ERASURE, 59% of patients achieved PASI 90 on 300 mg vs 1% for placebo at Week 12.1

In ERASURE, 65% of patients on COSENTYX 300 mg achieved IGA mod 2011 0 or 1 vs 2% of patients on placebo at Week 12.1

§In the COSENTYX 300-mg treatment arm, 81% and 84% of patients in ERASURE and FIXTURE, respectively, who achieved PASI 75 at Week 12 sustained their response at Week 52. In the COSENTYX 150-mg treatment arm, 72% and 82% of patients in ERASURE and FIXTURE, respectively, who achieved PASI 75 at Week 12 sustained their response at Week 52.1

Study Design: The ERASURE and FIXTURE studies were multicenter, randomized, double-blind, placebo-controlled trials. ERASURE evaluated adult patients who received COSENTYX 300 mg (n=245), COSENTYX 150 mg (n=245), or placebo (n=248). FIXTURE evaluated adult patients who received COSENTYX 300 mg (n=327), COSENTYX 150 mg (n=327), placebo (n=326), or a biologic active control (n=323). All patients were adults with moderate to severe plaque psoriasis who had a BSA ≥10%, PASI score ≥12, and IGA mod 2011 score ≥3, and were candidates for systemic therapy or phototherapy. Patients received treatment at Weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. Patients randomized to receive placebo who were nonresponders at Week 12 (did not achieve PASI 75) were then rerandomized to receive COSENTYX 300 mg or 150 mg. All patients were followed for up to 52 weeks. Coprimary end points were PASI 75 and IGA 0 or 1 (clear or almost clear) response at Week 12, evaluated using nonresponder imputation analysis (NRI).1,3,4

IGA=Investigator's Global Assessment; PASI=Psoriasis Area and Severity Index; PGA=Physician Global Assessment.

References: 1. Cosentyx [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 2. Thaçi D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol. 2015;73(3):400-409. 3. Data on file. AIN457A2302 Clinical Study Report. Novartis Pharmaceuticals Corp; September 2013. 4. Data on file. AIN457A2303 Clinical Study Report. Novartis Pharmaceuticals Corp; September 2013.

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.

WARNINGS AND PRECAUTIONS

Infections

COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in subjects treated with COSENTYX compared to placebo-treated subjects. In placebo-controlled clinical trials in patients with moderate to severe plaque psoriasis, 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 with COSENTYX compared with placebo. A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic arthritis. The incidence of some types of infections appeared to be dose-dependent in clinical studies.

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, the patient should be closely monitored and COSENTYX should be discontinued until the infection resolves.

Pre-treatment Evaluation for Tuberculosis

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX. Do not administer 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. Patients receiving COSENTYX should be monitored closely for signs and symptoms of active TB during and after treatment.

Inflammatory Bowel Disease

Caution should be used when prescribing COSENTYX to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred in patients treated with COSENTYX during clinical trials in plaque psoriasis and psoriatic arthritis. In addition, new onset inflammatory bowel disease cases occurred in clinical trials with COSENTYX. In an exploratory study in 59 patients with active Crohn's disease, there were trends toward greater disease activity and increased adverse events in the secukinumab group as compared to the placebo group. Patients who are treated with COSENTYX should be monitored for signs and symptoms of inflammatory bowel disease.

Hypersensitivity Reactions

Anaphylaxis and cases of urticaria occurred in patients treated with COSENTYX in clinical trials. If an anaphylactic or other serious allergic reaction occurs, administration of COSENTYX should be discontinued immediately and appropriate therapy initiated.

The removable cap of the COSENTYX Sensoready® pen and the COSENTYX prefilled syringe contains 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.

Vaccinations

Prior to initiating therapy with COSENTYX, consider completion of all age appropriate immunizations according to current immunization guidelines. Patients treated with COSENTYX should not receive live vaccines.

Non-live vaccinations received during a course of COSENTYX may not elicit an immune response sufficient to prevent disease.

MOST COMMON ADVERSE REACTIONS

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

INDICATIONS

COSENTYX is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

COSENTYX is indicated for the treatment of adult patients with active psoriatic arthritis.

Please see link to full Prescribing Information, including Medication Guide, in the upper right hand corner of the home page.

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IMPORTANT SAFETY INFORMATION AND INDICATIONS

CONTRAINDICATIONS

COSENTYX® (secukinumab) is contraindicated in patients with a previous serious hypersensitivity reaction to secukinumab or to any of the excipients.

WARNINGS AND PRECAUTIONS

Infections

COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in subjects treated with COSENTYX compared to placebo-treated subjects. In placebo-controlled clinical trials in patients with moderate to severe plaque psoriasis, 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 with COSENTYX compared with placebo. A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic arthritis. The incidence of some types of infections appeared to be dose-dependent in clinical studies. 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, the patient should be closely monitored and COSENTYX should be discontinued until the infection resolves.

Pre-treatment Evaluation for Tuberculosis

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX. Do not administer 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. Patients receiving COSENTYX should be monitored closely for signs and symptoms of active TB during and after treatment.

Inflammatory Bowel Disease

Caution should be used when prescribing COSENTYX to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred in patients treated with COSENTYX during clinical trials in plaque psoriasis and psoriatic arthritis. In addition, new onset inflammatory bowel disease cases occurred in clinical trials with COSENTYX. In an exploratory study in 59 patients with active Crohn’s disease, there were trends toward greater disease activity and increased adverse events in the secukinumab group as compared to the placebo group. Patients who are treated with COSENTYX should be monitored for signs and symptoms of inflammatory bowel disease.

Hypersensitivity Reactions

Anaphylaxis and cases of urticaria occurred in patients treated with COSENTYX in clinical trials. If an anaphylactic or other serious allergic reaction occurs, administration of COSENTYX should be discontinued immediately and appropriate therapy initiated.

The removable cap of the COSENTYX Sensoready® pen and the COSENTYX prefilled syringe contains 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.

Vaccinations

Prior to initiating therapy with COSENTYX, consider completion of all age appropriate immunizations according to current immunization guidelines. Patients treated with COSENTYX should not receive live vaccines. Non-live vaccinations received during a course of COSENTYX may not elicit an immune response sufficient to prevent disease.

MOST COMMON ADVERSE REACTIONS

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

INDICATIONS

COSENTYX is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

COSENTYX is indicated for the treatment of adult patients with active psoriatic arthritis.

16-WEEK RESULTS FROM
THE CLEAR TRIAL

line

Secukinumab is superior to ustekinumab in clearing skin of subjects with

moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial

Thaçi D, Blauvelt A, Reich K, et al. J Am Acad Dermatol. 2015;73(3):400-409.

Summary

OBJECTIVE: Directly compare efficacy and safety of secukinumab versus ustekinumab.

METHODS:

  • In this double-blind study (NCT02074982), 676 subjects were randomized 1:1 to subcutaneous injection of secukinumab 300 mg or ustekinumab per prescribing information.
  • Results presented here are the 16-week analysis of the 52-week study.
  • Primary end point was 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI) score (PASI 90) at Week 16.

RESULTS:

  • Secukinumab (79.0%) was superior to ustekinumab (57.6%) as assessed by PASI 90 response at Week 16 (P<.0001).
  • The 75% or more improvement from baseline PASI score (PASI 75) at Week 4 was superior for secukinumab (50.0%) versus ustekinumab (20.6%) (P<.0001).
  • The 100% improvement from baseline PASI score (PASI 100) at Week 16 was also greater with secukinumab (44.3%) than ustekinumab (28.4%).
  • At Week 16, the safety profile of secukinumab was comparable with ustekinumab and consistent with pivotal phase III secukinumab studies.

LIMITATIONS:

  • The study does not have a placebo arm, which might explain the slightly higher response rates observed with secukinumab and ustekinumab when compared with the corresponding rates reported in previous placebo-controlled studies. Cross-study comparisons, however, must be viewed with caution.
  • The duration of the current primary analysis (16 weeks) may not be long enough to detect all rare AEs or AEs with long latency. In addition, details of rare AEs were not reported in this article according to the treatment arms in the current analysis to maintain blinding.

DISCLOSURES:

  • The comparator (ustekinumab) used in this study was sourced from the US and EU. The US Food and Drug Administration does not consider EU-sourced ustekinumab to be a US-approved product.
  • Secukinumab and ustekinumab are both FDA approved for moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.
  • These products were approved based on pivotal phase III studies that measured 2 coprimary end points
    (PASI 75 and IGA mod 2011 0/1 [clear/almost clear] or PGA cleared or minimal, respectively) at Week 12. This study has a different primary end point (PASI 90) than those in the pivotal trials for each agent, and was measured at Week 16 instead of Week 12.
  • Please see affiliations of the authors in the downloadable PDF of the reprint. Novartis Pharma AG (Basel, Switzerland) supported this study.

Study schema

16-Week Study Design, Secukinumab vs. Ustekinumab End Points

Study subjects: Adult patients with moderate to severe plaque psoriasis

Secondary end point*: PASI 75 at Week 4

Exploratory end points*:

  • – PASI 75/90/100 over time
  • – IGA mod 2011 0/1 (clear/almost clear) response over time

Note: Exploratory end points do not meet the statistical rigor needed to draw conclusions about observed results and therefore should be interpreted with caution.

Please see study design here for additional details.

*Other end points evaluated in the study are not included in this presentation.

PASI 90 and PASI 75 response rates over time

16-Week Study Design, Primary End Point PASI 90 Exploratory End Point, PASI 75 at Week 16

Note: Exploratory end points do not meet the statistical rigor needed to draw conclusions about observed results and therefore should be interpreted with caution.

*Missing values for PASI score response variables and IGA mod 2011 0/1 (clear/almost clear) response were imputed as nonresponses (nonresponder imputation).

PASI 100 and IGA 0/1 (clear/almost clear)
response rates over time

Exploratory End Point, PASI 100 at Week 16 Exploratory End Point, IGA mod 2011 0/1 Response at Week 52

Note: Exploratory end points do not meet the statistical rigor needed to draw conclusions about observed results and therefore should be interpreted with caution.

*Missing values for PASI score response variables and IGA mod 2011 0/1 (clear/almost clear) response were imputed as nonresponses (nonresponder imputation).

Score of 0 (clear) or 1 (almost clear) and an improvement of ≥2 points from baseline.

Safety summary

  • No new or unexpected safety signals were identified for secukinumab during the 16-week treatment period
  • At Week 16, secukinumab exhibited a safety profile similar to that of ustekinumab and consistent with that seen in secukinumab pivotal phase III trials

Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial

Thaçi D, Blauvelt A, Reich K, et al. J Am Acad Dermatol. 2015;73(3):400-409.

Click to Access the Publication

CLEAR STUDY DESIGN

The CLEAR study was a phase IIIb, 52-week randomized, double-blind, active-comparator study. CLEAR evaluated adult patients with moderate to severe plaque psoriasis who were randomized 1:1 to receive secukinumab 300 mg (n=337) or ustekinumab 45 mg (for subjects ≤100 kg at baseline) or 90 mg (>100 kg at baseline) at baseline (n=339). Subjects had a diagnosis of moderate to severe plaque psoriasis (defined as: PASI score ≥12, BSA ≥10%, and IGA mod 2011 ≥3) at least 6 months before randomization and had been inadequately controlled by topical treatments, phototherapy, and/or previous systemic therapy. Key exclusion criteria included previous exposure to any biologics directly targeting IL-17A/IL-17 receptor A or IL-12/23. Patients received secukinumab at Weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter to Week 48. Patients received ustekinumab at Weeks 0, 4, and every 12 weeks thereafter from Week 16 to Week 40 with matching secukinumab regimen placebo injections given to maintain blinding. Primary end point was PASI 90 at Week 16. Secondary end points were PASI 75 response rates at Week 4 and PASI 90 response rates at Week 52.1,2

16-Week Study Design, Baseline Demographics

PASI scores range from 0 (no disease) to 72 (maximal disease). IGA mod 2011 scores range from 0 (clear skin) to 4 (severe disease). Data are given as n (%) or mean ± SD.

BMI=body mass index; BSA=body surface area; IGA=Investigator’s Global Assessment; PASI=Psoriasis Area and Severity Index.

*All other subjects had a score of 3 (moderate disease), with the exception of 2 subjects who were recorded at baseline as having a score of 2 (mild disease), which was corrected to a score of 3 after the Week 16 database lock.

Included methotrexate, cyclosporine, corticosteroids, and fumaric acid esters.

Adapted with permission from Thaçi D et al. J Am Acad Dermatol. 2015;73(3):400-409.

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.

WARNINGS AND PRECAUTIONS

Infections

COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in subjects treated with COSENTYX compared to placebo-treated subjects. In placebo-controlled clinical trials in patients with moderate to severe plaque psoriasis, 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 with COSENTYX compared with placebo. A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic arthritis. The incidence of some types of infections appeared to be dose-dependent in clinical studies.

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, the patient should be closely monitored and COSENTYX should be discontinued until the infection resolves.

Pre-treatment Evaluation for Tuberculosis

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX. Do not administer 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. Patients receiving COSENTYX should be monitored closely for signs and symptoms of active TB during and after treatment.

Inflammatory Bowel Disease

Caution should be used when prescribing COSENTYX to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred in patients treated with COSENTYX during clinical trials in plaque psoriasis and psoriatic arthritis. In addition, new onset inflammatory bowel disease cases occurred in clinical trials with COSENTYX. In an exploratory study in 59 patients with active Crohn’s disease, there were trends toward greater disease activity and increased adverse events in the secukinumab group as compared to the placebo group. Patients who are treated with COSENTYX should be monitored for signs and symptoms of inflammatory bowel disease.

Hypersensitivity Reactions

Anaphylaxis and cases of urticaria occurred in patients treated with COSENTYX in clinical trials. If an anaphylactic or other serious allergic reaction occurs, administration of COSENTYX should be discontinued immediately and appropriate therapy initiated.

The removable cap of the COSENTYX Sensoready® pen and the COSENTYX prefilled syringe contains 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.

Vaccinations

Prior to initiating therapy with COSENTYX, consider completion of all age appropriate immunizations according to current immunization guidelines. Patients treated with COSENTYX should not receive live vaccines.

Non-live vaccinations received during a course of COSENTYX may not elicit an immune response sufficient to prevent disease.

MOST COMMON ADVERSE REACTIONS

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

INDICATIONS

COSENTYX is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

COSENTYX is indicated for the treatment of adult patients with active psoriatic arthritis.

Please see full Prescribing Information, including Medication Guide.

References: 1. Thaçi D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol. 2015;73(3):400-409. 2. Blauvelt A, Reich K, Tsai TF, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis up to 1 year: Results from the CLEAR study. J Am Acad Dermatol. 2017;76(1):60-69.