Cosentyx 75mg solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC) (2025)

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC10

Mechanism of action

Secukinumab is a fully human IgG1/κ monoclonal antibody that selectively binds to and neutralises the proinflammatory cytokine interleukin-17A (IL-17A). Secukinumab works by targeting IL-17A and inhibiting its interaction with the IL-17 receptor, which is expressed on various cell types including keratinocytes. As a result, secukinumab inhibits the release of proinflammatory cytokines, chemokines and mediators of tissue damage and reduces IL-17A-mediated contributions to autoimmune and inflammatory diseases. Clinically relevant levels of secukinumab reach the skin and reduce local inflammatory markers. As a direct consequence treatment with secukinumab reduces erythema, induration and desquamation present in plaque psoriasis lesions.

IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. IL-17A plays a key role in the pathogenesis of plaque psoriasis, psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) and is up-regulated in lesional skin in contrast to non-lesional skin of plaque psoriasis patients and in synovial tissue of psoriatic arthritis patients. The frequency of IL-17-producing cells was also significantly higher in the subchondral bone marrow of facet joints from patients with ankylosing spondylitis. Increased numbers of IL-17A producing lymphocytes have also been found in patients with non-radiographic axial spondyloarthritis. Inhibition of IL-17A was shown to be effective in the treatment of ankylosing spondylitis, thus establishing the key role of this cytokine in axial spondyloarthritis.

Pharmacodynamic effects

Serum levels of total IL-17A (free and secukinumab-bound IL-17A) are initially increased in patients receiving secukinumab. This is followed by a slow decrease due to reduced clearance of secukinumab-bound IL-17A, indicating that secukinumab selectively captures free IL-17A, which plays a key role in the pathogenesis of plaque psoriasis.

In a study with secukinumab, infiltrating epidermal neutrophils and various neutrophil-associated markers that are increased in lesional skin of plaque psoriasis patients were significantly reduced after one to two weeks of treatment.

Secukinumab has been shown to lower (within 1 to 2 weeks of treatment) levels of C-reactive protein, which is a marker of inflammation.

Clinical efficacy and safety

Adult plaque psoriasis

The safety and efficacy of secukinumab were assessed in four randomised, double-blind, placebo-controlled phase III studies in patients with moderate to severe plaque psoriasis who were candidates for phototherapy or systemic therapy [ERASURE, FIXTURE, FEATURE, JUNCTURE]. The efficacy and safety of secukinumab 150 mg and 300 mg were evaluated versus either placebo or etanercept. In addition, one study assessed a chronic treatment regimen versus a “ retreatment as needed” regimen [SCULPTURE].

Of the 2 403 patients who were included in the placebo-controlled studies, 79% were biologic-naive, 45% were non-biologic failures and 8% were biologic failures (6% were anti-TNF failures, and 2% were anti-p40 failures). Approximately 15 to 25% of patients in phase III studies had psoriatic arthritis (PsA) at baseline.

Psoriasis study 1 (ERASURE) evaluated 738 patients. Patients randomised to secukinumab received 150 mg or 300 mg doses at weeks 0, 1, 2, 3 and 4, followed by the same dose every month. Psoriasis study 2 (FIXTURE) evaluated 1 306 patients. Patients randomised to secukinumab received 150 mg or 300 mg doses at weeks 0, 1, 2, 3 and 4, followed by the same dose every month. Patients randomised to etanercept received 50 mg doses twice per week for 12 weeks followed by 50 mg every week. In both study 1 and study 2, patients randomised to receive placebo who were non-responders at week 12 then crossed over to receive secukinumab (either 150 mg or 300 mg) at weeks 12, 13, 14, and 15, followed by the same dose every month starting at week 16. All patients were followed for up to 52 weeks following first administration of study treatment.

Psoriasis study 3 (FEATURE) evaluated 177 patients using a pre-filled syringe compared with placebo after 12 weeks of treatment to assess the safety, tolerability, and usability of secukinumab self-administration via the pre-filled syringe. Psoriasis study 4 (JUNCTURE) evaluated 182 patients using a pre-filled pen compared with placebo after 12 weeks of treatment to assess the safety, tolerability, and usability of secukinumab self-administration via the pre-filled pen. In both study 3 and study 4, patients randomised to secukinumab received 150 mg or 300 mg doses at weeks 0, 1, 2, 3 and 4, followed by the same dose every month. Patients were also randomised to receive placebo at weeks 0, 1, 2, 3 and 4, followed by the same dose every month.

Psoriasis study 5 (SCULPTURE) evaluated 966 patients. All patients received secukinumab 150 mg or 300 mg doses at weeks 0, 1, 2, 3, 4, 8 and 12 and then were randomised to receive either a maintenance regimen of the same dose every month starting at week 12 or a “ retreatment as needed” regimen of the same dose. Patients randomised to “ retreatment as needed” did not achieve adequate maintenance of response and therefore a fixed monthly maintenance regimen is recommended.

The co-primary endpoints in the placebo and active-controlled studies were the proportion of patients who achieved a PASI 75 response and IGA mod 2011 “ clear” or “ almost clear” response versus placebo at week 12 (see Tables 4 and 5). The 300 mg dose provided improved skin clearance particularly for “ clear” or “ almost clear” skin across the efficacy endpoints of PASI 90, PASI 100, and IGA mod 2011 0 or 1 response across all studies with peak effects seen at week 16, therefore this dose is recommended.

Table 4 Summary of PASI 50/75/90/100 & IGA* mod 2011 “ clear” or “ almost clear” clinical response in psoriasis studies 1, 3 and 4 (ERASURE, FEATURE and JUNCTURE)

Table 5 Summary of clinical response on psoriasis study 2 (FIXTURE)

** p-values versus etanercept: p=0.0250

In an additional psoriasis study (CLEAR) 676 patients were evaluated. Secukinumab 300 mg met the primary and secondary endpoints by showing superiority to ustekinumab based on PASI 90 response at week 16 (primary endpoint), speed of onset of PASI 75 response at week 4, and long-term PASI 90 response at week 52. Greater efficacy of secukinumab compared to ustekinumab for the endpoints PASI 75/90/100 and IGA mod 2011 0 or 1 response (“ clear” or “ almost clear” ) was observed early and continued through to week 52 (Table 6).

Table 6 Summary of clinical response on CLEAR study

* Patients treated with secukinumab received 300 mg doses at weeks 0, 1, 2 3 and 4, followed by the same dose every 4 weeks until week 52. Patients treated with ustekinumab received 45 mg or 90 mg at weeks 0 and 4, then every 12 weeks until week 52 (dosed by weight as per approved posology)

** p-values versus ustekinumab: p<0.0001 for primary endpoint of PASI 90 at week 16 and secondary endpoint of PASI 75 at week 4

*** p-values versus ustekinumab: p=0.0001 for secondary endpoint of PASI 90 at week 52

Secukinumab was efficacious in systemic treatment-naive, biologic-naive, biologic/anti-TNF-exposed and biologic/anti-TNF-failure patients. Improvements in PASI 75 in patients with concurrent psoriatic arthritis at baseline were similar to those in the overall plaque psoriasis population.

Secukinumab was associated with a fast onset of efficacy with a 50% reduction in mean PASI by week 3 for the 300 mg dose.

Figure 1 Time course of percentage change from baseline of mean PASI score in study 1 (ERASURE)

Specific locations/forms of plaque psoriasis

In two additional placebo-controlled studies, improvement was seen in both nail psoriasis (TRANSFIGURE, 198 patients) and palmoplantar plaque psoriasis (GESTURE, 205 patients). In the TRANSFIGURE study, secukinumab was superior to placebo at week 16 (46.1% for 300 mg, 38.4% for 150 mg and 11.7% for placebo) as assessed by significant improvement from baseline in the Nail Psoriasis Severity Index (NAPSI %) for patients with moderate to severe plaque psoriasis with nail involvement. In the GESTURE study, secukinumab was superior to placebo at week 16 (33.3% for 300 mg, 22.1% for 150 mg, and 1.5% for placebo) as assessed by significant improvement of ppIGA 0 or 1 response (“ clear” or “ almost clear” ) for patients with moderate to severe palmoplantar plaque psoriasis.

A placebo-controlled study evaluated 102 patients with moderate to severe scalp psoriasis, defined as having a Psoriasis Scalp Severity Index (PSSI) score of ≥ 12, an IGA mod 2011 scalp only score of 3 or greater and at least 30% of the scalp surface area affected. Secukinumab 300 mg was superior to placebo at week 12 as assessed by significant improvement from baseline in both the PSSI 90 response (52.9% versus 2.0%) and IGA mod 2011 0 or 1 scalp only response (56.9% versus 5.9%). Improvement in both endpoints was sustained for secukinumab patients who continued treatment through to week 24.

Quality of life/patient-reported outcomes

Statistically significant improvements at week 12 (studies 1-4) from baseline compared to placebo were demonstrated in the DLQI (Dermatology Life Quality Index). Mean decreases (improvements) in DLQI from baseline ranged from -10.4 to -11.6 with secukinumab 300 mg, from -7.7 to -10.1 with secukinumab 150 mg, versus -1.1 to -1.9 for placebo at week 12. These improvements were maintained for 52 weeks (studies 1 and 2).

Forty percent of the participants in studies 1 and 2 completed the Psoriasis Symptom Diary^© . For the participants completing the diary in each of these studies, statistically significant improvements at week 12 from baseline compared to placebo in patient-reported signs and symptoms of itching, pain and scaling were demonstrated.

Statistically significant improvements at week 4 from baseline in patients treated with secukinumab compared to patients treated with ustekinumab (CLEAR) were demonstrated in the DLQI and these improvements were maintained for up to 52 weeks.

Statistically significant improvements in patient-reported signs and symptoms of itching, pain and scaling at week 16 and week 52 (CLEAR) were demonstrated in the Psoriasis Symptom Diary^© in patients treated with secukinumab compared to patients treated with ustekinumab.

Statistically significant improvements (decreases) at week 12 from baseline in the scalp psoriasis study were demonstrated in patient reported signs and symptoms of scalp itching, pain and scaling compared to placebo.

Paediatric population

Paediatric plaque psoriasis

Secukinumab has been shown to improve signs and symptoms, and health-related quality of life in paediatric patients 6 years and older with plaque psoriasis (see Tables 8 and 10).

Severe plaque psoriasis

The safety and efficacy of secukinumab were assessed in a randomised, double-blind, placebo and etanercept-controlled phase III study in paediatric patients from 6 to <18 years of age with severe plaque psoriasis, as defined by a PASI score ≥ 20, an IGA mod 2011 score of 4, and BSA involvement of ≥ 10%, who were candidates for systemic therapy. Approximately 43% of the patients had prior exposure to phototherapy, 53% to conventional systemic therapy, 3% to biologics, and 9% had concomitant psoriatic arthritis.

The paediatric psoriasis study 1 evaluated 162 patients who were randomised to receive low dose secukinumab (75 mg for body weight <50 kg or 150 mg for body weight ≥ 50 kg), high dose secukinumab (75 mg for body weight <25 kg, 150 mg for body weight between ≥ 25 kg and <50 kg, or 300 mg for body weight ≥ 50 kg), or placebo at weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks, or etanercept. Patients randomised to etanercept received 0.8 mg/kg weekly (up to a maximum of 50 mg). Patient distribution by weight and age at randomisation is described in Table 7.

Table 7 Patient distribution by weight and age for paediatric psoriasis study 1

Patients randomised to receive placebo who were non-responders at week 12 were switched to either the secukinumab low or high dose group (dose based on body weight group) and received study drug at weeks 12, 13, 14, and 15, followed by the same dose every 4 weeks starting at week 16. The co-primary endpoints were the proportion of patients who achieved a PASI 75 response and IGA mod 2011 'clear' or 'almost clear' (0 or 1) response at week 12.

During the 12 week placebo-controlled period, the efficacy of both the low and the high dose of secukinumab was comparable for the co-primary endpoints. The odds ratio estimates in favour of both secukinumab doses were statistically significant for both the PASI 75 and IGA mod 2011 0 or 1 responses.

All patients were followed for efficacy and safety during the 52 weeks following the first dose. The proportion of patients achieving PASI 75 and IGA mod 2011 'clear' or 'almost clear' (0 or 1) responses showed separation between secukinumab treatment groups and placebo at the first post-baseline visit at week 4, the difference becoming more prominent at week 12. The response was maintained throughout the 52 week time period (see Table 8). Improvement in PASI 50, 90, 100 responder rates and Children's Dermatology Life Quality Index (CDLQI) scores of 0 or 1 were also maintained throughout the 52 week time period.

In addition, PASI 75, IGA 0 or 1, PASI 90 response rates at weeks 12 and 52 for both secukinumab low and high dose groups were higher than the rates for patients treated with etanercept (see Table 8).

Beyond week 12, efficacy of both the low and the high dose of secukinumab was comparable although the efficacy of the high dose was higher for patients ≥ 50 kg. The safety profiles of the low dose and the high dose were comparable and consistent with the safety profile in adults.

Table 8 Summary of clinical response in severe paediatric psoriasis at weeks 12 and 52 (paediatric psoriasis study 1)*

A higher proportion of paediatric patients treated with secukinumab reported improvement in health-related quality of life as measured by a CDLQI score of 0 or 1 compared to placebo at week 12 (low dose 44.7%, high dose 50%, placebo 15%). Over time up to and including week 52 both secukinumab dose groups were numerically higher than the etanercept group (low dose 60.6%, high dose 66.7%, etanercept 44.4%).

Moderate to severe plaque psoriasis

Secukinumab was predicted to be effective for the treatment of paediatric patients with moderate plaque psoriasis based on the demonstrated efficacy and exposure response relationship in adult patients with moderate to severe plaque psoriasis, and the similarity of the disease course, pathophysiology, and drug effect in adult and paediatric patients at the same exposure levels.

Moreover, the safety and efficacy of secukinumab was assessed in an open-label, two-arm, parallel-group, multicentre phase III study in paediatric patients from 6 to <18 years of age with moderate to severe plaque psoriasis, as defined by a PASI score ≥ 12, an IGA mod 2011 score of ≥ 3, and BSA involvement of ≥ 10%, who were candidates for systemic therapy.

The paediatric psoriasis study 2 evaluated 84 patients who were randomised to receive low dose secukinumab (75 mg for body weight <50 kg or 150 mg for body weight ≥ 50 kg) or high dose secukinumab (75 mg for body weight <25 kg, 150 mg for body weight between ≥ 25 kg and <50 kg, or 300 mg for body weight ≥ 50 kg) at weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks. Patient distribution by weight and age at randomisation is described in Table 9.

Table 9 Patient distribution by weight and age for paediatric psoriasis study 2

The co-primary endpoints were the proportion of patients who achieved a PASI 75 response and IGA mod 2011 'clear' or 'almost clear' (0 or 1) response at week 12.

The efficacy of both the low and the high dose of secukinumab was comparable and showed statistically significant improvement compared to historical placebo for the co-primary endpoints. The estimated posterior probability of a positive treatment effect was 100%.

Patients were followed for efficacy over a 52 week period after first administration. Efficacy (defined as PASI 75 response and IGA mod 2011 'clear' or 'almost clear' [0 or 1]) was observed as early as the first post-baseline visit at week 2, and the proportion of patients who achieved a PASI 75 response and IGA mod 2011 'clear' or 'almost clear' (0 or 1) increased up to week 24 and were sustained until week 52. Improvement in PASI 90 and PASI 100 were also observed at week 12, increased up to week 24, and were sustained until week 52 (see Table 10).

The safety profiles of the low dose and the high dose were comparable and consistent with the safety profile in adults.

Table 10 Summary of clinical response in moderate to severe paediatric psoriasis at weeks 12 and 52 (paediatric psoriasis study 2)*

These outcomes in the paediatric moderate to severe plaque psoriasis population confirmed the predictive assumptions based on the efficacy and exposure response relationship in adult patients, mentioned above.

In the low dose group, 50% and 70.7% of patients achieved a CDLQI 0 or 1 score at weeks 12 and 52, respectively. In the high dose group, 61.9% and 70.3% achieved a CDLQI 0 or 1 score at weeks 12 and 52, respectively.

Juvenile idiopathic arthritis (JIA)

Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA)

The efficacy and safety of secukinumab were assessed in 86 patients in a 3-part, double-blind, placebo-controlled, event-driven, randomised, phase III study in patients 2 to <18 years of age with active ERA or JPsA as diagnosed based on a modified International League of Associations for Rheumatology (ILAR) JIA classification criteria. The study consisted of an open-label portion (Part 1) where all patients received secukinumab until week 12. Patients demonstrating a JIA ACR 30 response at week 12 entered into the Part 2 double-blind phase and were randomised 1:1 to continue treatment with secukinumab or to begin treatment with placebo (randomised withdrawal) until week 104 or until a flare occured. Patients who flared then entered open-label secukinumab treatment until week 104 (Part 3).

The JIA patient subtypes at study entry were: 60.5% ERA and 39.5% JPsA, who either had inadequate response or were intolerant to ≥ 1 disease-modifying antirheumatic drugs (DMARDs) and ≥ 1 non-steroidal anti-inflammatory drugs (NSAIDs). At baseline, MTX use was reported for 65.1% of patients; (63.5% [33/52] of ERA patients and 67.6% [23/34] of JPsA patients). There were 12 out of 52 ERA patients concomitantly treated with sulfasalazine (23.1%). Patients with a body weight at baseline <50 kg (n=30) were given a dose of 75 mg and patients with a body weight ≥ 50 kg (n=56) were given a dose of 150 mg. Age at baseline ranged from 2 to 17 years, with 3 patients between 2 to <6 years, 22 patients 6 to <12 years and 61 patients 12 to <18 years. At baseline the Juvenile Arthritis Disease Activity Score (JADAS)-27 was 15.1 (SD:7.1).

The primary endpoint was time to flare in the randomised withdrawal period (Part 2). Disease flare was defined as a ≥ 30% worsening in at least three of the six JIA ACR response criteria and ≥ 30% improvement in not more than one of the six JIA ACR response criteria and a minimum of two active joints.

At the end of Part 1, 75 out of 86 (87.2%) patients demonstrated a JIA ACR 30 response and entered into Part 2.

The study met its primary endpoint by demonstrating a statistically significant prolongation in the time to disease flare in patients treated with secukinumab compared to placebo in Part 2. The risk of flare was reduced by 72% for patients on secukinumab compared with patients on placebo in Part 2 (Hazard ratio=0.28, 95% CI: 0.13 to 0.63, p<0.001) (Figure 2 and Table 11). During Part 2, a total of 21 patients in the placebo group experienced a flare event (11 JPsA and 10 ERA) compared with 10 patients in the secukinumab group (4 JPsA and 6 ERA).

Figure 2 Kaplan-Meier estimates of the time to disease flare in Part 2

Table 11 Survival analysis of time to disease flare – Part 2

In open-label Part 1, all patients received secukinumab until week 12. At week 12, 83.7%, 67.4%, and 38.4% of children were JIA ACR 50, 70 and 90 responders, respectively (Figure 3). The onset of action of secukinumab occurred as early as week 1. At week 12 the JADAS-27 score was 4.64 (SD:4.73) and the mean decrease from baseline in JADAS-27 was -10.487 (SD:7.23).

Figure 3 JIA ACR 30/50/70/90 response for subjects up to week 12 in Part 1*

*non-responder imputation was used to handle missing values

The data in the 2 to <6 age group were inconclusive due to the low number of patients below 6 years of age enrolled in the study.

The licensing authority has waived the obligation to submit the results of studies with Cosentyx in plaque psoriasis in paediatric patients aged from birth to less than 6 years and in chronic idiopathic arthritis for paediatric patients aged from birth to less than 2 years (see section 4.2 for information on paediatric use).