Secukinumab (1) – Cosentyx®

a) Patient population A – Treatment of adult patients with moderate to severe plaque psoriasis who are suitable for systemic and/or phototherapy.

• There is no evidence of any additional benefit of secukinumab compared with the appropriate comparator therapy (standard therapy optimised for the individual patient, taking into account fumaric acid esters, ciclosporin, methotrexate or phototherapy [balneophototherapy, oral PUVA, NB-UVB]) is not proven.
• Due to the lack of direct comparative studies for patient population A, the pharmaceutical manufacturer carried out an indirect comparison of secukinumab with methotrexate, using placebo as the bridge comparator.
• In summary, no conclusions regarding the additional benefit of secukinumab for the treatment of adult patients with moderate to severe plaque psoriasis who are suitable for systemic and/or phototherapy can be drawn from the submitted indirect comparison of secukinumab with methotrexate, particularly given that the studies selected for the comparator therapy had an insufficiently long study duration.
• The additional benefit of secukinumab for the treatment of adult patients with moderate to severe plaque psoriasis who are suitable for systemic and/or phototherapy is not proven.

b1) Patient population B – Treatment of adult patients with moderate to severe plaque psoriasis who have had an inadequate response to other systemic therapies, including ciclosporin, methotrexate or PUVA (psoralen and ultraviolet A light), or who have a contraindication to or are intolerant of such therapies.– Patient population B 1) Patients with prior treatment with biologics

• There is an indication of considerable additional benefit from secukinumab compared with the appropriate comparator therapy (adalimumab or infliximab or ustekinumab).
• Overall, the positive effects of secukinumab on all morbidity endpoints investigated and on health-related quality of life, without any disadvantages in terms of side effects for patient population B1 (with prior treatment with biologics) are assessed as a significant improvement in treatment-related benefit – within the meaning of Section 2(3) – that has not previously been achieved compared with the appropriate comparator therapy, and the extent of the additional benefit is classified as considerable.
• mortality
  • For the patient-relevant endpoint of overall mortality, no statistically significant difference was observed between the treatment groups.
  • Consequently, there is no additional benefit of secukinumab compared with ustekinumab; an additional benefit for overall survival is therefore not proven.
• Morbidity – Symptoms (pain)
  • For the patient population with prior biologic therapy, there is a statistically significant difference in favour of secukinumab compared with ustekinumab (treatment group difference: MD −1.77 [95% CI −2.91; −0.63]; p-value 0.002), whilst no significant difference between the treatment groups was observed in the population without prior biologic therapy (MD −0.07 [95% CI −0.57; 0.43]; p-value 0.788).
  • For patients who had previously been treated with a biologic (patient population B1), a statistically significant difference in favour of secukinumab was observed in each case.
  • The 95% confidence interval for each was entirely below the non-significance threshold, suggesting clinically relevant effects on these patient-relevant endpoints.
• Morbidity – Symptoms (itching)
  • There is proof of an effect modification by the characteristic of prior treatment with biologics (p-value = 0.004), therefore, for patients with a history of biologic therapy, there is a statistically significant difference in favour of secukinumab compared with ustekinumab (treatment group difference: MD −2.35 [95% CI −3.62; −1.08] p-value < 0.001).
  • For patients with a history of treatment with a biologic (patient population B1), a statistically significant difference in favour of secukinumab was observed in each case.
  • The 95% confidence interval lay entirely below the non-significance threshold in each case, suggesting clinically relevant effects on these patient-relevant endpoints.
• Morbidity – Symptoms (scaling)
  • Patients with a history of biologic therapy showed a significant improvement in the scaling endpoint in the secukinumab arm compared with the ustekinumab arm.
  • Consequently, for patients with a history of biologic therapy, there is a statistically significant difference in favour of secukinumab compared with ustekinumab (difference between treatment groups: MD −1.88 [95% CI −3.04; −0.71]; p-value 0.002).
  • For patients who had previously received biologic therapy (patient population B1), a statistically significant difference in favour of secukinumab was observed in each case.
  • The 95% confidence interval lay entirely below the non-significance threshold in each case, suggesting clinically relevant effects on these patient-relevant endpoints.
• Morbidity – Remission (PASI 100)
  • For the endpoint ‘cumulative proportion of patients who achieved PASI 100 during the course of the study’, a statistically significant difference in favour of secukinumab was observed (based on the Kaplan-Meier estimator) (PASI 100: HR: 1.52 [95% CI 1.14; 2.02]; p-value 0.005).
  • Overall, it is assumed that secukinumab has a positive effect on remission compared with ustekinumab; however, the results are subject to increased uncertainty.
  • From this, an additional benefit of secukinumab over ustekinumab can be inferred.
• Morbidity – Response (PASI 75 and PASI 90)
  • For both response thresholds, PASI 75 and PASI 90, an increase was observed in the proportion of patients achieving a response (PASI 75: RR 1.23 [95% CI 1.08; 1.41]; p-value 0.001; PASI 90: RR 1.28 [95% CI 1.06–1.54]; p-value 0.008) and in terms of the cumulative proportion of patients who achieved PASI 75 or PASI 90 during the course of the study (PASI 75: HR 1.39 [95% CI 1.11;1.76]; p-value 0.005; PASI 90: HR 1.46 [95% CI 1.14; 1.86]; p-value 0.002).
  • Overall, secukinumab demonstrates a positive effect compared with ustekinumab.
  • The results also show the same direction of effect, suggesting that secukinumab offers additional benefit compared with ustekinumab.
• Health-related quality of life – Dermatology Life Quality Index (DLQI) responders
  • These showed a statistically significant difference in favour of secukinumab (n=100 [61.7%] vs. n=73 [49.3%]) compared with ustekinumab (RR 1.25 [95% CI 1.02; 1.53]; p-value 0.029).
  • This indicates an additional benefit of secukinumab compared with ustekinumab in terms of health-related quality of life.
• Side effects – severe adverse events (SAEs), discontinuation due to adverse events (AEs), infections and parasitic diseases
  • No statistically significant difference was observed between the treatment groups at week 52 for any of the patient-relevant endpoints: SAE, discontinuation due to AEs, infections and parasitic diseases.
  • This indicates neither greater nor minor harm for secukinumab compared with ustekinumab.
• Conclusion regarding patient population B
  • For the symptom endpoints of pain, pruritus and scaling, there is a consistent effect modification for the criterion of prior treatment with biologics, such that only for patient population B1 (patients with prior treatment with biologics) is there a significant and relevant advantage in favour of secukinumab with regard to the improvement of the symptoms of pruritus, pain and scaling, which results in a non-quantifiable additional benefit.
  • In summary, the assessment of the individual patient-relevant endpoints shows exclusively positive effects; furthermore, there are no disadvantages associated with secukinumab due to adverse events.

b2) Patient population B – Treatment of adult patients with moderate to severe plaque psoriasis who have had an inadequate response to other systemic therapies, including ciclosporin, methotrexate or PUVA (psoralen and ultraviolet A light), or who have a contraindication to or are intolerant of such therapies.– Patient population B 2) Patients without prior treatment with biologics

• There is an indication of a minor additional benefit of secukinumab compared with the appropriate comparator therapy (adalimumab or infliximab or ustekinumab).
• For patient population B2 (without prior treatment with biologics), an additional benefit compared with the appropriate comparator therapy can be inferred on the basis of the positive effects on the morbidity endpoint PASI and health-related quality of life, without any disadvantages in terms of side effects.
• For patients in patient population B2, the effects of secukinumab are therefore assessed, on balance, as a moderate—and not merely minor—improvement in treatment-related benefit compared with the appropriate comparator therapy, within the meaning of Section 2(3), and the extent of the additional benefit is classified as minor.
• mortality
  • For the patient-relevant endpoint of overall mortality, no statistically significant difference was observed between the treatment groups.
  • Consequently, there is no additional benefit of secukinumab compared with ustekinumab; an additional benefit for overall survival is therefore not proven.
• Morbidity – Symptoms (pain)
  • For patients not previously treated with a biologic (patient population B2), however, no statistically significant difference was observed for the endpoints of pruritus and pain; consequently, no additional benefit can be inferred for this patient population.
• Morbidity – Symptoms (itching)
  • For patients not previously treated with a biologic (patient population B2), however, no statistically significant difference was observed for the endpoints of pruritus and pain; consequently, no additional benefit can be inferred for this patient population.
• Morbidity – Symptoms (scaling)
  • For the population without prior treatment with biologics, a statistically significant difference was also observed between the treatment groups (MD −0.57 [95% CI −1.09; −0.06]; p-value 0.296).
  • However, the 95% CI for Hedges’ g did not lie entirely below the irrelevance threshold of −0.2.
  • It cannot therefore be concluded that the effect is clinically relevant.
  • Consequently, no additional benefit for patients without prior treatment with biologics can be inferred for the symptom ‘scaling’ either.
• Morbidity – Remission (PASI 100)
  • No statistically significant difference was observed between the treatment groups in the proportion of patients who achieved PASI 100 at week 52.
  • For the endpoint ‘cumulative proportion of patients who achieved PASI 100 during the course of the study’, a statistically significant difference was observed in favour of secukinumab (based on the Kaplan-Meier estimator) (PASI 100: HR: 1.52 [95% CI 1.14; 2.02]; p-value 0.005).
  • Overall, it is assumed that secukinumab has a positive effect on remission compared with ustekinumab; however, the results are subject to increased uncertainty.
  • From this, an additional benefit of secukinumab over ustekinumab can be inferred.
• Morbidity – Response (PASI 75 and PASI 90)
  • For both response thresholds, PASI 75 and PASI 90, an increase was observed in the proportion of patients achieving a response (PASI 75: RR 1.23 [95% CI 1.08; 1.41]; p-value 0.001; PASI 90: RR 1.28 [95% CI 1.06–1.54]; p-value 0.008) and in terms of the cumulative proportion of patients who achieved PASI 75 or PASI 90 during the course of the study (PASI 75: HR 1.39 [95% CI 1.11;1.76]; p-value 0.005; PASI 90: HR 1.46 [95% CI 1.14; 1.86]; p-value 0.002).
  • Overall, secukinumab demonstrates a positive effect compared with ustekinumab.
  • The results also show the same direction of effect, suggesting that secukinumab offers additional benefit compared with ustekinumab.
• Health-related quality of life – Dermatology Life Quality Index (DLQI) responders
  • These showed a statistically significant difference in favour of secukinumab (n=100 [61.7%] vs. n=73 [49.3%]) compared with ustekinumab (RR 1.25 [95% CI 1.02; 1.53]; p-value 0.029).
  • This indicates an additional benefit of secukinumab compared with ustekinumab in terms of health-related quality of life.
• Side effects – severe adverse events (SAEs), discontinuation due to adverse events (AEs), infections and parasitic diseases
  • No statistically significant difference was observed between the treatment groups at week 52 for any of the patient-relevant endpoints: SAE, discontinuation due to AEs, infections and parasitic diseases.
  • This indicates neither a greater nor a minor risk associated with secukinumab compared with ustekinumab.
• Conclusion regarding patient population B
  • Based on the significant advantages observed for the morbidity endpoints of remission (PASI 100) and response (PASI 75 and PASI 90), which reflect the symptoms of erythema, plaque thickness and scaling, there is also a minor additional benefit from treatment with secukinumab.
  • In summary, the assessment of the individual patient-relevant endpoints shows exclusively positive effects; furthermore, there are no disadvantages associated with secukinumab due to adverse events.

Courtesy translation only, please refer to the German original.