Secukinumab (3) – Cosentyx®

A) Treatment of adult patients with moderate to severe plaque psoriasis who are suitable for systemic therapy and/or phototherapy

• For the treatment of adult patients with moderate to severe plaque psoriasis who are eligible for systemic therapy, there is an indication for a considerable additional benefit of secukinumab compared with the appropriate comparator therapy, fumaric acid esters.
• 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 compared with the appropriate comparator therapy, are assessed as a significant improvement in treatment-related benefit that has not been achieved to date.
• The extent of the additional benefit is therefore classified as considerable.
• Consequently, an overall indication of the certainty of the findings is derived.
• mortality
  • No deaths occurred in the PRIME study.
• Morbidity – Remission (PASI 100)
  • Remission (PASI 100) is considered to be of clinical relevance.
  • For the time to the occurrence of PASI 100, there was a statistically significant difference in favour of secukinumab compared with fumaric acid esters (HR 25.65 [95% CI 6.17–106.66]; p-value < 0.001).
  • At week 24, 45% of patients in the secukinumab arm achieved PASI 100 and thus complete remission; in the fumaric acid ester arm, by contrast, the figure was only 6%.
• Morbidity – PASI 75 and PASI 90 responses
  • A PASI 75 or PASI 90 response is considered clinically relevant.
  • For both response thresholds (PASI 75 and PASI 90), the median time to achieving a 75% and 90% improvement, respectively, was as follows (PASI 75: HR 9.84 [95% CI 5.51;17.57]; p-value < 0.001; PASI 90: HR 9.75 [95% CI 5.08; 18.72]; p-value < 0.001), a statistically significant difference in favour of secukinumab compared with fumaric acid esters.
  • At week 24, 92% of patients in the secukinumab arm achieved a PASI 75 response compared with 48% of patients in the fumaric acid ester arm.
  • A PASI 90 response was achieved by 76% of patients receiving secukinumab and 31% of patients receiving fumaric acid esters.
• Morbidity – Symptoms of nail involvement (NAPSI 100)
  • A 100 per cent reduction in NAPSI (NAPSI 100), which describes a complete resolution of nail psoriasis, is considered clinically relevant.
  • For the NAPSI 100, there was no statistically significant difference between the treatment groups in patients who had nail involvement at the start of the study.
• Health-related quality of life – Dermatology Life Quality Index (DLQI) response
  • For the time taken to reach a DLQI of 0 or 1, there was a statistically significant difference in favour of secukinumab compared with fumaric acid esters (HR 4.49 [95% CI 2.69–7.47]; p-value < 0.001).
  • Based on the responder analyses of the proportion of patients who achieved a DLQI of 0 or 1 at week 24, the proportion of patients in the secukinumab arm was also higher than in the fumaric acid ester arm (72% vs. 35%).
• Health-related quality of life – Health Survey Short Form 36 (SF-36)
  • With regard to the differences in mean scores, there was no statistically significant difference between the treatment groups.
  • The pharmaceutical manufacturer did not provide sufficient justification for the magnitude of the MIDs used in the responder analyses for the SF-36 (MCS and PCS); consequently, these could not be used for the benefit assessment.
• Side effects – SAE
  • For the patient-relevant endpoint SAE, there is no statistically significant difference between the treatment arms.
• Side effects – Specific AEs
  • For the endpoint ‘infections and parasitic diseases’, there was no statistically significant difference between the treatment arms.
  • For the endpoints ‘blood and lymphatic system disorders’, ‘gastrointestinal disorders’ and ‘feeling of heat’, a statistically significant advantage of secukinumab compared with fumaric acid esters was observed in each case.
• Side effects – Discontinuation due to AEs
  • For the patient-relevant endpoint of discontinuation due to AEs, a statistically significant result was observed in favour of secukinumab compared with fumaric acid esters (2% vs. 40%; RR 0.05 [95% CI 0.01–0.19]; p-value < 0.001).
  • The most common causes for discontinuation of fumaric acid ester therapy were disorders of the blood and lymphatic system (15 per cent in each case; 12 per cent of patients developed lymphopenia) and disorders of the gastrointestinal tract (abdominal pain, upper abdominal pain, diarrhoea).
• Overall assessment
  • For patients with moderate to severe plaque psoriasis who are eligible for systemic therapy, a statistically significant advantage in favour of secukinumab over fumaric acid esters is evident both in the endpoint categories of remission as defined by PASI 100 and in the improvement in the PASI score by 75 per cent or 90 per cent, a statistically significant advantage in favour of secukinumab compared with fumaric acid esters.
  • In the endpoint category of health-related quality of life, there are also substantial effects that provide proof of a clear advantage of secukinumab over fumaric acid esters.
  • During the 24-week study duration, further positive side effects were observed in the category of non-serious/non-severe side effects.
  • For the endpoint ‘discontinuation due to AEs’, there was also minor harm in favour of secukinumab compared with fumaric acid esters.
  • Although the patient-relevant endpoints of pain, itching and scaling—used to assess disease-specific symptoms—were not explicitly recorded, the effects were particularly pronounced for the endpoints of remission (PASI 100) and disease-specific quality of life (DLQI), that the failure to collect data on these symptoms did not result in any reduction in the extent of the additional benefit.

Courtesy translation only, please refer to the German original.