Secukinumab (4) – Cosentyx®

• Clinical trials
  • The renewed benefit assessment of secukinumab was based on the randomised, double-blind Phase III EXCEED trial, in which secukinumab was compared with adalimumab over a period of 52 weeks.

a1) Adult patients with active psoriatic arthritis who have had an inadequate response to, or are intolerant of, prior disease-modifying antirheumatic drug (DMARD) therapy, and who also have moderate to severe plaque psoriasis.

• Overall, there is an indication for a minor additional benefit of secukinumab compared with adalimumab in adult patients with active psoriatic arthritis who have had an inadequate response to, or are intolerant of, prior disease-modifying antirheumatic (DMARD) therapy and who also have moderate to severe plaque psoriasis.
• The effects of secukinumab are therefore assessed as a moderate—rather than merely slight—improvement in treatment-related benefit compared with the appropriate comparator therapy, which has not been achieved to date, and the extent of the additional benefit is classified as minor.
• Overall, an indication is therefore made regarding the certainty of the findings.
• mortality
  • No deaths occurred during the study period in the EXCEED trial.
• Morbidity – Minimal Disease Activity (MDA)
  • For the endpoint of minimal disease activity (MDA), there is no statistically significant difference between the treatment groups.
• Morbidity – Skin symptoms (PASI 100 remission, PASI 90 and PASI 75 response)
  • For the endpoint of skin symptoms assessed using the PASI, a statistically significant advantage in favour of secukinumab compared with adalimumab was observed for both skin symptom remission (PASI 100) and PASI 90 and PASI 75 responses.
  • For the PASI 100 endpoint, an effect modification was observed for the characteristic of age. However, as the observed effect modification cannot be conclusively assessed, it is not taken into account in the evaluation of the additional benefit.
• Morbidity – Physical functional status (HAQ-DI)
  • For the endpoint of physical functional status assessed using the HAQ-DI, there was no major statistically significant difference between the treatment groups, either for the proportion of patients showing an improvement of ≥ 0.45 points (corresponding to 15% of the scale range) nor for the proportion of patients showing an improvement of ≥ 0.35 points.
• Morbidity – Health status (EQ-5D VAS)
  • For the health status endpoint assessed using the EQ-5D VAS, there was no statistically significant difference between the treatment groups.
• Morbidity – Psoriatic arthritis-related pain (pain VAS)
  • For the endpoint ‘psoriatic arthritis-related pain’ assessed using the VAS, no statistically significant difference was observed between the treatment groups.
• Morbidity – Patient-reported global disease activity (PatGA PASDAS VAS)
  • For the endpoint ‘patient-reported global disease activity’ assessed using the PatGA PASDAS VAS, there was no statistically significant difference between the treatment groups.
• Morbidity – Fatigue (FACIT-Fatigue)
  • For the endpoint ‘fatigue’ assessed using the FACIT-Fatigue, there was no major statistically significant difference between the treatment groups, either in the proportion of patients showing an improvement of ≥ 7.8 points (corresponding to 15% of the scale range) nor for the proportion of patients showing an improvement of ≥ 4 points.
• Morbidity – Enthesitis (LEI)
  • For the endpoint of enthesitis, assessed using the LEI, there was no statistically significant difference between the treatment groups in terms of the mean change.
• Morbidity – Dactylitis (LDI)
  • For the endpoint of dactylitis, assessed using the LDI, there was no statistically significant difference in the mean change between the treatment groups.
• Morbidity – Number of joints tender to pressure
  • For the endpoint ‘number of joints tender to pressure’, there was no statistically significant difference between the treatment groups.
• Health-related quality of life – Short Form-36 Health Survey (SF-36)
  • For the health-related quality of life endpoint assessed using the SF-36, the mental health sub-score (MCS) and the physical health sub-score (PCS) are considered separately.
  • No statistically significant advantage was observed either for the proportion of patients with an improvement of ≥ 9.6 points in the MCS or for the proportion of patients with an improvement of ≥ 9.4 points in the PCS.
  • Based on the proportion of patients showing an improvement of ≥ 5 points, a statistically significant advantage in favour of secukinumab compared with adalimumab was observed for the mental health summary score (MCS).
• Side effects – severe adverse events (SUEs) and discontinuation due to adverse events (UEs)
  • For the endpoints of SUEs and discontinuation due to AEs, there was no statistically significant difference between the treatment groups based on all events.
• Overall assessment
  • In the morbidity endpoint category, a statistically significant advantage in favour of secukinumab compared with adalimumab was observed at 52 weeks for the skin symptoms endpoint. No statistically significant differences were observed between the treatment groups for any of the other morbidity endpoints.
  • In the health-related quality of life endpoint category, a statistically significant difference in favour of secukinumab compared with adalimumab was observed in the SF-36 mental health summary score, based on a response threshold of ≥ 5 points. No statistically significant difference was observed between the two treatment arms in the SF-36 physical summary score, in the analyses using a response threshold of 15 per cent, or in the disease-specific quality of life questionnaire (DLQI).
  • In the endpoint category of side effects, there was neither an advantage nor a disadvantage for treatment with secukinumab compared with treatment with adalimumab.
  • Overall, therefore, secukinumab shows a minor positive effect compared with adalimumab in patients with psoriatic arthritis and concomitant moderate to severe plaque psoriasis, in terms of improving skin symptoms. This advantage is also reflected in an improvement in quality of life, as measured by the mental health summary score of the SF-36. No statistically significant differences were observed between the treatment groups in the morbidity endpoints reflecting arthritis symptoms, nor in the side effects.
• Overall view
  • Overall, therefore, a minor additional benefit of secukinumab compared with treatment with adalimumab can be inferred in adult patients with active psoriatic arthritis who have had an inadequate response to, or are intolerant of, previous disease-modifying antirheumatic (DMARD) therapy, and who also have moderate to severe plaque psoriasis.

a2) Adult patients with active psoriatic arthritis who have responded inadequately to, or are intolerant of, prior disease-modifying antirheumatic (DMARD) therapy, without concomitant moderate to severe plaque psoriasis.

• The additional benefit is not proven.
• The pharmaceutical manufacturer has not provided any data for patients without concomitant moderate to severe plaque psoriasis; consequently, no conclusions can be drawn regarding the additional benefit of secukinumab compared with the appropriate comparator therapy.

b) Adult patients with active psoriatic arthritis who have responded inadequately to, or are intolerant of, prior treatment with disease-modifying biological anti-rheumatic drugs (bDMARDs).

• An additional benefit is not proven.
• The pharmaceutical manufacturer has not provided any data for the patient population under assessment; consequently, no conclusions can be drawn regarding the additional benefit of secukinumab compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.