Tezepelumab (2) – Tezspire®

• Clinical trials
  • Both studies were randomised, double-blind, controlled, multicentre Phase III trials.

Adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP) in whom adequate disease control has not been achieved through treatment with systemic corticosteroids and/or surgery

• For adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP), in whom adequate disease control has not been achieved through treatment with systemic corticosteroids and/or surgical intervention, there is a hint of a non-quantifiable additional benefit for tezepelumab as an add-on therapy to intranasal corticosteroids.
• Overall, the level of certainty of the evidence is a ‘hint’.
• mortality
  • Mortality was recorded in both studies as part of the UEs. In the WAYPOINT study, one death occurred in the placebo arm by week 52.
  • The requirement for certainty of results to carry out an adjusted indirect comparison for the endpoint of mortality has not been met. Consequently, no evaluable data are available for the benefit assessment with regard to the endpoint category of mortality.
• Morbidity – Symptoms (nasal congestion/obstruction, reduction/loss of sense of smell, nasal discharge, postnasal drip, facial pain)
  • For the endpoint of nasal congestion/obstruction, the adjusted indirect comparison shows a statistically significant advantage of tezepelumab + INCS over mepolizumab + INCS.
  • For the endpoint ‘diminished or lost sense of smell’, the adjusted indirect comparison shows a statistically significant advantage of tezepelumab + INCS over mepolizumab + INCS.
  • For the endpoint of nasal discharge, the adjusted indirect comparison shows a statistically significant advantage of tezepelumab + INCS over mepolizumab + INCS.
  • For the endpoint of post-nasal drip, the adjusted indirect comparison shows no statistically significant difference between tezepelumab + INCS and mepolizumab + INCS.
  • For the endpoint of facial pain, the adjusted indirect comparison showed no statistically significant difference between tezepelumab + INCS and mepolizumab + INCS.
• Morbidity – SNOT-22 (22-item Sino-nasal Outcome Test)
  • For the SNOT-22 endpoint, the adjusted indirect comparison showed no statistically significant difference between tezepelumab + INCS and mepolizumab + INCS.
• Morbidity – Impairment of daily activities (assessed using WPAI question 6)
  • However, the requirements for the certainty of results needed to carry out an adjusted indirect comparison for the endpoint ‘impairment of activity’ have not been met. Consequently, no evaluable data are available for this endpoint to allow a comparison of tezepelumab with the appropriate comparator therapy for the purpose of benefit assessment.
• Health-related quality of life
  • For the SF-36, the adjusted indirect comparison shows no statistically significant difference between tezepelumab + INCS and mepolizumab + INCS in the proportion of patients with an improvement in the total score of ≥ 9.4 points (PCS) or ≥ 9.6 points (MCS) (15% of the scale range) by week 52.
• Side effects
  • The requirements for the certainty of results needed to conduct an adjusted indirect comparison for the endpoints of SUEs and discontinuation due to AEs have not been met.
  • Consequently, for the benefit assessment, no evaluable data are available for the endpoint category of side effects that would allow a comparison of tezepelumab with the appropriate comparator therapy.
• Overall assessment
  • For the morbidity endpoint category, a statistically significant advantage in favour of tezepelumab + INCS over mepolizumab + INCS is observed for the endpoints nasal congestion/obstruction, reduction/loss of sense of smell and nasal discharge. For the endpoints of post-nasal drip, facial pain and SNOT-22, there was no statistically significant difference between tezepelumab + INCS and mepolizumab + INCS.
  • For the endpoint category of health-related quality of life, based on the SF-36v2, there was no statistically significant difference between tezepelumab + INCS and mepolizumab + INCS, neither for the physical composite score (PCS) nor the mental health summary score (MCS).
  • Overall, therefore, there are exclusively positive effects for tezepelumab + INCS compared with mepolizumab + INCS. However, the assessment of the morbidity endpoints found to be statistically significant here is based on the use of different assessment tools. The assessment of symptom severity using a 4-point NRS (WAYPOINT) and a VAS (SYNAPSE) allows for assessments of varying levels of detail regarding the respective severity of symptoms; consequently, the magnitude of the demonstrated advantages can only be quantified to a limited extent.
  • Furthermore, based on the adjusted indirect comparison, no evaluable results are available for the endpoint categories of mortality and adverse events. Owing to the non-evaluable results regarding adverse events, it is not possible to conclusively weigh up the advantages demonstrated in the study against potential harms.
  • Overall, therefore, for tezeplumab in adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP), in whom adequate disease control has not been achieved through treatment with systemic corticosteroids and/or surgical intervention, an additional benefit is demonstrated; however, the extent of this advantage cannot be quantified on the basis of the available data.

Courtesy translation only, please refer to the German original.