Bimekizumab (2) – Bimzelx®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted the randomised controlled trial BE OPTIMAL, in which bimekizumab is compared with adalimumab or with a placebo, in either monotherapy or combination therapy.

a) Adults with active psoriatic arthritis who have responded inadequately to, or are intolerant of, previous disease-modifying antirheumatic drug (DMARD) therapy

• For adults with active psoriatic arthritis who have responded inadequately to, or are intolerant of, prior disease-modifying antirheumatic drug (DMARD) therapy, the additional benefit is not proven.
• mortality
  • No deaths occurred in the BE OPTIMAL study.
• Morbidity – Minimal Disease Activity (MDA)
  • For the MDA endpoint, there is no statistically significant difference between bimekizumab and adalimumab.
• Morbidity – Remission (DAPSA ≤ 4)
  • For the endpoint of remission (DAPSA ≤ 4), there was no statistically significant difference between bimekizumab and adalimumab.
• Morbidity – Joints tender on palpation (TJC68 ≤ 1)
  • For the TJC68 endpoint, there was no statistically significant difference between the treatment groups.
• Morbidity – Swollen joints (SJC66 ≤ 1)
  • For the SJC66 endpoint, there was no statistically significant difference between the treatment groups.
• Morbidity – Enthesitis
  • For enthesitis, assessed using the LEI, the mean change at week 52 is used. There is no statistically significant difference between bimekizumab and adalimumab.
  • For enthesitis, assessed using the SPARCC Enthesitis Index, no suitable data are available, as the responder analyses only include patients with a SPARCC score > 0 at baseline, thereby excluding 65.3% of the relevant patient population.
• Morbidity – Axial involvement (BASDAI)
  • For the endpoint of axial involvement (BASDAI), there is no statistically significant difference between bimekizumab and adalimumab.
• Morbidity – Arthritis pain (PtAAP VAS)
  • For the endpoint of arthritis pain (PtAAP VAS), there was no statistically significant difference between bimekizumab and adalimumab.
• Morbidity – Patient-reported global disease activity (PGA-PsA VAS)
  • For the endpoint patient-reported global disease activity (PGA-PsA VAS), there was no statistically significant difference between bimekizumab and adalimumab.
• Morbidity – Disease-related disability (PsAID-12)
  • For the endpoint ‘disease-related disability’ (PsAID-12), there was no statistically significant difference between bimekizumab and adalimumab.
• Morbidity – Health status (EQ-5D VAS)
  • For the health status endpoint (EQ-5D VAS), there was no statistically significant difference between bimekizumab and adalimumab.
• Morbidity – Physical functioning (HAQ-DI)
  • For the physical functioning endpoint (HAQ-DI), the mean change at week 52 is used. There was no statistically significant difference between bimekizumab and adalimumab.
• Morbidity – Fatigue (FACIT-Fatigue)
  • For the endpoint of fatigue (FACIT-Fatigue), there is no statistically significant difference between bimekizumab and adalimumab.
• Morbidity – Skin symptoms (Psoriasis Area and Severity Index (PASI))
  • During the course of the study, this endpoint was assessed exclusively in patients with psoriasis affecting ≥ 3 % of the body surface area at baseline. Only 49% of the relevant patient population were included in the PASI analyses (PASI100, PASI90 and PASI75). This approach by the pharmaceutical manufacturer is inappropriate.
  • Even patients who show no or only minor skin symptoms at the start of the study may develop these symptoms as the disease progresses. Due to the pharmaceutical manufacturer’s chosen operationalisation, it is not possible to draw conclusions for the entire target population.
  • The responder analyses for these endpoints are therefore not suitable for the benefit assessment.
• Morbidity – modified Nail Psoriasis Severity Index (mNAPSI)
  • This endpoint was assessed during the study exclusively in patients who had a score > 0 at the start of the study. 44.7% of the relevant patient population were excluded from the mNAPSI analyses. The responder analyses for this endpoint are therefore – as with the PASI – not suitable for benefit assessment.
• Quality of life – SF-36
  • With regard to health-related quality of life, as assessed using the SF-36, there was no statistically significant difference between bimekizumab and adalimumab for either the mental or physical total scores.
• Quality of life – PsAQoL
  • For health-related quality of life, as assessed by the PsAQoL, there was no statistically significant difference between bimekizumab and adalimumab.
• Side effects – overall rates of SUEs and discontinuation due to AEs
  • For the endpoints of SUEs and discontinuation due to AEs, no statistically significant difference was observed between the treatment groups in either case.
• Side effects – Infections and parasitic diseases (SOC, AE)
  • For the endpoint ‘infections and parasitic diseases’ (SOC, AE), a statistically significant difference was observed between the treatment groups. However, this difference is no more than minor.
• Side effects – fungal infections (HLGT, AE)
  • For the endpoint ‘fungal infections’ (HLGT, AE), there is a statistically significant disadvantage of bimekizumab compared with adalimumab.
• Overall assessment / Conclusion
  • The results for a patient population from the BE OPTIMAL study were presented for adults with active psoriatic arthritis who had an inadequate response to, or were unable to tolerate, prior disease-modifying antirheumatic drug (DMARD) therapy. Bimekizumab was compared with adalimumab.
  • In the endpoint categories of morbidity and health-related quality of life, there was neither an advantage nor a disadvantage for bimekizumab compared with adalimumab. In the endpoint category of side effects, there was no statistically significant difference between the treatment groups for the endpoints of serious side effects (SAEs) and discontinuation due to side effects. In detail, a statistically significant disadvantage of bimekizumab compared with adalimumab was observed for the endpoint of fungal infections. For the endpoint of infections and parasitic diseases, a statistically significant difference was observed between the treatment groups; however, this difference was no more than minor.
  • In the overall conclusion, there are no results available to justify an additional benefit. In contrast, within the ‘adverse effects’ endpoint category, there are specific disadvantages regarding non-serious side effects (fungal infections).
  • Against this background, the G-BA concludes that the additional benefit of bimekizumab over the appropriate comparator therapy is not proven.

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

• For adults with active psoriatic arthritis who have responded inadequately to, or are unable to tolerate, prior treatment with disease-modifying biological anti-rheumatic drugs (bDMARDs), the additional benefit is not proven.
• The pharmaceutical manufacturer has not provided any data for patient population b) to assess the additional benefit of bimekizumab compared with the appropriate comparator therapy, as no relevant study could be identified.

Courtesy translation only, please refer to the German original.