Risankizumab (1) – Skyrizi®

• Clinical trials
  • The M16-178 study was a randomised, open-label, parallel-group trial investigating risankizumab compared with fumaric acid esters in adult patients with moderate to severe plaque psoriasis who had not previously received systemic therapy.
  • The UltIMMa-1 and UltIMMa-2 studies are randomised, double-blind, parallel-group studies with identical protocols (twin studies). These studies investigate risankizumab compared with placebo and ustekinumab in adults with moderate to severe plaque psoriasis.

a) Adult patients with moderate to severe plaque psoriasis who are not eligible for conventional therapy as part of their first-line systemic treatment.

• For adult patients with moderate to severe plaque psoriasis who are not eligible for conventional therapy as part of their first-line systemic treatment, the additional benefit is not proven.
• Overall, therefore, an additional benefit is not proven.
• mortality
  • No deaths occurred in the M16-178 study up to week 24.
• morbidity
  • For the endpoint of remission, as determined by PASI 100, there was a statistically significant advantage in favour of risankizumab compared with fumaric acid esters (RR 9.91 [95% CI 3.20; 30.71]; p-value < 0.001).
  • Similarly, based on the proportion of patients showing an improvement in their PASI score from baseline to week 24 of 75 per cent (PASI 75) or 90 per cent (PASI 90), a statistically significant advantage for risankizumab over fumaric acid esters is evident in each case (PASI 75: RR 1.96 [95 per cent CI 1.51; 2.54]; p-value < 0.001; PASI 90: RR 8.36 [95% CI 3.88; 18.00]; p-value < 0.001).
  • These positive effects are also reflected in patient-reported freedom from symptoms: For the endpoints PSS itch, PSS pain, PSS redness and PSS burning – all measures of patient-reported symptom-free status – a statistically significant advantage in favour of risankizumab over fumaric acid esters was observed in each case.
  • Further advantages in favour of risankizumab were observed in the endpoints ‘absence of scalp lesions (PSSI 0)’, ‘absence of nail lesions (NAPSI 0)’ and patients’ health status as measured by the EQ-5D VAS.
• quality of life
  • Health-related quality of life was assessed in this study using the DLQI and the SF-36. For the DLQI (DLQI 0 or 1), a statistically significant advantage was observed in favour of risankizumab compared with fumaric acid esters.
  • For the SF-36, the physical composite score (PCS) and the mental composite score (MCS) are considered separately. In each case, the mean difference in change from the start of the study to treatment week 24 is taken into account. When examining the mean differences, a statistically significant advantage in favour of risankizumab compared with fumaric acid esters is observed for both the PCS and the MCS. As the confidence interval for Hedges’ g lies entirely outside the irrelevance range [−0.2; 0.2] for both the PCS and the MCS, this is interpreted in each case as a relevant effect.
• Side effects
  • For the endpoints of serious adverse events (SAEs), discontinuation due to adverse events, and infections and parasitic diseases (SOC), no statistically significant difference was observed between the treatment groups in any case.
  • For the specific adverse events involving gastrointestinal disorders (SOC, including the associated PTs diarrhoea, upper abdominal pain, abdominal pain and nausea), vascular disorders (SOC, including the associated PT ‘feeling of heat’) and nervous system disorders (SOC), a statistically significant advantage was observed in each case in favour of risankizumab.

b) Adult patients with moderate to severe plaque psoriasis who have had an inadequate response to, or are intolerant of, systemic therapy.

• For adult patients with moderate to severe plaque psoriasis who have responded inadequately to, or are unable to tolerate, systemic therapy, there is proof of considerable additional benefit for risankizumab compared with the appropriate comparator therapy, ustekinumab.
• Overall, therefore, there is proof of a considerable additional benefit of risankizumab compared with ustekinumab.
• Overall, the certainty of the proof is classified as ‘one level of proof’.
• mortality
  • No deaths occurred in the UltIMMa-1 and UltIMMa-2 studies up to week 52.
• Morbidity – Psoriasis Area and Severity Index (PASI)
  • For the present benefit assessment, the results regarding the proportion of patients with an improvement in their PASI score from baseline to week 52 of 100 per cent (PASI 100), 90 per cent (PASI 90) and 75 per cent (PASI 75) from the start of the study to week 52.
  • At week 52, 64 per cent (UltIMMa-1) and 62 per cent (UltIMMa-2) of patients in the risankizumab arm achieved PASI 100 and thus complete remission; in the ustekinumab arm, by contrast, the figures were only 15 per cent (UltIMMa-1) and 31 per cent (UltIMMa-2).
  • The meta-analysis of both studies shows a statistically significant advantage for risankizumab.
  • A PASI 75 or PASI 90 response is also considered clinically relevant. With regard to the proportion of patients showing an improvement in their PASI score from baseline to week 52 of 75 per cent (PASI 75) or 90 per cent (PASI 90) from baseline to week 52, the meta-analyses of both studies each demonstrate statistically significant advantages for risankizumab over ustekinumab.
• Morbidity – patient-reported symptom-free status – assessed using PSS-itching 0, PSS-pain 0, PSS-redness 0 and PSS-burning 0
  • The meta-analysis for the endpoints PSS-Itch, PSS-Pain, PSS-Redness and PSS-Burning, reflecting patient-reported symptom-free status, shows a statistically significant advantage for risankizumab over ustekinumab in each case.
• Morbidity – freedom from symptoms affecting the fingernails (NAPSI-Finger 0)
  • For the endpoint ‘absence of symptoms on fingernails’ (NAPSI-Finger 0), the meta-analysis of the UltIMMa-1 and UltIMMa-2 studies showed no statistically significant difference between the treatment arms.
• Morbidity – freedom from scalp symptoms (PSSI 0)
  • For the endpoint ‘absence of scalp lesions’ (PSSI 0), the meta-analysis of the UltIMMa-1 and UltIMMa-2 studies showed a statistically significant difference in favour of risankizumab compared with ustekinumab.
• Morbidity – Health status (EQ-5D VAS)
  • For the endpoint ‘health status’ measured using the EQ-5D VAS, the meta-analysis of the UltIMMa-1 and UltIMMa-2 studies showed a statistically significant advantage for risankizumab compared with ustekinumab.
• Quality of life – Dermatology Life Quality Index (DLQI) response
  • For the endpoint of health-related quality of life, as measured by the DLQI, the meta-analysis of the UltIMMa-1 and UltIMMa-2 studies shows a statistically significant advantage in favour of risankizumab compared with ustekinumab.
• Side effects
  • For the patient-relevant endpoint SAE, neither study showed any statistically significant advantage or disadvantage for risankizumab compared with ustekinumab at week 52.
  • For the patient-relevant endpoint ‘discontinuation due to AEs’, neither an advantage nor a disadvantage for risankizumab compared with ustekinumab was observed in either study at week 52.
  • For the endpoint ‘infections and parasitic diseases’, there was no statistically significant difference between the treatment arms in either study at week 52.
• Overall assessment
  • For adult patients with moderate to severe plaque psoriasis who have had an inadequate response to, or are intolerant of, systemic therapy, the endpoint category of morbidity showed a statistically significant advantage in favour of risankizumab over the appropriate comparator therapy, ustekinumab, both in terms of remission as measured by PASI 100 and in terms of an improvement in the PASI score of 75 per cent or 90 per cent at week 52, a statistically significant advantage in favour of risankizumab over the appropriate comparator therapy, ustekinumab.
  • These positive effects are also reflected in patient-reported symptom relief: For the endpoints PSS-itching, PSS-pain, PSS-redness and PSS-burning of patient-reported symptom-free status, a statistically significant advantage in favour of risankizumab over ustekinumab is evident in each case.
  • Further advantages in favour of risankizumab were observed in the endpoints ‘absence of scalp lesions’ and patients’ health status as measured by the EQ-5D VAS.
  • In the health-related quality of life endpoint category, positive effects in favour of treatment with risankizumab over ustekinumab were also observed at week 52, as indicated by a DLQI score of 0 or 1.
  • In the category of side effects, there is neither an advantage nor a disadvantage for risankizumab compared with ustekinumab.
  • Overall, the positive effects of risankizumab on the morbidity endpoints investigated and on health-related quality of life, without any disadvantages in the adverse reaction profile compared with the appropriate comparator therapy, are assessed as a significant improvement in treatment-related benefit not previously achieved, and the extent of the additionalis classified as considerable.

Courtesy translation only, please refer to the German original.