Guselkumab (3) – Tremfya®

• Clinical trials
  • The VEGA trial was a double-blind, three-arm RCT involving adult patients with moderate to severe active ulcerative colitis who were treatment-naïve with regard to TNF-αinhibitors and who had shown intolerance, an inadequate response or a loss of response to conventional therapy with oral or intravenous corticosteroids or immunomodulators (6-mercaptopurine or azathioprine). In the study, the combination therapy of guselkumab plus golimumab was compared with the respective monotherapies of guselkumab and golimumab.

a) Adults with moderate to severe active ulcerative colitis who have responded inadequately to conventional therapy, no longer respond to it, or are intolerant of it

• The additional benefit is not proven.
• mortality
  • No statistically significant difference was observed between the treatment arms for the endpoint ‘all-cause mortality’.
• Morbidity – Symptomatic remission
  • The endpoint ‘symptomatic remission’ is based on two scales of the Mayo score: stool frequency (SF) and rectal bleeding (RB). Both symptoms were recorded by patients in a patient diary over the 7 days prior to the study visit.
  • No statistically significant difference was observed between the treatment arms for the endpoint of symptomatic remission.
• Morbidity – 90-day corticosteroid-free period
  • As part of the commenting procedure, the pharmaceutical manufacturer submitted results for the endpoint ‘90-day corticosteroid-free period’ at week 38.
  • However, the results for the 90-day corticosteroid-free endpoint were presented as a separate analysis without reference to symptomatic remission and are therefore of limited significance.
• Morbidity – Patient Global Impression of Change (PGIC)
  • The PGIC scale consists of a single question, which patients could use to assess the change in their ulcerative colitis symptoms.
  • For the PGIC endpoint, there is a statistically significant advantage of guselkumab over golimumab.
  • However, the magnitude of the advantage demonstrated for the PGIC endpoint is not considered sufficient to justify the conclusion of additional benefit when viewed in the overall context.
• Morbidity – Bowel symptoms (IBDQ)
  • For the ‘intestinal symptoms’ endpoint, assessed using the corresponding IBDQ subscore, no statistically significant difference was observed between the treatment arms.
• Morbidity – Systemic symptoms (IBDQ)
  • For the endpoint ‘systemic symptoms’, assessed using the relevant subscore of the IBDQ, there was no statistically significant difference between the treatment arms.
• Morbidity – Fatigue (PROMIS Fatigue SF 7a)
  • The endpoint ‘fatigue’ was assessed in this study using the ‘PROMIS Fatigue SF 7a’ questionnaire.
  • No statistically significant difference was observed between the treatment arms in the proportion of patients showing a clinically relevant improvement in the PROMIS Fatigue SF 7a of ≥ 8.07 points.
• Morbidity – Hospitalisation
  • The pharmaceutical manufacturer has provided analyses on hospitalisation, admissions to A&E and operations due to ulcerative colitis.
  • However, as no further details are available regarding the operationalisation and the underlying events, these analyses are not used for the present benefit assessment.
  • The endpoint ‘total hospitalisation’ is therefore also not included in the benefit assessment.
• Health-related quality of life – Inflammatory Bowel Disease Questionnaire (IBDQ)
  • The IBDQ is a widely used and validated disease-specific instrument for the indication of ulcerative colitis.
  • With regard to health-related quality of life, as measured by the IBDQ total score, there is no statistically significant difference between the treatment arms.
• Health-related quality of life – Patient-reported Outcome Measurement Information System 29 (PROMIS-29)
  • The PROMIS-29 is a generic questionnaire for the cross-indication assessment of health-related quality of life.
  • For the domains of physical functioning, anxiety, depression, fatigue, pain-related impairment and pain intensity, there was no statistically significant difference between the treatment groups in any case.
  • For the domains of sleep disturbance and participation in social roles and activities, a statistically significant advantage of guselkumab over golimumab was observed in each case.
  • The observed positive effects of guselkumab in these two domains of the PROMIS-29 reflect only partial aspects of health-related quality of life and are therefore considered insufficient in this context to justify the conclusion of additional benefit for the endpoint category of health-related quality of life.
• Side effects – Serious adverse events (SAE)
  • For the SAE endpoint, there is no statistically significant difference between the treatment arms.
• Overall assessment
  • In the mortality category, there is no statistically significant difference between the treatment arms for the endpoint of all-cause mortality.
  • In the morbidity category, there was no statistically significant difference between the treatment arms for the endpoints symptomatic remission, intestinal symptoms (IBDQ), systemic symptoms (IBDQ) and fatigue (PROMIS Fatigue SF 7a). For the PGIC endpoint, guselkumab showed a statistically significant advantage over golimumab. However, the magnitude of the demonstrated advantage in the PGIC endpoint is not considered sufficient to justify the conclusion of an additional benefit when viewed in the overall context.
  • In the category of health-related quality of life, there was no statistically significant difference between the treatment arms for the disease-specific IBDQ. Based on the PROMIS-29, a statistically significant advantage of guselkumab over golimumab is evident for the domains ‘sleep disturbance’ and ‘participation in social roles and activities’. For the domains ‘physical functioning’, ‘anxiety’, ‘depression’, ‘fatigue’, ‘pain-related impairment’ and ‘pain intensity’ of the PROMIS-29, however, no statistically significant difference was observed between the treatment arms. The observed positive effects of guselkumab in these two domains of the PROMIS-29 represent only partial aspects of health-related quality of life. Overall, these effects are considered insufficient in this study to justify the conclusion of additional benefit for the endpoint category of health-related quality of life.
  • In the side effects category, there was no statistically significant difference between the treatment arms in the overall rates of SAEs or discontinuation due to AEs.
  • In the overall assessment of the results, the positive effects demonstrated by guselkumab in the endpoint categories of morbidity (PGIC) and health-related quality of life (the ‘sleep disturbance’ and ‘participation in social roles and activities’ of the PROMIS-29) are not considered sufficient to justify the conclusion of an additional benefit compared with golimumab. An additional benefit is therefore not proven.

b) Adults with moderate to severe active ulcerative colitis who have responded inadequately to a biologic (TNF-α antagonist, integrin inhibitor or interleukin inhibitor), no longer respond to it, or show intolerance

• The additional benefit is not proven.
• For the assessment of the additional benefit of guselkumab in adults with moderate to severe active ulcerative colitis who have responded inadequately to a biologic (TNF-α antagonist, integrin inhibitor or interleukin inhibitor), no longer respond to it or are intolerant of it, the pharmaceutical manufacturer has not submitted any (comparative) studies. As no suitable data are therefore available, additional benefit for patient population b) is not proven.

Courtesy translation only, please refer to the German original.