Inebilizumab (2) – Uplizna®

• Clinical trials
  • The pharmaceutical manufacturer has submitted the MITIGATE study for the assessment of the additional benefit of inebilizumab compared with the appropriate comparator therapy.
  • The study is a double-blind, randomised, controlled trial comparing treatment with inebilizumab against placebo in adults with active IgG4-related disease (IgG4-RD) over a period of 52 weeks.

Adults with active immunoglobulin G4-related disease (IgG4-RD)

• Hint for a non-quantifiable additional benefit.
• Overall, a statistically significant advantage of inebilizumab over placebo is evident for the endpoint of IgG4-RD flares. However, as it remains unclear what effects the prevention of relapses by inebilizumab has on the long-term course of the disease and on subsequent complications, compared with the treatment of relapses with glucocorticoids, the extent of the demonstrated advantage is non-quantifiable.
• The strength of the evidence is classified as ‘a hint’. Despite an overall low potential for bias across endpoints, there are uncertainties regarding the interpretability of the results for the endpoint ‘IgG4-RD relapses’ and due to the glucocorticoid tapering phase being shorter than that recommended in the guidelines.
• Overall, this therefore provides a hint of a non-quantifiable additional benefit for inebilizumab in adults with active IgG4-RD.
• mortality
  • Overall mortality
  • No deaths occurred in either treatment arm of the MITIGATE trial.
• Morbidity – IgG4-RD flares
  • For the endpoint ‘IgG4-RD relapses’, the pharmaceutical manufacturer provides analyses of the time to the first treated IgG4-RD relapse confirmed by an independent, blinded decision-making panel.
  • Overall, a statistically significant advantage of ineibilizumab over placebo was observed for the endpoint of IgG4-RD relapses. However, it remains unclear whether, and to what extent, the observed effects of inebilizumab in preventing relapses, compared with the treatment of relapses that have occurred with glucocorticoids in the control arm, lead to an improvement in long-term disease progression and to the prevention of secondary complications.
• Morbidity – Symptoms (Patient Global Assessment of Disease Activity (PGA))
  • For the endpoint ‘symptoms’, assessed using the PGA, there was no statistically significant difference between the treatment arms.
• Morbidity – Fatigue (Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-Fatigue))
  • The ‘Functional Assessment of Chronic Illness Therapy – Fatigue Scale’ (FACIT-Fatigue) is a fatigue-specific module of the ‘Functional Assessment of Chronic Illness Therapy Measurement System’ (FACIT).
  • For the endpoint of fatigue, assessed using the FACIT-Fatigue, there is no statistically significant difference between the treatment arms.
• Health-related quality of life
  • Health-related quality of life was assessed using the SF-36v2. For the SF-36, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) are considered separately.
  • No statistically significant difference was observed between the treatment arms for health-related quality of life, as assessed by the SF-36v2.
• Side effects – severe adverse events (SUEs), severe adverse events (UEs) and discontinuation due to UEs
  • For the endpoints SUEs, severe AEs and discontinuation due to AEs, there was no statistically significant difference between the treatment arms in any case.
• Side effects – Infections and parasitic diseases (SUEs) and disorders of the blood and lymphatic system (severe UEs)
  • In detail, for the endpoints infections and parasitic diseases (SUEs) and disorders of the blood and lymphatic system (severe AEs), there was a statistically significant disadvantage of inebilizumab compared with placebo in each case.
• Overall view
  • Overall, there is an advantage of inebilizumab compared with placebo for the endpoint of IgG4-RD relapses. However, as it remains unclear what effects the prevention of flare-ups by inebilizumab, compared with the treatment of flare-ups with glucocorticoids, has on the long-term course of the disease and on subsequent complications, the extent of the demonstrated advantage is non-quantifiable. Furthermore, no advantages are observed in other morbidity endpoints and health-related quality of life considered in the benefit assessment.
  • Overall, therefore, inebilizumab provides additional benefit for adults with active IgG4-RD, the extent of which cannot be quantified on the basis of the available data.

Courtesy translation only, please refer to the German original.