Filgotinib (1) – Jyseleca®

• Clinical trials
  • The benefit assessment is based on the Phase III FINCH1 trial submitted by the pharmaceutical manufacturer. This is a randomised, double-blind trial comparing filgotinib at two doses with adalimumab and placebo, each in combination with MTX.

a1) Adult patients with moderate to severe active rheumatoid arthritis who do not have any unfavourable prognostic factors and who have responded inadequately to, or are intolerant of, previous treatment with a disease-modifying antirheumatic drug (conventional DMARDs, including methotrexate (MTX)) or who have not tolerated such treatment; filgotinib as monotherapy

• For this patient group, the pharmaceutical manufacturer has not submitted any data in the dossier for the assessment of additional benefit.
• For this patient group, the additional benefit of filgotinib as monotherapy compared with the appropriate comparator therapy is not proven.

a2) Adult patients with moderate to severe active rheumatoid arthritis who do not have any unfavourable prognostic factors and who have responded inadequately to or are intolerant of previous treatment with a disease-modifying antirheumatic drug (conventional DMARDs, including methotrexate (MTX)); filgotinib in combination with MTX

• For this patient group, the pharmaceutical manufacturer has not submitted any data in the dossier for the assessment of additional benefit.
• For this patient group, the additional benefit of filgotinib in combination with MTX compared with the appropriate comparator therapy is not proven.

b1) Adult patients with moderate to severe active rheumatoid arthritis for whom first-line treatment with biotechnologically produced DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is indicated; filgotinib as monotherapy

• For this patient group, the pharmaceutical manufacturer has not submitted any data in the dossier for the assessment of additional benefit.
• For this patient group, the additional benefit of filgotinib as monotherapy compared with the appropriate comparator therapy is not proven.

b2) Adult patients with moderate to severe active rheumatoid arthritis for whom first-line treatment with biotechnologically produced DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is indicated; Filgotinib in combination with MTX

• It is assumed that there is a hint of additional benefit.
• mortality
  • At week 52 in the FINCH1 study, there were no statistically significant differences in overall mortality between the two treatment groups.
• Morbidity – Remission (CDAI ≤ 2.8; SDAI ≤ 3.3; Boolean definition according to ACR/EULAR)
  • Remission – assessed using the Clinical Disease Activity Index (CDAI) – is considered to be clinically relevant.
  • At week 52, a statistically significantly higher number of patients achieved remission with filgotinib + MTX compared with treatment with adalimumab + MTX. However, this effect is not confirmed in terms of statistical significance in the sensitivity analyses using alternative substitution strategies.
  • For clinical remission, operationalised as an SDAI ≤ 3.3, there was no statistically significant advantage or disadvantage for filgotinib + MTX compared with adalimumab + MTX at week 52.
  • By contrast, the Boolean definition reveals a statistically significant advantage in favour of filgotinib + MTX.
  • Overall, for the endpoint of remission, the operationalisation using the Boolean definition according to ACR-EULAR at week 52 confirms the statistically significant advantage of filgotinib + MTX over adalimumab + MTX that was observed for the operationalisation as CDAI ≤ 2.8.
  • Overall, therefore, an advantage for filgotinib + MTX over adalimumab + MTX is inferred for the disease remission endpoint.
• Morbidity – Low disease activity (CDAI ≤ 10; SDAI ≤ 11)
  • For the endpoint ‘low disease activity’ (CDAI ≤ 10), the FINCH1 study showed no statistically significant difference overall between the intervention arm (filgotinib + MTX) and the comparator arm (adalimumab + MTX) at week 52.
  • If the additional operationalisation SDAI ≤ 11 is also taken into account, both operationalisations show statistically significant effects of comparable magnitude in favour of filgotinib + MTX compared with adalimumab + MTX at week 52, so that, overall, an advantage for filgotinib + MTX over adalimumab + MTX is inferred for the endpoint ‘low disease activity’.
• Morbidity – Pain (VAS improvement of ≥ 15 mm or points)
  • For this endpoint, the FINCH1 study showed no statistically significant difference between filgotinib + MTX and adalimumab + MTX at week 52 for an improvement of ≥ 15 mm or points.
• Morbidity – Patient-reported assessment of disease activity (VAS improvement of ≥ 15 mm or points)
  • For this endpoint, the FINCH1 study showed no statistically significant difference between filgotinib + MTX and adalimumab + MTX at week 52 for an improvement of ≥ 15 mm or points.
• Morbidity – Physical functional status (improvement in HAQ-DI of ≥ 0.45 points, improvement in HAQ-DI of ≥ 0.22 points)
  • For the patient-relevant endpoint of physical functioning, the FINCH1 study showed no statistically significant difference between the treatment groups in the HAQ-DI at week 52, neither for an improvement of ≥ 0.22 points nor for an improvement of ≥ 0.45 points.
• Morbidity – Fatigue (improvement in FACIT-F of ≥ 7.8 points, improvement in FACIT-F of ≥ 4 points)
  • For the patient-relevant endpoint of fatigue, as measured by the FACIT-F at week 52 in the FINCH1 study, there was no statistically significant difference between the treatment groups for either an improvement of ≥ 4 points or an improvement of ≥ 7.8 points.
• Morbidity – Health status (EQ-5D VAS improvement of ≥ 15 mm or points)
  • In the FINCH1 study at week 52, there was no statistically significant advantage or disadvantage for filgotinib + MTX compared with adalimumab + MTX in terms of health status.
• Health-related quality of life – Health Survey Short Form 36 (SF-36) (improvement in SF-36 of ≥ 5 points)
  • In the FINCH1 study, there was no statistically significant difference between filgotinib + MTX and adalimumab + MTX in the proportion of patients showing an improvement of ≥ 5 points at week 52, neither for the SF-36 physical domain total score nor for the mental domain total score.
• Side effects – severe adverse events (SAEs), discontinuation due to adverse events (AEs)
  • For the endpoints of SAE and discontinuation due to AEs, there were no statistically significant advantages or disadvantages of filgotinib + MTX compared with adalimumab + MTX at week 52 in the FINCH1 study.
• Overall assessment
  • In summary, there was no difference in mortality between the treatment groups at week 52. In the morbidity category, at week 52, statistically significant advantages were observed for filgotinib + MTX compared with adalimumab + MTX in two of the three available operationalisations of remission, including the primary analysis of remission as operationalised by the CDAI. Overall, an advantage for filgotinib + MTX over adalimumab + MTX is inferred for the disease remission endpoint. A statistically significant advantage for filgotinib + MTX over adalimumab + MTX is also observed in terms of low disease activity in one of the two operationalisations considered.
  • For the endpoints relating to joint status, there are effects in favour of filgotinib + MTX compared with adalimumab + MTX; however, these are not clinically relevant. For the other morbidity endpoints – fatigue, physical functioning, pain, health status and patient-reported disease activity – there were no statistically significant differences between filgotinib + MTX and the appropriate comparator therapy, adalimumab + MTX.
  • In the quality of life category, there was no statistically significant difference between the filgotinib + MTX and adalimumab + MTX treatment groups.
  • In the category of side effects, no overall advantages or disadvantages can be identified for filgotinib + MTX compared with adalimumab + MTX at week 52.
  • Overall, at week 52, filgotinib + MTX showed exclusively positive effects compared with adalimumab + MTX, with no associated disadvantages. Although the positive effects of filgotinib + MTX compared with the appropriate comparator therapy in terms of remission and low disease activity are not confirmed in further morbidity endpoints relating to symptoms, nor in quality of life, they are nevertheless assessed overall as a previously unattained, more than minor improvement in treatment-related benefit.

c1) Adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or are intolerant of, prior treatment with one or more bDMARDs and/or tsDMARDs; filgotinib as monotherapy

• For this patient group, the pharmaceutical manufacturer has not submitted any data in the dossier for the assessment of additional benefit.
• For this patient group, the additional benefit of filgotinib as monotherapy compared with the appropriate comparator therapy is not proven.

c2) Adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or are intolerant of, prior treatment with one or more bDMARDs and/or tsDMARDs; filgotinib in combination with MTX

• For this patient group, the pharmaceutical manufacturer has not submitted any data in the dossier for the assessment of additional benefit.
• For this patient group, the additional benefit of filgotinib in combination with MTX compared with the appropriate comparator therapy is not proven.

Courtesy translation only, please refer to the German original.