Tofacitinib (3) – Xeljanz®

• Clinical trials
  • The benefit assessment is based on the randomised, double-blind, actively controlled OPAL BROADEN trial submitted by the pharmaceutical manufacturer.

a) Adult patients with active psoriatic arthritis who have responded inadequately to, or have been unable to tolerate, previous disease-modifying antirheumatic drug (DMARD) therapy.

• For adult patients with active psoriatic arthritis who have responded inadequately to, or are unable to tolerate, prior disease-modifying antirheumatic (DMARD) therapy or have been unable to tolerate it, there is a hint of a minor additional benefit compared with the appropriate comparator therapy, adalimumab.
• Overall, there is a hint of a minor additional benefit of tofacitinib compared with adalimumab.
• mortality
  • No deaths occurred in the relevant patient population during the study period.
• Morbidity – Minimal Disease Activity (MDA)
  • For the endpoint of minimal disease activity (MDA) as assessed by the MDA score, there is no statistically significant difference between the treatment groups.
• Morbidity – Physical functional status (HAQ-DI)
  • For the endpoint of physical functional status assessed using the HAQ-DI, there was no statistically significant difference between the treatment groups.
• Morbidity – Enthesitis (LEI)
  • For the endpoint of enthesitis, as assessed using the LEI, there was no statistically significant difference between the treatment groups.
• Morbidity – Dactylitis (DSS)
  • For the endpoint of dactylitis, assessed using the DSS, there was no statistically significant difference between the treatment groups.
• Morbidity – Itching (ISI NRS)
  • For the endpoint of pruritus assessed using the ISI NRS, there was no statistically significant difference between the treatment groups.
• Morbidity – Arthritis-related pain (PAAP VAS)
  • For the endpoint of arthritis-related pain assessed using a VAS, there was no statistically significant difference between the treatment groups.
• Morbidity – Patient-reported global disease activity (Psoriatic Arthritis VAS)
  • For the endpoint of patient-reported global disease activity, assessed using a VAS, there was no statistically significant difference between the treatment groups.
• Morbidity – Fatigue (FACIT-Fatigue)
  • For the endpoint of fatigue assessed using the FACIT-Fatigue, there was no statistically significant difference between the treatment groups.
• Morbidity – Ankylosing spondylitis disease activity (BASDAI)
  • For the endpoint of ankylosing spondylitis disease activity, as assessed using the BASDAI, there was no statistically significant difference between the treatment groups.
• Morbidity – Number of joints tender on palpation
  • For the endpoint ‘number of joints tender to pressure’ based on 68 joints, a statistically significant difference in favour of tofacitinib was observed in terms of the change from the start of the study to month 12. Based on the mean difference, an improvement of 3.3 joints was observed compared with the adalimumab arm (MD –3.33 [95% CI –6.42; –0.25]; p-value = 0.034).
• Morbidity – number of swollen joints
  • For the endpoint ‘number of swollen joints’ based on 66 joints, a statistically significant difference in favour of tofacitinib was observed in the change from the start of the study to month 12. Based on the mean difference, an improvement of 2 joints was achieved compared with the adalimumab arm (MD −1.96 [95% CI −3.43; −0.50]; p-value = 0.009).
  • Furthermore, there is an effect modification for this endpoint based on the characteristic of disease activity at the start of the study. Whilst a statistically significant advantage in favour of tofacitinib was observed for patients with high disease activity (PASDAS ≥ 5.4) (mean difference between the treatment groups of 4.9 joints), there was no statistically significant difference between the treatment groups for patients without high disease activity (PASDAS < 5.4).
  • At the time of enrolment in the study, patients with high disease activity had an average of 14.5 (tofacitinib arm) and 11.5 (adalimumab arm) swollen joints, respectively. Under treatment with tofacitinib, patients achieved an average improvement of 12.2 joints, whilst under treatment with adalimumab they achieved an average improvement of 7.4 joints. As the number of joints showing therapeutic improvement following treatment with tofacitinib was thus higher than the baseline value for patients in the adalimumab arm, it was not possible to demonstrate a comparable absolute improvement in the control arm compared with the active treatment arm.
• Morbidity – Health status (EQ-5D VAS)
  • For the health status endpoint assessed using the EQ-5D VAS, a statistically significant difference was observed in favour of tofacitinib (MD 6.79 [95% CI 0.57; 13.01]; p-value = 0.033).
  • Hedges’ g is used to assess the relevance of the result. The 95% confidence interval does not lie entirely above the irrelevance threshold of 0.2. It cannot therefore be concluded that the effect is clinically relevant (Hedges’ g: 0.33 [95% CI 0.00; 0.65]; p-value = 0.048).
• Quality of life – Dermatology Life Quality Index (DLQI)
  • No statistically significant difference was found between the treatment groups for the DLQI.
• Side effects – SAE and discontinuation due to AE
  • For the endpoints SAE and discontinuation due to AEs, there is no statistically significant difference between the treatment groups in either case.
• Overall assessment
  • The benefit assessment was based on the randomised, double-blind, active-controlled OPAL BROADEN trial, in which tofacitinib was compared with adalimumab.
  • For tofacitinib, statistically significant advantages were observed in the morbidity endpoints of the number of tender and swollen joints, although an advantage in swollen joints was only observed in patients with high disease activity (PASDAS ≥ 5.4).
  • However, no statistically significant differences between the treatment groups were observed in any of the other morbidity endpoints assessed (disease activity, physical functional status, enthesitis, dactylitis, pruritus, arthritis-related pain, fatigue and health status) or in the endpoint categories of health-related quality of life and side effects.
  • The statistically significant effects in favour of tofacitinib in the endpoints relating to the number of tender and swollen joints are classified as minor in extent. On balance, the effects of tofacitinib are therefore assessed as a moderate—and not merely minor—improvement in treatment-related benefit, as defined in Section 2(3), which has not yet been achieved compared with the appropriate comparator therapy, and the extent of the additional benefit is classified as minor.

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

• For adult patients with active psoriatic arthritis who have responded inadequately to, or are intolerant of, 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 this patient population; consequently, no conclusions can be drawn regarding the additional benefit of tofacitinib compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.