Tofacitinib (5) – Xeljanz®

• Clinical trials
  • The ORAL SURVEILLANCE study was a randomised, open-label, multicentre trial in which tofacitinib at two different doses (5 mg or 10 mg twice daily) in combination with MTX was compared with the TNFα inhibitors adalimumab or etanercept, each in combination with MTX.

a1) Adults 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 are unable to tolerate such treatment, and who are eligible for treatment with tofacitinib; tofacitinib as monotherapy in cases of MTX intolerance or where MTX is unsuitable

• For adults 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 have not tolerated such treatment, and who are eligible for treatment with tofacitinib, the additional benefit of tofacitinib (as monotherapy in cases of MTX intolerance or unsuitability for MTX) there is no proof that it is more effective than the appropriate comparator therapy.
• The dossier did not provide any data for the assessment of the additional benefit of treatment with tofacitinib as monotherapy in cases of MTX intolerance or unsuitability for MTX compared with the appropriate comparator therapy.

a2) Adults 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 have not tolerated it, and who are eligible for treatment with tofacitinib; tofacitinib in combination with MTX

• The dossier did not provide any data for the assessment of the additional benefit of treatment with tofacitinib in combination with MTX compared with the appropriate comparator therapy.

b1) Adults with moderate to severe active rheumatoid arthritis for whom initial treatment with biotechnologically produced DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) and who are eligible for treatment with tofacitinib; tofacitinib as monotherapy in cases of MTX intolerance or when MTX is unsuitable

• For adults with moderate to severe active rheumatoid arthritis for whom first-line therapy with biotechnologically produced DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) and who are eligible for treatment with tofacitinib, the additional benefit of tofacitinib (as monotherapy in cases of MTX intolerance or unsuitability) compared with the appropriate comparator therapy is not proven.
• The dossier did not provide any data for the relevant patient population b1 to assess the additional benefit of treatment with tofacitinib as monotherapy in cases of MTX intolerance or unsuitability for MTX compared with the appropriate comparator therapy.

b2) Adults with moderate to severe active rheumatoid arthritis for whom initial treatment with biotechnologically produced DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) and who are eligible for treatment with tofacitinib; tofacitinib in combination with MTX

• The dossier did not provide any assessable data in the relevant patient population b2 for the evaluation of the additional benefit of treatment with tofacitinib in combination with MTX compared with the appropriate comparator therapy that would be suitable for addressing the question of the renewed benefit assessment.
• The ORAL STRATEGY and ORAL STANDARD studies were the subject of the previous benefit assessment and, without a re-definition of the patient populations compared with the early benefit assessment, are not suitable for assessing the additional benefit in the context of the newre-assessment based on new scientific evidence pursuant to Section 13 of the VerfO.
• As part of the commenting procedure, for those patient populations which, in the view of the pharmaceutical manufacturer and taking into account the new guidelines in the summary of product characteristics (SmPC) as at September 2021, are fully eligible for treatment with tofacitinib, analyses of the ORAL STRATEGY and ORAL STANDARD studies were submitted. However, in the form in which they were presented, these are not suitable for addressing the issues raised by the reassessment, as the requirements of the module templates were not met for the analyses submitted.
• The G-BA initiated the benefit assessment of tofacitinib in March 2021 in light of new scientific findings on rheumatoid arthritis, taking into account the ORAL SURVEILLANCE study.
• In the overall assessment, therefore, the ORAL SURVEILLANCE study is not taken into account for the evaluation of the additional benefit of tofacitinib due to the aspects mentioned.

c1) Adults with moderate to severe active rheumatoid arthritis who have responded inadequately to, or have been unable to tolerate, prior treatment with one or more bDMARDs and/or tsDMARDs, and who are eligible for treatment with tofacitinib; Tofacitinib as monotherapy in cases of MTX intolerance or when MTX is not suitable

• For adults 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 and who are eligible for treatment with tofacitinib, the additional benefit of tofacitinib (as monotherapy in cases of MTX intolerance or unsuitability) compared with the appropriate comparator therapy is not proven.
• The dossier did not provide any data for the assessment of the additional benefit of treatment with tofacitinib as monotherapy in cases of MTX intolerance or unsuitability for MTX, compared with the appropriate comparator therapy.

c2) Adults with moderate to severe active rheumatoid arthritis who have responded inadequately to, or have been unable to tolerate, prior treatment with one or more bDMARDs and/or tsDMARDs and who are eligible for treatment with tofacitinib; Tofacitinib in combination with MTX

• The dossier did not provide any data for the assessment of the additional benefit of treatment with tofacitinib in combination with MTX compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.