Tofacitinib (5) – Xeljanz®
Rheumatoid arthritis (RA), pretreated patients, monotherapy or combination with methotrexate
Characteristics
| Start date | 01.09.2021 – Marketing authorisation: 22.03.2017 |
|---|---|
| Resolution | 17.02.2022 |
| INN | Tofacitinib |
| Brand name | Xeljanz® |
| Pharm. company | Pfizer Pharma GmbH |
| G-BA Procedure ID | D-723 |
| ATC code | L04AF01 IMMUNOSUPPRESSANTS (L04A) |
| ICD-10 codes (AIS) | M05.00Felty´s syndrome, unspecified site, M05.01Felty´s syndrome, right shoulder, M05.02Felty´s syndrome, right elbow, M05.03Felty´s syndrome, right wrist, M05.04Felty´s syndrome, right hand, M05.05Felty´s syndrome, right hip, M05.06Felty´s syndrome, right knee, M05.07Felty´s syndrome, right ankle and foot, M05.08, M05.10Rheumatoid lung disease with rheumatoid arthritis of unspecified site, M05.11Rheumatoid lung disease with rheumatoid arthritis of right shoulder, M05.12Rheumatoid lung disease with rheumatoid arthritis of right elbow, M05.13Rheumatoid lung disease with rheumatoid arthritis of right wrist, M05.14Rheumatoid lung disease with rheumatoid arthritis of right hand, M05.15Rheumatoid lung disease with rheumatoid arthritis of right hip, M05.16Rheumatoid lung disease with rheumatoid arthritis of right knee, M05.17Rheumatoid lung disease with rheumatoid arthritis of right ankle and foot, M05.18, M05.19Rheumatoid lung disease with rheumatoid arthritis of multiple sites, M05.20Rheumatoid vasculitis with rheumatoid arthritis of unspecified site, M05.21Rheumatoid vasculitis with rheumatoid arthritis of right shoulder, M05.22Rheumatoid vasculitis with rheumatoid arthritis of right elbow, M05.23Rheumatoid vasculitis with rheumatoid arthritis of right wrist, M05.24Rheumatoid vasculitis with rheumatoid arthritis of right hand, M05.25Rheumatoid vasculitis with rheumatoid arthritis of right hip, M05.26Rheumatoid vasculitis with rheumatoid arthritis of right knee, M05.27Rheumatoid vasculitis with rheumatoid arthritis of right ankle and foot, M05.28, M05.29Rheumatoid vasculitis with rheumatoid arthritis of multiple sites, M05.30Rheumatoid heart disease with rheumatoid arthritis of unspecified site, M05.31Rheumatoid heart disease with rheumatoid arthritis of right shoulder, M05.32Rheumatoid heart disease with rheumatoid arthritis of right elbow, M05.33Rheumatoid heart disease with rheumatoid arthritis of right wrist, M05.34Rheumatoid heart disease with rheumatoid arthritis of right hand, M05.35Rheumatoid heart disease with rheumatoid arthritis of right hip, M05.36Rheumatoid heart disease with rheumatoid arthritis of right knee, M05.37Rheumatoid heart disease with rheumatoid arthritis of right ankle and foot, M05.38, M05.39Rheumatoid heart disease with rheumatoid arthritis of multiple sites, M05.80Other rheumatoid arthritis with rheumatoid factor of unspecified site, M05.81Other rheumatoid arthritis with rheumatoid factor of right shoulder, M05.82Other rheumatoid arthritis with rheumatoid factor of right elbow, M05.83Other rheumatoid arthritis with rheumatoid factor of right wrist, M05.84Other rheumatoid arthritis with rheumatoid factor of right hand, M05.85Other rheumatoid arthritis with rheumatoid factor of right hip, M05.86Other rheumatoid arthritis with rheumatoid factor of right knee, M05.87Other rheumatoid arthritis with rheumatoid factor of right ankle and foot, M05.88, M05.89Other rheumatoid arthritis with rheumatoid factor of multiple sites, M05.90, M05.91, M05.92, M05.93, M05.94, M05.95, M05.96, M05.97, M05.98, M05.99, M06.00Rheumatoid arthritis without rheumatoid factor, unspecified site, M06.01Rheumatoid arthritis without rheumatoid factor, right shoulder, M06.02Rheumatoid arthritis without rheumatoid factor, right elbow, M06.03Rheumatoid arthritis without rheumatoid factor, right wrist, M06.04Rheumatoid arthritis without rheumatoid factor, right hand, M06.05Rheumatoid arthritis without rheumatoid factor, right hip, M06.06Rheumatoid arthritis without rheumatoid factor, right knee, M06.07Rheumatoid arthritis without rheumatoid factor, right ankle and foot, M06.08Rheumatoid arthritis without rheumatoid factor, vertebrae, M06.09Rheumatoid arthritis without rheumatoid factor, multiple sites, M06.20Rheumatoid bursitis, unspecified site, M06.21Rheumatoid bursitis, right shoulder, M06.22Rheumatoid bursitis, right elbow, M06.23Rheumatoid bursitis, right wrist, M06.24Rheumatoid bursitis, right hand, M06.25Rheumatoid bursitis, right hip, M06.26Rheumatoid bursitis, right knee, M06.27Rheumatoid bursitis, right ankle and foot, M06.28Rheumatoid bursitis, vertebrae, M06.29Rheumatoid bursitis, multiple sites, M06.30Rheumatoid nodule, unspecified site, M06.40, M06.41, M06.42, M06.43, M06.44, M06.45, M06.46, M06.47, M06.48, M06.49, M06.80Other specified rheumatoid arthritis, unspecified site, M06.81Other specified rheumatoid arthritis, right shoulder, M06.82Other specified rheumatoid arthritis, right elbow, M06.83Other specified rheumatoid arthritis, right wrist, M06.84Other specified rheumatoid arthritis, right hand, M06.85Other specified rheumatoid arthritis, right hip, M06.86Other specified rheumatoid arthritis, right knee, M06.87Other specified rheumatoid arthritis, right ankle and foot, M06.88Other specified rheumatoid arthritis, vertebrae, M06.89Other specified rheumatoid arthritis, multiple sites, M06.90, M06.91, M06.92, M06.93, M06.94, M06.95, M06.96, M06.97, M06.98, M06.99 Show more >> |
| Alpha-ID codes (AIS) | I100729Chronic polyarthritis with systemic involvement n.c, I127708Felty syndrome, I12826Rheumatoid arthritis, I28626Rheumatoid nodules, I6556Seropositive chronic polyarthritis, I6558Chronic polyarthritis with vasculitis, I6559Seronegative chronic polyarthritis, I6561Chronic polyarthritis with bursitis, I68174Rheumatoid bursitis, I73261Rheumatoid polyarthritis, I73371Rheumatoid vasculitis, I79005Inflammatory polyarthritis, I81266Torticollis in chronic polyarthritis |
| DDD | 10 mg O |
| Therapeutic area | Musculoskeletal system diseases Rheumatoid arthritis (RA) |
| Reason for procedure |
Reassessment: §13 (G-BA request)
Original resolution: Tofacitinib (1) (19.10.2017) |
| Therapeutic indication of the resolution |
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Tofacitinib in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs (DMARDs). Tofacitinib can be given as monotherapy in case of intolerance to MTX or when treatment with MTX is inappropriate |
| Subpopulation | Indication | Comparator |
|---|---|---|
| a1) | Adults with moderate-to-severe active rheumatoid arthritis who do not have unfavorable prognostic factors and who have had an inadequate response to or were intolerant of prior treatment with a disease-modifying antirheumatic drug [classic DMARDs, including methotrexate (MTX)] and are eligible for treatment with tofacitinib; tofacitinib in monotherapy in the setting of MTX intolerance or MTX ineligibility. | Alternative classical DMARDs, if appropriate (leflunomide, sulfasalazine) as monotherapy or combination therapy. |
| a2) | Adults with moderate to severe active rheumatoid arthritis who have no unfavorable prognostic factors and who have had an inadequate response to previous previous treatment with a disease-modifying antirheumatic drug [classical DMARDs [classical DMARDs, including methotrexate (MTX)] or have been intolerant of such treatment and are eligible for treatment with tofacitinib; tofacitinib in combination with MTX | Alternative classical DMARDs, if appropriate (MTX, leflunomide, sulfasalazine) as monotherapy or combination therapy. |
| b1) | Adults with moderate to severe active rheumatoid arthritis for whom a initial therapy with biotechnologically manufactured DMARDs (bDMARDs) or DMARDs (tsDMARDs) and who are eligible for treatment with tofacitinib. Tofacitinib treatment; Tofacitinib monotherapy in cases of MTX intolerance or MTX non-suitability | BDMARDs or tsDMARDs (adalimumab or baricitinib or certolizumab pegol or etanercept or sarilumab or tocilizumab or upadacitinib) as monotherapy |
| b2) | Adults with moderate-to-severe active rheumatoid arthritis for whom initial therapy with bioengineered DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is indicated and who are eligible for treatment with tofacitinib; tofacitinib in combination with MTX | BDMARDs or tsDMARDs (abatacept or adalimumab or baricitinib or certolizumab pegol or etanercept or golimumab or infliximab or sarilumab or tocilizumab or upadacitinib) in combination with MTX |
| c1) | Adults with moderate-to-severe active rheumatoid arthritis who have had an inadequate response to, or have been intolerant of, prior treatment with one or more bDMARDs and/or tsDMARDs and are eligible for treatment with tofacitinib; tofacitinib in monotherapy for MTX intolerance or MTX non-suitability. | Change of bDMARD or tsDMARD therapy (adalimumab or baricitinib or certolizumab pegol or etanercept or sarilumab or tocilizumab or upadacitinib as monotherapy) depending on prior therapy |
| c2) | Adults with moderate-to-severe active rheumatoid arthritis who have had an inadequate response to, or have not tolerated, prior treatment with one or more bDMARDs and/or tsDMARDs and are eligible for treatment with tofacitinib; tofacitinib in combination with MTX | Change of bDMARD or tsDMARD therapy (abatacept or adalimumab or baricitinib or certolizumab pegol or etanercept or golimumab or infliximab or sarilumab or tocilizumab or upadacitinib in combination with MTX; or in patients with severe rheumatoid arthritis, rituximab, subject to regulatory approval) depending on prior therapy |
Studies and Results
|
No. of studies
(best subpopulation) |
0 (Data not accepted) |
|---|---|
|
Study design
(best subpopulation) |
Data not accepted (Dossier: no data submitted) |
| Reason for dividing into subpopulations (G-BA) | Number of medications, Previous treatment |
- 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.
Associated procedures
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