TOFA-PREDICT study protocol: a stratification trial to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in psoriatic arthritis (PsA)
Introduction Psoriatic arthritis (PsA) is a chronic, inflammatory, musculoskeletal disease that affects up to 30% of patients with psoriasis. Current challenges in clinical care and research include personalised treatment, understanding the divergence of therapy response and unravelling the multifac...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-10-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/10/e064338.full |
| _version_ | 1811337366580756480 |
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| author | Paco M J Welsing Floris P J G Lafeber Pim A de Jong Janneke Tekstra Marloes W Heijstek Julia Spierings Nienke J Kleinrensink Wouter Foppen Emmerik F A Leijten Sarita A Y Hartgring Mylène P Jansen Juliëtte N Pouw Frank T Perton Nanette L A Vincken Saeed Arbabi |
| author_facet | Paco M J Welsing Floris P J G Lafeber Pim A de Jong Janneke Tekstra Marloes W Heijstek Julia Spierings Nienke J Kleinrensink Wouter Foppen Emmerik F A Leijten Sarita A Y Hartgring Mylène P Jansen Juliëtte N Pouw Frank T Perton Nanette L A Vincken Saeed Arbabi |
| author_sort | Paco M J Welsing |
| collection | DOAJ |
| description | Introduction Psoriatic arthritis (PsA) is a chronic, inflammatory, musculoskeletal disease that affects up to 30% of patients with psoriasis. Current challenges in clinical care and research include personalised treatment, understanding the divergence of therapy response and unravelling the multifactorial pathophysiology of this complex disease. Moreover, there is an urgent clinical need to predict, assess and understand the cellular and molecular pathways underlying the response to disease-modifying antirheumatic drugs (DMARDs). The TOFA-PREDICT clinical trial addresses this need. Our primary objective is to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in PsA.Methods and analysis In this investigator-initiated, phase III, multicentre, open-label, four-arm randomised controlled trial, we plan to integrate clinical, molecular and imaging parameters of 160 patients with PsA. DMARD-naïve patients are randomised to methotrexate or tofacitinib. Additionally, patients who are non-responsive to conventional synthetic (cs)DMARDs continue their current csDMARD and are randomised to etanercept or tofacitinib. This results in four arms each with 40 patients. Patients are followed for 1 year. Treatment response is defined as minimal disease activity at week 16. Clinical data, biosamples and images are collected at baseline, 4 weeks and 16 weeks; at treatment failure (treatment switch) and 52 weeks. For the first 80 patients, we will use a systems medicine approach to assess multiomics biomarkers and develop a prediction model for treatment response. Subsequently, data from the second 80 patients will be used for validation.Ethics and dissemination The study was approved by the Medical Research Ethics Committee in Utrecht, Netherlands, is registered in the European Clinical Trials Database and is carried out in accordance with the Declaration of Helsinki. The study’s progress is monitored by Julius Clinical, a science-driven contract research organisation.Trial registration number EudraCT: 2017-003900-28. |
| first_indexed | 2024-04-13T17:53:51Z |
| format | Article |
| id | doaj.art-f59cdf86a90a459ca0f864f44333af46 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-04-13T17:53:51Z |
| publishDate | 2022-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-f59cdf86a90a459ca0f864f44333af462022-12-22T02:36:35ZengBMJ Publishing GroupBMJ Open2044-60552022-10-01121010.1136/bmjopen-2022-064338TOFA-PREDICT study protocol: a stratification trial to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in psoriatic arthritis (PsA)Paco M J Welsing0Floris P J G Lafeber1Pim A de Jong2Janneke Tekstra3Marloes W Heijstek4Julia Spierings5Nienke J Kleinrensink6Wouter Foppen7Emmerik F A Leijten8Sarita A Y Hartgring9Mylène P Jansen10Juliëtte N Pouw11Frank T Perton12Nanette L A Vincken13Saeed Arbabi14Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsRadiology, UMC Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsRadiology, UMC Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The NetherlandsImage Sciences Institute, University Medical Center Utrecht, Utrecht, The NetherlandsIntroduction Psoriatic arthritis (PsA) is a chronic, inflammatory, musculoskeletal disease that affects up to 30% of patients with psoriasis. Current challenges in clinical care and research include personalised treatment, understanding the divergence of therapy response and unravelling the multifactorial pathophysiology of this complex disease. Moreover, there is an urgent clinical need to predict, assess and understand the cellular and molecular pathways underlying the response to disease-modifying antirheumatic drugs (DMARDs). The TOFA-PREDICT clinical trial addresses this need. Our primary objective is to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in PsA.Methods and analysis In this investigator-initiated, phase III, multicentre, open-label, four-arm randomised controlled trial, we plan to integrate clinical, molecular and imaging parameters of 160 patients with PsA. DMARD-naïve patients are randomised to methotrexate or tofacitinib. Additionally, patients who are non-responsive to conventional synthetic (cs)DMARDs continue their current csDMARD and are randomised to etanercept or tofacitinib. This results in four arms each with 40 patients. Patients are followed for 1 year. Treatment response is defined as minimal disease activity at week 16. Clinical data, biosamples and images are collected at baseline, 4 weeks and 16 weeks; at treatment failure (treatment switch) and 52 weeks. For the first 80 patients, we will use a systems medicine approach to assess multiomics biomarkers and develop a prediction model for treatment response. Subsequently, data from the second 80 patients will be used for validation.Ethics and dissemination The study was approved by the Medical Research Ethics Committee in Utrecht, Netherlands, is registered in the European Clinical Trials Database and is carried out in accordance with the Declaration of Helsinki. The study’s progress is monitored by Julius Clinical, a science-driven contract research organisation.Trial registration number EudraCT: 2017-003900-28.https://bmjopen.bmj.com/content/12/10/e064338.full |
| spellingShingle | Paco M J Welsing Floris P J G Lafeber Pim A de Jong Janneke Tekstra Marloes W Heijstek Julia Spierings Nienke J Kleinrensink Wouter Foppen Emmerik F A Leijten Sarita A Y Hartgring Mylène P Jansen Juliëtte N Pouw Frank T Perton Nanette L A Vincken Saeed Arbabi TOFA-PREDICT study protocol: a stratification trial to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in psoriatic arthritis (PsA) BMJ Open |
| title | TOFA-PREDICT study protocol: a stratification trial to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in psoriatic arthritis (PsA) |
| title_full | TOFA-PREDICT study protocol: a stratification trial to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in psoriatic arthritis (PsA) |
| title_fullStr | TOFA-PREDICT study protocol: a stratification trial to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in psoriatic arthritis (PsA) |
| title_full_unstemmed | TOFA-PREDICT study protocol: a stratification trial to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in psoriatic arthritis (PsA) |
| title_short | TOFA-PREDICT study protocol: a stratification trial to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in psoriatic arthritis (PsA) |
| title_sort | tofa predict study protocol a stratification trial to determine key immunological factors predicting tofacitinib efficacy and drug free remission in psoriatic arthritis psa |
| url | https://bmjopen.bmj.com/content/12/10/e064338.full |
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