Better After CHoosing. Randomly Allocated or Patient Preference Based Treatment With Filgotinib or TNFi in RA (BACH)

Официальное название

Better After CHoosing. Randomly Allocated or Patient Preference Based Treatment With Filgotinib or TNFi in Patients With Active Rheumatoid Arthritis (BACH)

Обзор

Despite their efficacy in the treatment of Rheumatoid Arthritis and their partial advantage over traditional bDMARDs ( biological Disease Modifying antirheumatic drugs), JAK inhibitors (JAKi or tsDMARDs) have not gained preference over Tumor Necrosis Factor inhibitors (TNFi) in guidelines or clinical practice. The biggest influence on recent guidelines has been the "Treat To Target" principle (T2T), in which Shared Decision Making (SDM) plays a key part. Patient preference has proven to be a large barrier in treatment adjustments (14- 37%) while patients showed better adherence and higher treatment satisfaction when engaged in Shared Decision Making. From survey studies it is suggested that patient preference and satisfaction will be in favour of oral JAK inhibitors over parenteral biologics.The investigators want to establish the treatment preference of patients with active RA and compare the treatment satisfaction of patients who are given the opportunity to choose between the JAKi filgotinib and TNFi, to the treatment satisfaction of patients who are randomized to the same treatment options. In addition to higher treatment satisfaction and better adherence, the investigators expect to find an improvement in DAS28-, HAQ-, SQUASH- and WPAI-scores and also an improved activity and work productivity.

Подробное описание

Rationale: Despite their efficacy in the treatment of Rheumatoid Arthritis and their partial advantage over traditional bDMARDs, JAK inhibitors (JAKi or tsDMARDs) have not gained preference over Tumor Necrosis Factor inhibitors (TNFi) in guidelines or clinical practice. The biggest influence on recent guidelines has been the "Treat To Target" principle (T2T), in which Shared Decision Making (SDM) plays a key part. Patient preference has proven to be a large barrier in treatment adjustments (14- 37%) while patients showed better adherence and higher treatment satisfaction when engaged in Shared Decision Making. From survey studies it is suggested that patient preference and satisfaction will be in favour of oral JAK inhibitors over parenteral biologics. The investigators want to establish the treatment preference of patients with active RA and compare the treatment satisfaction of patients who are given the opportunity to choose between the JAKi filgotinib and TNFi, to the treatment satisfaction of patients who are randomized to the same treatment options.

In addition to higher treatment satisfaction and better adherence, the investigators expect to find an improvement in DAS28-, HAQ-, SQUASH- and WPAI-scores and also an improved activity and work productivity.

Objective:

* To evaluate the actual preference of patients when they decide themselves which mode of action they want to use for treatment of rheumatoid arthritis. * To evaluate differences in treatment satisfaction between patients who can choose their therapy and those patients that are randomized for the same treatment options. * To evaluate if adherence to therapy is increased when patients decide their own therapy. * To evaluate the difference in improvement of disease activity by the Disease Activity Score (DAS28) and physical activity as measured by SQUASH questionnaire and fitness trackers.

Study design: This study is a multicenter, randomized, 24-week, open label trial

Study population and intervention:

Early, bDMARD naive RA patients, of whom a group of 50 patients will be given the opportunity to choose between either TNFi (etanercept 50 mg SC once a week or adalimumab 40 mg SC once every two weeks) or filgotinib, an oral JAKi, 200 mg once a day while another group of 50 patients will be randomized to the same treatment arms.

Main study parameters/endpoints: The two primary endpoints consist of:

* The proportion of subjects in the first subgroup choosing filgotinib therapy at baseline * Treatment satisfaction of both subgroups at week 24 at a 5-point Likert scale for current medical treatment.

Burden and risks associated with participation, benefit and group relatedness: All medication is prescribed at the indicated dosages used in clinical care, according to international guidelines. Study burden and risks are similar to daily clinical care: In addition to daily clinical care one half of the participants has to make the treatment choice and all participants will fill in questionnaires, which will take about 15 minutes to complete.

Вмешательства

• Препарат Filgotinib
  200 mg tablet once daily or 100 mg once daily
• Препарат Anti-Tumor Necrosis Factor Alpha Drug (Product)
  Adalimumab subcutaneous injections 40 mg once every two weeks Etanercept subcutaneous injections 50 mg weekly
• Поведенческое 50 patients will have a Free Choice between Filgotinib and anti TNF
  50 patients will be given the opportunity to choose between either TNFi (etanercept 50 mg SC once a week or adalimumab 40 mg SC once every two weeks) or filgotinib, an oral JAKi, 200 mg once a day while another group of 50 patients will be randomized to the same treatment arms.

Первичные конечные точки

• The proportion of subjects in the first subgroup choosing filgotinib therapy at baseline [Срок оценки: Baseline data]
• Treatment satisfaction at week 24 [Срок оценки: 24 weeks]

Вторичные конечные точки (4)

• How patients rate being informed by the neutral information video [Срок оценки: week 6 and week 24]
• How do patients in the treatment Choice group I rate being in control for their treatment decision. [Срок оценки: week 6 and week 24]
• Proportion of subjects who would choose filgotinib (again or otherwise) at 24-weeks if they were allowed to choose again. [Срок оценки: week 24]
• Proportion of patients who were not able to make a treatment decision. [Срок оценки: baseline data]

Критерии участия

Критерии включения

Demographic and general characteristics:

• Adult male or female patients, at least 18 years of age.
• Able and willing to give written informed consent.
• Have sufficient knowledge of the Dutch language to be able to comply with the requirements of the study protocol.

Критерии включения

• Diagnosis of adult-onset RA as defined by the 2010 ACR/ EULAR Rheumatoid arthritis classification criteria;
• Diagnosis of RA for ≥ three months;
• Are being treated ≥ three months with ≥ 1 csDMARD therapy;
• Have had an inadequate response or intolerance to at least 1 csDMARD;
• Have moderately to severely active RA to the discretion of the rheumatologist or defined as a DAS28 ≥ 3.2 at screening and baseline visits;
• Subjects must have been on a stable dose of csDMARD therapy (restricted to methotrexate, chloroquine, hydroxychloroquine, sulfasalazine, or leflunomide) for ≥ 4 weeks prior to the baseline visit.

Критерии исключения

• Previous treatment with any biological DMARD or targeted synthetic DMARD/JAKi;
• Inflammatory rheumatic disease other than RA, except for secondary Sjögren's syndrome.
• Having a contraindication for either TNFi or filgotinib;
• Latent or active tuberculosis;
• Active or recurrent infections;
• History of any malignancy within 5 years except for successfully treated NMSC or localized carcinoma in situ of the cervix;
• ≥ 3x upper limit of normal ALT, AST;
• eGFR ≤ 30 ml/min;
• planned or actual pregnancy or planning to father a child.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• Medical Center Leeuwarden MCL — Leeuwarden

Публикации

• Zak A, Corrigan C, Yu Z, Bitton A, Fraenkel L, Harrold L, Smolen JS, Solomon DH. Barriers to treatment adjustment within a treat to target strategy in rheumatoid arthritis: a secondary analysis of the TRACTION trial. Rheumatology (Oxford). 2018 Nov 1;57(11):1933-1937. doi: 10.1093/rheumatology/key179. PMID 29982720
• Schipper LG, Vermeer M, Kuper HH, Hoekstra MO, Haagsma CJ, Den Broeder AA, van Riel P, Fransen J, van de Laar MA. A tight control treatment strategy aiming for remission in early rheumatoid arthritis is more effective than usual care treatment in daily clinical practice: a study of two cohorts in the Dutch Rheumatoid Arthritis Monitoring registry. Ann Rheum Dis. 2012 Jun;71(6):845-50. doi: 10.1136 PMID 22210852
• Tymms K, Zochling J, Scott J, Bird P, Burnet S, de Jager J, Griffiths H, Nicholls D, Roberts L, Arnold M, Littlejohn G. Barriers to optimal disease control for rheumatoid arthritis patients with moderate and high disease activity. Arthritis Care Res (Hoboken). 2014 Feb;66(2):190-6. doi: 10.1002/acr.22108. PMID 23983001
• Lofland JH, Johnson PT, Ingham MP, Rosemas SC, White JC, Ellis L. Shared decision-making for biologic treatment of autoimmune disease: influence on adherence, persistence, satisfaction, and health care costs. Patient Prefer Adherence. 2017 May 18;11:947-958. doi: 10.2147/PPA.S133222. eCollection 2017. PMID 28572722
• Alten R, Kruger K, Rellecke J, Schiffner-Rohe J, Behmer O, Schiffhorst G, Nolting HD. Examining patient preferences in the treatment of rheumatoid arthritis using a discrete-choice approach. Patient Prefer Adherence. 2016 Nov 1;10:2217-2228. doi: 10.2147/PPA.S117774. eCollection 2016. PMID 27843301
• Schiffner-Rohe J, Alten R, Kruger K, Behmer OS, Schiffhorst G, Rellecke J, Nolting HD. Patient Preferences in the Choice of Disease Modifying Anti-Rheumatic Drugs. Value Health. 2014 Nov;17(7):A385. doi: 10.1016/j.jval.2014.08.2641. Epub 2014 Oct 26. No abstract available. PMID 27200872
• Taylor PC, Betteridge N, Brown TM, Woolcott J, Kivitz AJ, Zerbini C, Whalley D, Olayinka-Amao O, Chen C, Dahl P, Ponce de Leon D, Gruben D, Fallon L. Treatment Mode Preferences in Rheumatoid Arthritis: Moving Toward Shared Decision-Making. Patient Prefer Adherence. 2020 Jan 20;14:119-131. doi: 10.2147/PPA.S220714. eCollection 2020. PMID 32021123
• Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis PMID 16258899

Идентификаторы

NCT: NCT04985435 · RTPO 1111 · NL76371.099.21

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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