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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

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

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: Filgotinib
* Drug: Anti-Tumor Necrosis Factor Alpha Drug (Product)
* Behavioral: 50 patients will have a Free Choice between Filgotinib and anti TNF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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. Inclusion criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 101 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized open label trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Choice group<br>50 patients will be randomized to the choice group, they will view a neutral information video on anti TNF and Filgotinib and will be given the opportunity to choose between these two treatments | Drug: Filgotinib<br>* 200 mg tablet once daily or 100 mg once daily<br>* Other names: Jyseleca;Drug: Anti-Tumor Necrosis Factor Alpha Drug (Product)<br>* Adalimumab subcutaneous injections 40 mg once every two weeks Etanercept subcutaneous injections 50 mg weekly<br>* Other names: Adalimumab (Humira) Etanercept (Enbrel);Behavioral: 50 patients will have a Free Choice between Filgotinib and anti TNF<br>* 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.<br>|
| Active Comparator: Randomization group anti TNF<br>A total of 50 patients will be randomized to the randomization group: 25 of those will start treatment with antiTNF | Drug: Anti-Tumor Necrosis Factor Alpha Drug (Product)<br>* Adalimumab subcutaneous injections 40 mg once every two weeks Etanercept subcutaneous injections 50 mg weekly<br>* Other names: Adalimumab (Humira) Etanercept (Enbrel);|
| Active Comparator: Randomization group Filgotinib<br>A total of 50 patients will be randomized to the randomization group: 25 of those will start treatment with Filgotinib | Drug: Filgotinib<br>* 200 mg tablet once daily or 100 mg once daily<br>* Other names: Jyseleca;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects in the first subgroup choosing filgotinib therapy at baseline | The proportion of subjects in the first subgroup choosing filgotinib therapy at baseline | Baseline data | 
| Treatment satisfaction at week 24 | Treatment satisfaction of both subgroups at week 24 at a 5-point Likert scale for current medical treatment: Ranging from 1: very dissatisfied, 2: dissatisfied, 3: neither dissatisfied nor satisfied, 4: satisfied, 5: very satisfied. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| How patients rate being informed by the neutral information video | How patients rate being informed by the neutral information video on a Likert scale of agreement on being well informed, ranging from 1: strongly disagree, 2: disagree, 3: undecided, 4: agree, 5: strongly agree | week 6 and week 24 | 
| How do patients in the treatment Choice group I rate being in control for their treatment decision. | How do patients in the treatment Choice group I rate being in control for their treatment decision. | 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. | Proportion of subjects who would choose filgotinib (again or otherwise) at 24-weeks if they were allowed to choose again. | week 24 | 
| Proportion of patients who were not able to make a treatment decision. | Proportion of patients who were not able to make a treatment decision. | baseline data |