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

Rheumatoid Arthritis Clinical Trial

— BACH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04985435
• Other study ID #: RTPO 1111
• Secondary ID: NL76371.099.21
• Status: Recruiting
• Phase: Phase 4
• Start date: May 12, 2021
• Est. completion date: April 2023

Study information

• Verified date: July 2021
• Source: Rheumatology Research Center Northern Netherlands
• Contact: Reinhard Bos, MD PhD
• Phone: 0031(0)582866104
• Email: r.bos[@]mcl.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: April 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 101 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Filgotinib
200 mg tablet once daily or 100 mg once daily
• Anti-Tumor Necrosis Factor Alpha Drug (Product)
Adalimumab subcutaneous injections 40 mg once every two weeks Etanercept subcutaneous injections 50 mg weekly

Behavioral:
• 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.

Locations

Country	Name	City	State
Netherlands	Medical Center Leeuwarden MCL	Leeuwarden

Sponsors (4)

Lead Sponsor	Collaborator
R.Bos	Galapagos NV, Leiden University Medical Center, Medical Centre Leeuwarden

Country where clinical trial is conducted

Netherlands, 

References & Publications (22)

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Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Kerstens PJ, Nielen MM, Vos K, van Schaardenburg D, Speyer I, Seys PE, Breedveld FC, Allaart CF, Dijkmans BA. DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis. Ann Rheum Dis. 2010 Jan;69(1):65-9. doi: 10.1136/ard.2008.097683. — View Citation

Lee YH, Song GG. Relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison to adalimumab in patients with active rheumatoid arthritis. Z Rheumatol. 2020 Oct;79(8):785-796. doi: 10.1007/s00393-020-00750-1. — View Citation

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Louder AM, Singh A, Saverno K, Cappelleri JC, Aten AJ, Koenig AS, Pasquale MK. Patient Preferences Regarding Rheumatoid Arthritis Therapies: A Conjoint Analysis. Am Health Drug Benefits. 2016 Apr;9(2):84-93. — View Citation

Mattukat K, Boehm P, Raberger K, Schaefer C, Keyszer G, Mau W. How Much Information and Participation Do Patients with Inflammatory Rheumatic Diseases Prefer in Interaction with Physicians? Results of a Participatory Research Project. Patient Prefer Adherence. 2019 Dec 17;13:2145-2158. doi: 10.2147/PPA.S209346. eCollection 2019. — View Citation

Nota I, Drossaert CH, Taal E, van de Laar MA. Arthritis patients' motives for (not) wanting to be involved in medical decision-making and the factors that hinder or promote patient involvement. Clin Rheumatol. 2016 May;35(5):1225-35. doi: 10.1007/s10067-014-2820-y. Epub 2014 Nov 14. — View Citation

Raghunath S, Hijjawi R, Hoon E, Shanahan EM, Goldblatt F. Qualitative assessment of medication adherence in patients with rheumatic diseases on biologic therapy. Clin Rheumatol. 2019 Oct;38(10):2699-2707. doi: 10.1007/s10067-019-04609-y. Epub 2019 Jun 6. — View Citation

Schiffner-Rohe J, Alten R, Krüger 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. — View Citation

Schildmann J, Grunke M, Kalden JR, Vollmann J. Information and participation in decision-making about treatment: a qualitative study of the perceptions and preferences of patients with rheumatoid arthritis. J Med Ethics. 2008 Nov;34(11):775-9. doi: 10.1136/jme.2007.023705. — View Citation

Schipper LG, van Hulst LT, Grol R, van Riel PL, Hulscher ME, Fransen J. Meta-analysis of tight control strategies in rheumatoid arthritis: protocolized treatment has additional value with respect to the clinical outcome. Rheumatology (Oxford). 2010 Nov;49(11):2154-64. doi: 10.1093/rheumatology/keq195. Epub 2010 Jul 29. — View Citation

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/annrheumdis-2011-200274. Epub 2011 Dec 30. — View Citation

Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P, Kvien TK, Navarro-Compán MV, Oliver S, Schoels M, Scholte-Voshaar M, Stamm T, Stoffer M, Takeuchi T, Aletaha D, Andreu JL, Aringer M, Bergman M, Betteridge N, Bijlsma H, Burkhardt H, Cardiel M, Combe B, Durez P, Fonseca JE, Gibofsky A, Gomez-Reino JJ, Graninger W, Hannonen P, Haraoui B, Kouloumas M, Landewe R, Martin-Mola E, Nash P, Ostergaard M, Östör A, Richards P, Sokka-Isler T, Thorne C, Tzioufas AG, van Vollenhoven R, de Wit M, van der Heijde D. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016 Jan;75(1):3-15. doi: 10.1136/annrheumdis-2015-207524. Epub 2015 May 12. Review. — View Citation

Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, McInnes IB, Sepriano A, van Vollenhoven RF, de Wit M, Aletaha D, Aringer M, Askling J, Balsa A, Boers M, den Broeder AA, Buch MH, Buttgereit F, Caporali R, Cardiel MH, De Cock D, Codreanu C, Cutolo M, Edwards CJ, van Eijk-Hustings Y, Emery P, Finckh A, Gossec L, Gottenberg JE, Hetland ML, Huizinga TWJ, Koloumas M, Li Z, Mariette X, Müller-Ladner U, Mysler EF, da Silva JAP, Poór G, Pope JE, Rubbert-Roth A, Ruyssen-Witrand A, Saag KG, Strangfeld A, Takeuchi T, Voshaar M, Westhovens R, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):685-699. doi: 10.1136/annrheumdis-2019-216655. Epub 2020 Jan 22. — View Citation

Stalpers J. Psychological Determinants of Subjective health. Doctoral dissertation, Nyenrode Business Universiteit, The Netherlands. Nyenrode Business Universiteit. Doctoral dissertation, Nyenrode Business Universiteit, The Netherlands 2009;.

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. — View Citation

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. — View Citation

van Eijk IC, Nielen MM, van der Horst-Bruinsma I, Tijhuis GJ, Boers M, Dijkmans BA, van Schaardenburg D. Aggressive therapy in patients with early arthritis results in similar outcome compared with conventional care: the STREAM randomized trial. Rheumatology (Oxford). 2012 Apr;51(4):686-94. doi: 10.1093/rheumatology/ker355. Epub 2011 Dec 13. — View Citation

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. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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