Methotrexate in Patients with Early Rheumatoid Arthritis

NCT05353829 | Active Not Recruiting Phase 4

• 2 other identifiers: MTXRA2020-000462-41
• Study Type: interventional
• Target: 212
• Locations: 1 country
• Sites: 13

Brief Summary

Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting the small joints of hands and feet, but may also present with systemic, extraarticular features. The Swedish Rheumatology Quality Register (SRQ) is a nationwide quality register with the aim of continuously improving the treatment and follow-up of patients with rheumatic disease. Using this type of quality registers, it is possible to perform a Registrybased Randomised Clinical Trial (R-RCT), that is a randomised clinical trial this is carried out by screening, recruitment and registration of study data is performed based on information given by a quality register. All patients with newly diagnosed RA are included in SRQ. Treatment options for RA include different types of immunosuppression and corticosteroids as bridging therapy. Methotrexate, a synthetic conventional disease modifying antirheumatic drug (csDMARD), which can be given either orally or subcutaneously, is considered a first-line treatment. Studies have shown the beneficial efficacy and improved quality of life for patients with RA treated with methotrexate, however this is not studied in a setting of unselected patients with newly diagnosed RA in northern Sweden. Moreover, it is not known to what extent patients prefer oral or subcutaneous administration route, or if there are any health economic benefits from either of the two administration routes. Further, changes in gut microbiota is not studied in this setting.

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arhtritis; methotrexate; registerbased randomisation; health economics; patient preferences; gut microbiota

Outcome Measures

Primary Outcomes (1)

• Disease activity measured as DAS28 over 12 months

  The primary objective of this study is to study difference in DAS28 (range 0-10, higher value means higher disease activity) over 12 months of follow up in patients with newly diagnosed RA randomized to oral or subcutaneous methotrexate

  12 months

Secondary Outcomes (7)

• Disease activity measured as DAS28 over 24 months

  24 months

• Disease activity measured as DAS28 over 3 months

  3 months

• Disease activity measured as DAS28 over 6 months

  6 months

• Gut microbiota by sequencing of the microbial 16S rRNA gene

  24 months

• Patient preferences

  24 months

Study Arms (2)

Per oral

ACTIVE COMPARATOR

Drug:per oral Methotrexate Tablets dosage 5-30mg once weekly.

Drug: Methotrexate

Subcutaneous

ACTIVE COMPARATOR

Drug: subcutaneous Methotrexate Injection dosage 5-30mg once weekly.

Drug: Methotrexate

Interventions

Methotrexate DRUG

When accepted inclusion the patient will be included in SRQ, and thereafter randomised for Methotrexate per oral or subcutaneous administration

Per oral; Subcutaneous

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has given written consent to participate in the study
• Diagnosis of rheumatoid arthritis by rheumatologist fulfilling 2010
• Rheumatoid Arthritis Classification Criteria
• Indication of methotrexate
• years of age
• Women of Childbearing Capacity (WOCBC) must:
• Comply to use of highly effective contraception methods during the course of the trial.
• Have a negative pregnancy test.
• Male patients included in the study that have fertile female partners must use adequate contraception within their relationship during the same period of time

You may not qualify if:

• Contraindications for methotrexate
• Previous treatment with any DMARD within the last five years
• Known or suspected allergies against methotrexate or any other substance in the given medication
• Anamnestic information on pregnancy, breastfeeding, or planned pregnancy
• Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation or inability to answer questionnaire in written Swedish
• Treatment or disease which, according to the investigator, can affect treatment or study results.
• Fear of needles leading to not being able to use subcutaneous injections
• For the study in gut microbiota: Use of antibiotics or probiotics within the last 3 months

Sponsors & Collaborators

• Region Västerbotten: lead
• Region Gävleborg: collaborator
• Umeå University: collaborator
• Uppsala University: collaborator
• County Council of Norrbotten, Sweden: collaborator
• Vastra Gotaland Region: collaborator
• Västernorrland County Council, Sweden: collaborator
• Dalarna County Council, Sweden: collaborator
• Karolinska University Hospital: collaborator
• Region Jämtland Härjedalen: collaborator
• Sormland County Council, Sweden: collaborator
• Region Stockholm: collaborator

Study Sites (13)

Region Sörmland

Eskilstuna, Sweden

Location

Region Dalarna

Falun, Sweden

Location

Region Gävleborg

Gävle, Sweden

Location

Region Norrbotten

Luleå, Sweden

Location

Reumatologsektionen Örebro universitetssjukhus

Öre, Sweden

Location

Region Jämtland Härjedalen

Östersund, Sweden

Location

Västra Götalandsregionen

Skövde, Sweden

Location

Akademiskt specialistcentrum

Stockholm, Sweden

Location

Danderyds sjukhus

Stockholm, Sweden

Location

Karolinska sjukhuset

Stockholm, Sweden

Location

Region Västernorrland

Sundsvall, Sweden

Location

Region Västerbotten

Umeå, Sweden

Location

Reumatologisk klinik, Västerås

Västerås, Sweden

Location

Related Publications (10)

• Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81. doi: 10.1002/art.27584.

  PMID: 20872595 BACKGROUND

• Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis. 2009 Jul;68(7):1094-9. doi: 10.1136/ard.2008.092668. Epub 2008 Nov 25.

  PMID: 19033290 BACKGROUND

• Schiff M, Weinblatt ME, Valente R, van der Heijde D, Citera G, Elegbe A, Maldonado M, Fleischmann R. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis. 2014 Jan;73(1):86-94. doi: 10.1136/annrheumdis-2013-203843. Epub 2013 Aug 20.

  PMID: 23962455 BACKGROUND

• Bujor AM, Janjua S, LaValley MP, Duran J, Braun J, Felson DT. Comparison of oral versus parenteral methotrexate in the treatment of rheumatoid arthritis: A meta-analysis. PLoS One. 2019 Sep 6;14(9):e0221823. doi: 10.1371/journal.pone.0221823. eCollection 2019.

  PMID: 31490947 BACKGROUND

• Picchianti-Diamanti A, Panebianco C, Salemi S, Sorgi ML, Di Rosa R, Tropea A, Sgrulletti M, Salerno G, Terracciano F, D'Amelio R, Lagana B, Pazienza V. Analysis of Gut Microbiota in Rheumatoid Arthritis Patients: Disease-Related Dysbiosis and Modifications Induced by Etanercept. Int J Mol Sci. 2018 Sep 27;19(10):2938. doi: 10.3390/ijms19102938.

  PMID: 30261687 BACKGROUND

• Sayers E, MacGregor A, Carding SR. Drug-microbiota interactions and treatment response: Relevance to rheumatoid arthritis. AIMS Microbiol. 2018 Oct 26;4(4):642-654. doi: 10.3934/microbiol.2018.4.642. eCollection 2018.

  PMID: 31294239 BACKGROUND

• Schroeder BO, Backhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nat Med. 2016 Oct;22(10):1079-1089. doi: 10.1038/nm.4185. Epub 2016 Oct 6.

  PMID: 27711063 BACKGROUND

• Hsiao B, Fraenkel L. Patient preferences for rheumatoid arthritis treatment. Curr Opin Rheumatol. 2019 May;31(3):256-263. doi: 10.1097/BOR.0000000000000591.

  PMID: 30747733 BACKGROUND

• Durand C, Eldoma M, Marshall DA, Bansback N, Hazlewood GS. Patient Preferences for Disease-modifying Antirheumatic Drug Treatment in Rheumatoid Arthritis: A Systematic Review. J Rheumatol. 2020 Feb;47(2):176-187. doi: 10.3899/jrheum.181165. Epub 2019 Apr 15.

  PMID: 30988125 BACKGROUND

• Striesow F, Brandt A. Preference, satisfaction and usability of subcutaneously administered methotrexate for rheumatoid arthritis or psoriatic arthritis: results of a postmarketing surveillance study with a high-concentration formulation. Ther Adv Musculoskelet Dis. 2012 Feb;4(1):3-9. doi: 10.1177/1759720X11431004.

  PMID: 22870490 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid; Patient Preference

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Patient Satisfaction; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Anna Södergren, MD PhD

  Region Västerbotten

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: April 29, 2022
• Study Start: April 28, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

SE (13)