Methotrexate for Erosive hand osteoarthritis | Hand osteoarthritis

Inclusion criteria

• {"criterion_text":"- Finger joint pain 40-80 on 0-100 VAS with insufficient pain relief from, inability to tolerate or contra-indications to oral paracetamol and/or NSAIDs, and hand symptoms (pain, aching, or stiffness) on most days the previous 6 weeks before randomization.\n- Hand OA according to the ACR criteria, at least 1 distal (DIP) or proximal interphalangeal (PIP) joint of the 2nd-5th finger with radiographic pre-erosive (J-phase) or erosive disease (E-phase) according to the Verbruggen-Veys anatomical phase system, and at least two DIP/PIP joints with power Doppler signal of at least grade 1 or grey-scale synovitis of at least grade 2 on ultrasound."}

Exclusion criteria

• {"criterion_text":"- Contraindications for methotrexate, such as uncontrolled serious comorbidities, active or recurrent infections, malignancy, pregnancy and drug or substance abuse.\n- Other autoimmune or inflammatory rheumatic disease, or psoriasis.\n- Oral or intra-muscular steroids in the previous month.\n- Intra-articular treatments or aspirations of any kind of any joint in the hands 3 months before inclusion.\n- Analgesics, unless stable dosage for ≥1 month.\n- Symptomatic slow-acting drugs for OA (SYSADOA*), unless stable dose for ≥3 months.\n- Disease modifying osteoarthritis drugs (DMOADs**).\n- The complete list of exclusion criteria is provided in the protocol."}

Primary endpoints

• {"endpoint_text":"- Difference in self-reported finger joint pain previous 48 hours on a visual analogue scale (VAS; 0-100 mm) at 6 months (M06) of treatment.","definition_or_measurement_approach":"Self-reported finger joint pain previous 48 hours measured on a visual analogue scale (VAS; 0-100 mm) at month 6 (M06)."}

Secondary endpoints

• {"endpoint_text":"- Fulfillment of Outcome Measures in Rheumatology Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria (all visits).\n- Self-reported finger pain previous 48 hours on a VAS (0-100 mm) (all visits).\n- Self-reported thumb pain previous 48 hours on a VAS (0-100 mm) (all visits).\n- Pain most painful finger joint last 48 hours (VAS) (all visits).\n- Finger pain and thumb base pain (yes/no) on hand diagram (M00, M06).\n- Patient-reported disease activity last 48 hours (VAS) (all visits).\n- Australian/Canadian hand index (AUSCAN) (all visits).\n- Quality-adjusted life years (QALYs) based on the health-related utility scores measured by the generic instrument EQ-5D (all visits).\n- Michigan Hand Outcomes Questionnaire (MHOQ) pain and physical function subscales (M00, M06).\n- Duration of morning stiffness in finger joints (M00, M06)\n- Duration of morning stiffness in thumb base joints (M00, M06)\n- Hospital Anxiety and Depression Scales (HADS) (M00, M06).\n- Pain Catastrophizing Scale (PCS) (M00, M06).\n- Pain Sensitivity Questionnaire (PSQ) (M00, M06).\n- Knee injury and Osteoarthritis Outcome Score (KOOS)-12 (M00, M06).\n- Hip disability and Osteoarthritis Outcome Score (HOOS)-12 (M00, M06).\n- Concomitant medication (all visits).\n- Number of tender and swollen joints (0-30) (all visits).\n- Grip strength (in kg; using a hand dynamometer) (M00, M06, M12).\n- Pain sensitization: Pressure Pain Thresholds (PPT) by digital algometer; temporal summation by punctate probes; Conditioned Pain Modulation (CPM) by blood pressure ischemic test (M00, M06).\n- Ultrasound (screening, all visits): number of finger joints with synovial thickening and power Doppler signals.\n- Conventional radiographs (screening, M06, M12): change in radiographic severity according to: Kellgren-Lawrence scale; Verbruggen-Veys anatomical phase scoring system; OARSI atlas for presence/severity of osteophytes, joint space narrowing and erosions.\n- MRI (M00, M06): structural progression and synovitis on static and dynamic contrast-enhanced MRI sequences.\n- Serum or plasma markers of extracellular matrix turnover, including collagens and aggrecan, and markers of inflammation (M00, M06, M12).\n- Number of adverse events, serious adverse events, and withdrawals because of adverse events (all visits).\n- Change in synovial cellular composition and gene expression with single-cell RNA sequencing analyses; subgroup analyses, n=16 patients (M00, M06).\n- Self-reported knee pain previous 48 hours on a VAS (0-100) (M00, M06).","definition_or_measurement_approach":"As specified per endpoint: many are patient-reported VAS measures (0-100 mm) at specified visits (M00, M06, M12), standardised questionnaires (OMERACT-OARSI responder criteria, AUSCAN, EQ-5D, MHOQ, HADS, PCS, PSQ, KOOS-12, HOOS-12), objective measures (grip strength by dynamometer), imaging assessments (ultrasound, radiographs, MRI) and biomarker assays (serum/plasma markers, single-cell RNA sequencing). Timepoints given where stated."}

Norway

Earliest CTIS Part Ii Submission Date

19-01-2024

Latest Decision Or Authorization Date

22-08-2025

Processing Time Days

581

Number Of Sites

1

Number Of Participants

163

Primary sponsor

Full Name

Diakonhjemmet Sykehus AS

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway