Using methotrexate to treat erosive hand osteoarthritis

The Methotrexate in ERosive INflammatory Osteoarthritis (MERINO) Trial: A Randomized Placebo-controlled Trial to Investigate Clinical Efficacy and Safety of Methotrexate in Erosive Inflammatory Hand Osteoarthritis.

This study is testing if methotrexate can help people with erosive hand osteoarthritis feel less pain and improve their hand function when other treatments haven't worked.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 163 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Diakonhjemmet Hospital (Academic / other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Oslo)
• Trial ID: NCT04579848 on ClinicalTrials.gov

What this trial studies

This trial is a placebo-controlled randomized controlled trial that investigates the effects of methotrexate on pain, function, and structural outcomes in patients with erosive inflammatory hand osteoarthritis. Participants will be randomly assigned to receive either methotrexate or a placebo for a duration of 52 weeks, with both groups also receiving folic acid. The study aims to determine if methotrexate can provide significant relief for patients who have not responded adequately to other pain relief medications.

Who should consider this trial

Good fit: Ideal candidates are adults with symptomatic erosive inflammatory hand osteoarthritis who have not found relief from other pain medications.

Not a fit: Patients with contraindications to methotrexate or those with abnormal renal function may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve pain management and functional outcomes for patients with erosive hand osteoarthritis.

How similar studies have performed: Other studies have explored methotrexate for inflammatory conditions, but this specific application in erosive hand osteoarthritis is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Finger joint pain 40-80 on 0-100 visual analog scale (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.
* Hand OA according to the American College of Rheumatology (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:

A full list of the exclusion criteria for this study comprised the following:

* Contraindications to methotrexate:

  * Abnormal renal function, defined as serum creatinine \>142 µmol/L in women and \>168 µmol/L in men, or a glomeruli filtration rate (GFR) \<40 mL/min/1.73 m2.
  * Abnormal liver function, defined as transaminases above the upper normal limit, active or previous hepatitis B or C infection, or known cirrhosis
  * Lung fibrosis (maximum 6 months old x-ray), active infection, or reduced hematopoiesis (i.e. anemia, leukopenia and/or thrombocytopenia).
  * Planned pregnancy within 18 months after screening (men/women), and pregnancy, breastfeeding, or insufficient anti-conception therapy for female fertile participants. Contraception should be maintained during treatment and until the end of systemic exposure, i.e. 3 months after methotrexate discontinuation. Sufficient anti-conception therapy consists of intra-uterine device (coil) or hormonal anti-conception (birth control pills, implant, intra-uterine system, dermal patch, vaginal ring, or injections).
  * Alcohol or other drug abuse in the last year.
  * Intolerance to lactose.
* Chronic inflammatory rheumatic diseases (such as rheumatoid arthritis and psoriatic arthritis or gout), active inflammatory bowel disease, or positive rheumatoid factor or anti-CCP antibodies.
* Other severe co-morbidities such as hemochromatosis, fibromyalgia, psoriasis, blood dyscrasias, and coagulation disorders, history of malignancy (except successfully treated squamous or basal cell skin carcinoma), uncontrolled diabetes mellitus, severe hypertension, unstable ischemic heart disease, severe heart failure, severe pulmonary disease, severe and/or opportunistic infections and/or chronic infections, active tuberculosis, positive human immunodeficiency virus (HIV) status, recent stroke, bone marrow hypoplasia, or demyelinating diseases of the central nervous system.
* Other likely causes of hand symptoms: thoracic outlet syndrome, carpal tunnel disease, diabetic cheiropathy, injury in finger joints previous 6 months, or palmar tenosynovitis/trigger finger.
* Oral or intra-muscular steroids in the previous month
* Intra-articular treatments or aspirations of any kind of any joint in the hands 3 months before inclusion
* Analgesics or NSAIDs, unless stable dosage for ≥1 month.
* Symptomatic slow-acting drugs for OA (SYSADOA), unless stable dose for ≥3 months and require stable dose throughout the study.
* Disease-modifying osteoarthritis drugs (DMOADs) previous three months.
* Scheduled hand surgery during study participation.
* Planning to start other treatments for hand OA in the study participation period.
* Not able to adhere to the study visit schedule and protocol requirements.

Where this trial is running

Oslo

• Diakonhjemmet Hospital — Oslo, Norway (Recruiting)

Study contacts

• Study coordinator: Ida K. Haugen, MD, PhD

Conditions Hand Osteoarthritis; Erosive Osteoarthritis