Methotrexate in Erosive Inflammatory Hand Osteoarthritis (MERINO)

Diakonhjemmet Hospital

Status and phase: Enrolling; Phase 4

Conditions: Erosive Osteoarthritis; Hand Osteoarthritis

Treatments: Drug: Folic Acid 1 MG; Drug: Placebo; Drug: Methotrexate Tablets

Study type: Interventional

Funder types: Other

Identifiers

NCT04579848

DIA2020-01

Details and patient eligibility

About

A placebo-controlled randomized controlled trial exploring the effect of methotrexate on pain, function and structural outcomes in erosive inflammatory hand osteoarthritis.

Full description

The trial will include Norwegian adult males and females with symptomatic erosive inflammatory hand osteoarthritis.

Participants will be randomized 1:1 to either:

1. Methotrexate oral x 1/week; weekly starting dose 15 mg for two weeks, followed by 20 mg the remaining weeks (intervention group). Dosage can be reduced to as low as 10 mg if higher doses are not tolerated.
2. Placebo (control group).

Both arms will receive folic acid 1mg daily.

The treatment duration for both groups is 52 weeks.

Enrollment: 163 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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163 participants in 2 patient groups, including a placebo group

Methotrexate

Active Comparator group

Description:

Methotrexate oral x 1/week; weekly starting dose 15 mg for two weeks, followed by 20 mg the remaining weeks. Additional Folic acid 1mg prescribed daily.

Treatment:

Drug: Methotrexate Tablets

Drug: Folic Acid 1 MG

Placebo

Placebo Comparator group

Description:

3 capsules per week for two weeks, followed by 4 capsules the remaining weeks. Additional Folic acid 1mg prescribed daily.

Treatment:

Drug: Placebo

Drug: Folic Acid 1 MG