Table 2.
Selected clinical trials investigating rheumatoid arthritis prevention.
| Study name | Region, country/Year initiated | Main eligibility criteria | Intervention arm | Control arm | Primary outcome | Notes |
|---|---|---|---|---|---|---|
| Stop Arthritis Very Early (SAVE) | Europe, Mexico, Japan, Austria | Individuals with IA of <16 weeks duration | Methylprednisolone 120 mg IM x1 | Placebo | Drug-free clinical remission at both weeks 12 and 52 | No difference in primary outcome |
| Steroids in Very Early Arthritis (STIVEA) | UK 2002 |
Individuals with IP of 4-10 weeks duration, ACR1958 criteria for probable RA | Methylprednisolone 80mg IM every week x3 | Placebo | DMARD initiation by 6 months | Statistically lower DMARD initiation in methylprednisolone group |
| Dexamethasone in Seropositive Arthralgias | Netherlands 2004 |
Individuals with ACPA- and/or RF-positivity with arthralgia and presence of shared epitope | Dexamethasone 100 mg IM at baseline and 6 weeks | Placebo | 50% reduced antibody or normalization at 6 months | No difference in primary outcome; dexamethasone group had decreased antibody levels |
| Probable Rheumatoid Arthritis: Methotrexate versus Placebo Treatment (PROMPT) | Netherlands 2001 |
Symptoms of arthritis < 2 years duration, undifferentiated arthritis diagnosed using ACR 1958 criteria for probable RA | Methotrexate titrated to maximum of 30 mg PO weekly | Placebo | RA by 1987 ACR criteria | No difference in primary outcome; subgroup of ACPA+ with reduced RA risk |
| Treat Early Arthralgia to Reverse or Limit the Exacerbation of RA (TREAT EARLIER) | Netherlands 2014 |
Clinically suspect arthralgia with onset <1 year, subclinical inflammation of hand or foot joints at 1.5 T MRI | Methylprednisolone 120 mg IM then methotrexate titrated to maximum of 25 mg weekly | Placebo | RA by 2010 ACR/EULAR criteria | Ongoing |
| Definitive Intervention in New Onset Rheumatoid Arthritis (DINORA) | Austria 2007 |
Symptom duration of 2- 12 weeks, synovial swelling present in 2+ joints (at least joint must have been a metacarpophalangeal, proximal interphalangeal, or metatarsophalangeal joint) | Infliximab + methotrexate combination Methotrexate monotherapy |
Placebo | Clinical remission after 1 year | Higher proportion in intervention groups than placebo group |
| Abatacept study to Determine the effectiveness in preventing the development of rheumatoid arthritis in patients with Undifferentiated inflammatory arthritis and to evaluate Safety and Tolerability (ADJUST) |
North America, Europe, South America 2004 |
ACPA-positive patients with UA (not fulfilling the ACR criteria for RA) and synovitis of two or more joints | Abatacept | Placebo | RA by 1987 ACR criteria | Primary outcome not met; suggestion of delay in progression to RA in abatacept group |
| Abatacept Reversing Subclinical Inflammation by MRI in ACPA-positive Arthralgia (ARIAA) | Germany, Czech Republic, Spain 2014 |
ACPA positive, MRI signs of inflammation | Abatacept | Placebo | Improvement in at least one of the MRI inflammation parameters | Preliminary results favor abatacept group (peer review publication pending) |
| Arthritis Prevention in the Preclinical Phase of RA with Abatacept (APIPPRA) |
United Kingdom 2018 |
Individuals with arthralgias, RF and ACPA positivity, or arthralgias with ACPA positive >3x ULN | Abatacept | Placebo | RA by 2010 ACR/EULAR criteria | Ongoing |
| Prevention of Clinically Manifest Rheumatoid Arthritis by B cell Directed therapy in the earliest phase of the disease (PRAIRI) |
Netherlands 2010 |
Individuals with ACPA and RF positivity with arthralgias, never used DMARDs, no IA | Rituximab + Solumedrol | Placebo + Solumedrol | Inflammatory arthritis | No difference in primary outcome; secondary analysis suggested delay in inflammatory arthritis for rituximab group |
| Statins to Prevent Rheumatoid Arthritis (STAPRA) | Netherlands 2015 |
Individuals with arthralgia, ACPA positivity >3x ULN or ACPA and RF, without arthritis | Atorvastatin | Placebo | Clinical arthritis | No difference in primary outcome |
| Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis (StopRA) | USA 2016 |
ACPA >2x ULN, no IA, never used DMARDs | Hydroxychloroquine | Placebo | RA by 2010 ACR/EULAR criteria | Ongoing |
ACPA, anti-citrullinated protein antibodies; ACR, American College of Rheumatology; DMARD, disease-modifying antirheumatic drug; EULAR, European Alliance of Associations for Rheumatology; FDR, first-degree relative; IA, inflammatory arthritis; IM, intramuscular; MRI, magnetic resonance imaging; RA, rheumatoid arthritis; RF, rheumatoid factor; UA, undifferentiated arthritis; ULN, upper limit of normal.