Targeting Synovitis in Hand Osteoarthritis: A Review of Treatment Efficacy and Future Directions

Clinical Question: In patients with hand osteoarthritis (OA), do anti-inflammatory treatments effectively reduce symptoms and modify disease progression?

Bottom Line: Observational studies consistently show synovitis is common in hand OA and linked to both pain and disease progression, suggesting inflammation is a viable treatment target. However, clinical trial results for various anti-inflammatory agents have been conflicting. Prednisolone (10 mg/day) and methotrexate (20 mg/week) have shown the most promise for symptomatic relief in recent trials. Evidence for topical NSAIDs is limited by a scarcity of high-quality placebo-controlled trials, and intra-articular corticosteroids have not demonstrated significant benefits in most hand OA trials, possibly due to methodological limitations such as not requiring baseline synovitis. Biological DMARDs have generally failed to meet primary endpoints. Several ongoing trials, particularly those focusing on intra-articular therapies and methotrexate in patients with inflammatory hand OA, are anticipated to provide further clarity.

Key Findings: Hand osteoarthritis (OA) was historically considered non-inflammatory, but strong evidence now indicates synovial inflammation (synovitis) is common and contributes to pain and disease progression. This review examines the efficacy of various anti-inflammatory treatments for hand OA.

Topical NSAIDs are recommended by international guidelines, but supporting evidence is limited, with only one high-quality placebo-controlled trial showing a small benefit. Oral NSAIDs offer moderate short-term pain relief.

Oral corticosteroids, specifically 10 mg/day of prednisolone (HOPE trial), significantly reduced pain and improved symptoms after six weeks, also showing reductions in ultrasound-defined synovial thickening and MRI-defined bone marrow lesions. However, benefits waned after discontinuation, and long-term use is a concern. Lower doses of prednisolone (5mg) did not show an effect.

Intra-articular corticosteroid injections have generally not shown significant benefits in hand OA trials, particularly for the thumb base (CMC-1) joint, though one study showed improvement in pain on movement in interphalangeal joints. Methodological limitations, such as not requiring baseline synovitis for inclusion and small sample sizes, may have impacted these results.

Among synthetic DMARDs, hydroxychloroquine has not proven effective, even in erosive hand OA. Methotrexate, particularly at 20 mg/week (METHODS trial), demonstrated a statistically significant and clinically relevant pain reduction after six months in patients with synovitis. Earlier studies with lower doses showed non-significant trends.

Biological DMARDs targeting TNF, IL-1, IL-6, and GM-CSF have not met primary efficacy endpoints in hand OA trials and are not recommended. Other anti-inflammatory agents like apremilast, colchicine, and diacerein have also been unsuccessful.

The authors conclude that while synovitis is a promising target, previous trial results are mixed. Prednisolone and methotrexate show potential. They recommend future trials carefully select patients with synovitis, ensure adequate treatment duration, and include long-term follow-up for disease modification. Ongoing trials like PICASSO (intra-articular corticosteroids) and MERINO (methotrexate) are expected to provide important insights.