What is the role of mesalazine in treating rheumatoid arthritis?

Mesalazine Has No Role in Treating Rheumatoid Arthritis

Mesalazine (5-aminosalicylic acid) is not recommended for the treatment of rheumatoid arthritis as it has no established efficacy for this condition and is not included in any current treatment guidelines.

Evidence-Based Treatment Approach for Rheumatoid Arthritis

First-Line Treatment

• Methotrexate is the anchor drug and should be used as first-line therapy for patients with rheumatoid arthritis 1, 2
• Initial dosing should be 15 mg/week orally with folic acid supplementation, optimizing to 20-25 mg/week within the first 3 months 2
• Treatment should begin immediately upon diagnosis to prevent joint damage and disability 1

Alternative First-Line Options (if methotrexate is contraindicated)

1. Leflunomide - similar clinical efficacy to methotrexate in established and recent RA 1, 2
2. Sulfasalazine - considered the third alternative, slightly less effective than leflunomide and methotrexate in the long term 1, 3

Treatment Escalation Algorithm

If inadequate response to methotrexate monotherapy after 3-6 months:

1. For patients without poor prognostic factors:

   • Add or switch to another conventional synthetic DMARD (leflunomide or sulfasalazine) 1
   • Consider triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine 2

2. For patients with poor prognostic factors:

   • Add a biologic DMARD (preferably TNF inhibitor) or JAK inhibitor 1, 2
   • Poor prognostic factors include: high RF/ACPA levels, high disease activity, early joint damage, failure of 2 csDMARDs 1

Why Mesalazine Is Not Used in Rheumatoid Arthritis

While sulfasalazine is an established DMARD for rheumatoid arthritis, mesalazine (which is one component of sulfasalazine) has not demonstrated efficacy in RA treatment. Sulfasalazine is split in the intestine into sulfapyridine and mesalazine, but it remains uncertain whether the parent molecule or the sulfapyridine moiety is the active component for treating RA 3.

Furthermore, mesalazine has been associated with certain serious adverse effects that may outweigh any theoretical benefit:

• Higher rates of interstitial nephritis (11.1 reports per million prescriptions) compared to sulfasalazine (no reports) 4
• Higher rates of pancreatitis (7.5 per million prescriptions) compared to sulfasalazine (1.1 per million prescriptions) 4

Monitoring and Treatment Adjustment

• Disease activity should be monitored every 1-3 months in active disease 1, 2
• If no improvement is seen by 3 months or target (remission or low disease activity) is not reached by 6 months, therapy should be adjusted 1, 2
• Regular monitoring for medication side effects is essential 2

Common Pitfalls to Avoid

1. Delaying treatment initiation - early aggressive treatment is essential for controlling inflammation and preventing joint damage 2
2. Inadequate methotrexate dosing or premature discontinuation 2
3. Insufficient monitoring of disease activity and medication side effects 2
4. Using medications without established efficacy in RA (such as mesalazine) instead of evidence-based treatments

In conclusion, current evidence and guidelines clearly establish methotrexate as first-line therapy for rheumatoid arthritis, with leflunomide and sulfasalazine as alternatives. Mesalazine has no established role in RA treatment and should not be used for this indication.