From the Guidelines
Leflunomide 20 mg daily is more appropriate than nabumetone (Relafen DS) for a rheumatoid arthritis patient already on abatacept (Orencia) who has experienced GI upset with meloxicam and ibuprofen. This recommendation is based on the most recent and highest quality evidence from the 2020 EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs 1. Leflunomide is a disease-modifying antirheumatic drug (DMARD) that addresses the underlying autoimmune process in rheumatoid arthritis by inhibiting pyrimidine synthesis, whereas nabumetone is simply another NSAID that would likely cause similar GI issues as meloxicam and ibuprofen. When starting leflunomide, patients typically begin with a loading dose of 100 mg daily for 3 days, followed by the maintenance dose of 20 mg daily. Patients should be monitored for potential side effects including elevated liver enzymes, hair loss, and blood pressure changes. Regular blood tests (CBC, liver function) are recommended every 2-4 weeks initially, then every 1-3 months once stable. Leflunomide works synergistically with abatacept to control disease activity through different mechanisms - abatacept blocks T-cell activation while leflunomide inhibits rapidly dividing inflammatory cells, providing more comprehensive disease control than simply adding another NSAID to the regimen. The EULAR recommendations emphasize the importance of using DMARDs, such as leflunomide, as part of the treatment strategy for rheumatoid arthritis, especially in patients who have contraindications or intolerance to other DMARDs like methotrexate 1. In this case, the patient's GI upset with meloxicam and ibuprofen suggests that adding another NSAID like nabumetone may not be the best option, and instead, adding a DMARD like leflunomide could provide better disease control and improve the patient's quality of life. It is also worth noting that the patient's inflammatory markers are trending down, which suggests that the current treatment with Orencia is having some effect, and adding leflunomide could help to further reduce disease activity and improve symptoms. Overall, the evidence suggests that adding leflunomide 20 mg daily is a more appropriate option than adding nabumetone (Relafen DS) for this patient.
From the FDA Drug Label
The ACR20 Responder at Endpoint rates are shown in Figure 1. Leflunomide was statistically significantly superior to placebo in reducing the signs and symptoms of RA by the primary efficacy analysis, ACR20 Responder at Endpoint, in study US301 (at the primary 12 months endpoint) and MN301 (at 6 month endpoint) ACR20 Responder at Endpoint rates with leflunomide treatment were consistent across the 6 and 12 month studies (41 to 49%).
Leflunomide Efficacy: Leflunomide has been shown to be effective in reducing the signs and symptoms of rheumatoid arthritis (RA) in clinical trials, with ACR20 Responder at Endpoint rates ranging from 41 to 49% in 6 and 12 month studies.
- Key Benefits:
- Reduction of signs and symptoms of RA
- Inhibition of structural damage
- Improvement in physical function
- Key Considerations:
- Potential for hepatotoxicity, particularly in patients with pre-existing liver disease
- Need for regular monitoring of liver enzymes and blood cell counts
- Potential for increased risk of malignancy, particularly lymphoproliferative disorders
- Contraindicated in pregnancy and women of childbearing potential must use reliable contraception Given the patient's history of GI upset with meloxicam and ibuprofen, and considering the potential benefits and risks of leflunomide, adding leflunomide 20 mg daily may be a suitable option for this patient, as it has been shown to be effective in reducing the signs and symptoms of RA and has a different mechanism of action compared to NSAIDs like meloxicam and ibuprofen. However, close monitoring of liver enzymes and blood cell counts is necessary to minimize the risk of hepatotoxicity and other adverse effects. 2 2 2
From the Research
Patient's Current Condition
The patient is a rheumatoid arthritis patient currently on Orencia 125 mg weekly injections. She reports joint pain in her neck, lower back, hands, and knees, as well as chronic swelling in her hands that is worsening. However, no swelling was noted on exam, and her inflammatory markers are trending down.
Treatment Options
The patient cannot tolerate meloxicam or ibuprofen due to GI upset. Two potential treatment options are being considered:
- Adding leflunomide 20 mg daily
- Adding Relafen DS (nabumetone), an NSAID known to be less harsh on the stomach
Efficacy of Leflunomide
Studies have shown that leflunomide is effective in treating rheumatoid arthritis. According to 3, leflunomide significantly improved the signs and symptoms of RA, with a 41%-64% improvement by ACR 20 responder criteria. Additionally, 4 found that leflunomide improved all clinical outcomes and delayed radiologic progression at both 6 and 12 months of treatment compared to placebo.
Comparison to Methotrexate
Leflunomide has been compared to methotrexate in several studies. 5 found that leflunomide was as efficacious as methotrexate, with only the reduction of swollen joint count being more marked for methotrexate. 6 also found that leflunomide was effective in treating RA, with similar efficacy to methotrexate but fewer adverse events.
Adverse Events
Leflunomide has been associated with adverse events such as diarrhea, elevated liver enzymes, alopecia, and rash 3, 4. However, 6 found that the incidence of adverse events was lower in the leflunomide group compared to the methotrexate group.
Considerations for Treatment Decision
When deciding between adding leflunomide or Relafen DS, the patient's GI upset intolerance to meloxicam and ibuprofen should be considered. While Relafen DS may be less harsh on the stomach, leflunomide has been shown to be effective in treating rheumatoid arthritis with a relatively acceptable tolerability profile 7. The patient's worsening swelling in her hands and joint pain should also be taken into account, as leflunomide may be more effective in addressing these symptoms.