What are the treatment options for rheumatoid arthritis (RA) in patients with impaired renal function?

Treatment Options for Rheumatoid Arthritis in Patients with Renal Impairment

For patients with rheumatoid arthritis and impaired renal function, leflunomide is the preferred first-line DMARD as it can be used without dosage modification, while methotrexate should be avoided in patients with eGFR <45 ml/min due to risk of fatal pancytopenia. 1

Assessment of Renal Function

• Evaluate glomerular filtration rate (eGFR) to determine the severity of renal impairment before initiating any DMARD therapy 1
• Monitor renal function regularly during treatment to detect any further deterioration 2
• Consider that renal manifestations in RA patients are now more likely caused by cardiovascular risk factors than by uncontrolled RA disease severity 2

First-Line Treatment Options

Conventional Synthetic DMARDs (csDMARDs)

• Leflunomide: Can be used without dosage modification in renal impairment, making it the preferred first-line agent 1
• Methotrexate: Contraindicated in patients with eGFR <45 ml/min due to unpredictable pharmacokinetics and risk of fatal pancytopenia 1, 2
• Sulfasalazine: Requires dose reduction in moderate to severe renal insufficiency 1
• Hydroxychloroquine: Requires dose reduction in moderate to severe renal impairment 1

Second-Line and Alternative Treatment Options

Biological DMARDs (bDMARDs)

• TNF inhibitors: Etanercept has demonstrated safety and efficacy in RA patients with chronic kidney failure, including those on predialysis 3
• Infliximab: Has been used successfully in RA patients on hemodialysis without observed side effects over extended periods 4
• Most biologics: Can be used without dosage modification in renal impairment due to their high molecular weight (>60 kDa) 1
• Exception: Biologics with molecular weight <60 kDa (e.g., anakinra) require dose reduction in renal impairment 1

Targeted Synthetic DMARDs (tsDMARDs)

• JAK inhibitors: Tofacitinib may need dose adjustment or avoidance in patients with significant renal dysfunction 2

Immunosuppressive Options for Severe Cases

• Cyclophosphamide: Requires dose reduction in moderate and severe renal insufficiency 1
• Azathioprine: Requires dose reduction in moderate and severe renal insufficiency 1
• Mycophenolate mofetil: Requires dose reduction in moderate and severe renal insufficiency 1

Medications to Avoid or Use with Caution

• NSAIDs and COX-2 inhibitors: Limited use due to nephrotoxicity 1, 2
• Gold and cyclosporine: Limited use due to nephrotoxicity 1
• Methotrexate: Avoid in patients with eGFR <45 ml/min 1, 2

Treatment Strategy

1. Initial approach: Start with leflunomide as the anchor DMARD in patients with renal impairment 1
2. If inadequate response: Add or switch to a biologic DMARD, preferably a TNF inhibitor such as etanercept or infliximab 3, 4
3. Treatment target: Aim for remission or low disease activity as in patients without renal impairment 5, 6
4. Monitoring: Assess response within 3 months and adjust therapy if target not reached 5

Special Considerations

• Renal biopsy should be considered in RA patients with abnormal renal function to determine the underlying pathology (amyloidosis, glomerulonephritis, interstitial nephritis) 7
• Patients with RA and renal impairment have a higher risk of infections when treated with immunosuppressive drugs 1
• Consider that some RA patients may have renal involvement directly related to the disease (rheumatoid nephropathy) 7

Treatment Algorithm Based on Renal Function

1. Normal to mildly impaired renal function (eGFR >60 ml/min):

   • Standard RA treatment approach with caution regarding nephrotoxic drugs 1

2. Moderately impaired renal function (eGFR 30-60 ml/min):

   • Leflunomide as first choice 1
   • Reduced doses of sulfasalazine, hydroxychloroquine if used 1
   • Consider biologics if inadequate response 3

3. Severely impaired renal function (eGFR <30 ml/min) or dialysis:

   • Leflunomide or TNF inhibitors (etanercept, infliximab) 1, 3, 4
   • Avoid methotrexate 1
   • Significantly reduce doses of other csDMARDs if used 1