What disease-modifying antirheumatic drugs (DMARDs) can be used in patients with inflammatory arthritis and chronic kidney disease (CKD)?

DMARDs for Inflammatory Arthritis in Patients with CKD

Several DMARDs can be safely used in patients with inflammatory arthritis and chronic kidney disease (CKD), with hydroxychloroquine being the safest option, followed by sulfasalazine, while biological DMARDs such as IL-6 inhibitors show promising efficacy and safety profiles in advanced CKD. 1

Conventional Synthetic DMARDs

First-line Options

• Hydroxychloroquine

  • Considered the safest DMARD in patients with CKD
  • Standard dose: 200-400 mg daily
  • Minimal hepatic metabolism
  • Requires regular ophthalmologic monitoring
  • No dose adjustment needed in CKD 1

• Sulfasalazine

  • Generally safe in stable CKD
  • Starting dose: 500 mg daily with gradual increase to 2-3 g/day
  • Monitor liver function tests every 1-3 months initially 1

DMARDs Requiring Dose Adjustment or Caution

• Methotrexate

  • Use with caution in CKD
  • Primarily excreted by the kidneys (16-30% as unchanged drug)
  • Dose reduction necessary in patients with impaired renal function
  • Contraindicated in severe renal disease 2
  • Consider alternative DMARDs in advanced CKD

• Leflunomide

  • Can be used with caution in mild-moderate CKD
  • Part of recommended DMARD combinations with methotrexate 3
  • Monitor renal function regularly

Biological DMARDs

TNF Inhibitors

• Etanercept

  • May be a safe option in CKD patients, including those on predialysis
  • Better hepatic safety profile compared to other TNF inhibitors
  • Most commonly chosen first-line biologic in CKD patients (34.4%) 4
  • However, drug retention rate may be lower in severe CKD (eGFR <30 mL/min/1.73 m²) 5

• Other TNF inhibitors (adalimumab, certolizumab, infliximab, golimumab)

  • Can be considered in CKD but with careful monitoring
  • Lower retention rates in severe CKD compared to IL-6 inhibitors 5

Non-TNF Biologics

• IL-6 inhibitors (tocilizumab)

  • Demonstrated highest drug retention rate in severe CKD (eGFR <30 mL/min/1.73 m²)
  • Fewer discontinuations due to ineffectiveness in advanced CKD
  • More efficacious as monotherapy compared to other biologics in CKD patients 5
  • Consider as preferred biologic in patients with severe CKD

• T-cell co-stimulation modulators (abatacept)

  • Minimal hepatic metabolism
  • Can be considered in patients with stable CKD 1

• Anti-CD20 monoclonal antibodies (rituximab)

  • Can be considered after inadequate response to other biologics
  • Limited specific data in CKD population

Treatment Algorithm for Inflammatory Arthritis in CKD

1. Mild-Moderate CKD (eGFR >30 mL/min/1.73 m²):

   • First-line: Hydroxychloroquine (200-400 mg daily)
   • Second-line: Add sulfasalazine (up to 2-3 g/day)
   • Third-line: Consider methotrexate with dose adjustment or TNF inhibitors

2. Severe CKD (eGFR <30 mL/min/1.73 m²) or Dialysis:

   • First-line: Hydroxychloroquine
   • Second-line: Consider sulfasalazine with careful monitoring
   • Third-line: IL-6 inhibitors preferred over TNF inhibitors based on higher retention rates and efficacy 5

Monitoring Recommendations

• Regular assessment of renal function (every 1-3 months initially, then every 3-6 months)
• Monitor disease activity using composite measures (DAS28, CDAI, SDAI)
• Target remission or low disease activity within 6 months 1
• Adjust therapy if treatment target not achieved after 3-6 months

Important Considerations

• Avoid NSAIDs when possible in CKD patients due to nephrotoxicity
• Consider comorbidities like hypertension and smoking, which are associated with CKD development in RA patients on biologics 4
• Disease activity control is critical in preventing CKD progression in RA patients
• For patients with amyloidosis and CKD, biologics may help control the underlying inflammatory process

Remember that the choice of DMARD should be based on the severity of both the inflammatory arthritis and the kidney disease, with close collaboration between rheumatologists and nephrologists for optimal management.