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Comparing Efficacy of Rituximab vs TNF Inhibitors for RA Treatment Post Initial Failure

This case study follows Mrs. JD, a 55-year-old with rheumatoid arthritis (RA) who experienced inadequate response to initial TNF inhibitor therapy after 2.5 years of treatment. Despite good initial responses, disease flaring and poor response to additional DMARDs led to discussions about treatment options. Evidence suggests that switching to Rituximab may offer a more effective alternative compared to cycling between TNF inhibitors, as supported by findings from a UK national cohort study. This case emphasizes the importance of personalized treatment strategies in RA management.

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Comparing Efficacy of Rituximab vs TNF Inhibitors for RA Treatment Post Initial Failure

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  1. House position:Following an inadequate response to a first TNF inhibitor, switching to rituximab is a more effective option than cycling between TNF inhibitors – Con arguments Professor Robert J Moots

  2. Mrs JD • Aged 55 • 3 months history • Exhaustion • Joint pain • Early morning stiffness • On examination • synovitis

  3. Mrs JD: Initial investigations CRP: 68 (<10) mg/dl ESR: 78 (<20) mm/hr Anti-CCP antibody: 60 (<7) u/ml Rheumatoid factor: +ve (titre 1/2560) DAS 28 7.1

  4. Mrs JD: Imaging Erosion

  5. NICE: TNFi in RA • Active disease • DAS 28 > 5.1 • “Adequate” DMARD therapy • Failed 2 DMARDs (incl Mtx) • Treatment > 6/12 • >2/12 at max dose

  6. Mrs JD: Initial Management • Intramuscular methylprednisolone • Combination DMARDs • Methotrexate 15mg once a week • Leflunomide 20mg od • Hydroxychloroquine

  7. Mrs JD: Progress • Good initial response • DAS28 4.5 (steroid) • Still active disease • Mtx increased to 25mg once a week • Depot steroid injections • Still active disease (DAS28 6.1) – off work • Start adalimumab (~6/12 after diagnosis)

  8. Mrs JD: 1st TNFi • Good initial response • DAS28 3.2 • Life back again! • Great 2 years • URTI – stop adalimumab for 2 weeks • Disease flaring – poor response to restart TNFi • DAS 28 6.5

  9. Mrs JD: What to do…? • RA for 2 ½ years • Poor prognosis at presentation • Poor response to DMARDs • Response to adalimumab • Now losing effect… • Swap TNFi? • Rituximab?

  10. Mrs JD: What to do…? Human IgG1 Adalimumab • RA for 2 ½ years • Poor prognosis at presentation • Poor response to DMARDs • Response to adalimumab • Now losing effect… • Swap TNFi? • Rituximab?

  11. Swapping TNFi Can be effective

  12. 1.00 1.00 0.75 0.75 0.50 0.50 0.25 0.25 0.00 0.00 0 0.5 1.0 1.5 2.0 2.5 1.0 1.5 2.0 2.5 0.5 0 First course discontinued due to an adverse event First course of therapy First course discontinued due to inefficacy Outcomes after switching from an initial TNF inhibitor in patients with RA: Results from a large UK national cohort study Drug discontinuation due to inefficacy Drug discontinuation due to adverse events Continuation rate Continuation rate Years Years Hyrich, et al. Arthritis Rheum 2007;56:13–20

  13. Hyrich 2008 **p=0.01 vs stoppers; p=0.03 vs stayers * ** ** Patients from the British Society for Rheumatology Biologics Registry who were nonresponders to initial TNFi and completed 12 months’ follow-up MCID = minimum clinically important difference i.e. those with ≥0.22 unit improvement Hyrich KL et al. Rheumatology 2008;47:1000–5

  14. TNFi: Major Reduction in Bone Progression

  15. TICORA, ASPIRE, PREMIER & TEMPO: Radiographic changes Standard MTX Intensive MTX ADL MTX ADL +MTX I(3mg/kg) +MTX ETN ETN +MTX 12 months 12 months 12 months 18 months MEDIAN

  16. Mrs JD: Progress • Depot steroid im • Swap to etanercept • Good response • DAS 28 2.8 • Response persists (2yrs since swap)

  17. Swap TNFi You know it makes sense – what does Paul Emery know anyway!

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