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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. Mrs JD. Aged 55 3 months history Exhaustion J oint pain E arly morning stiffness
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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
Mrs JD • Aged 55 • 3 months history • Exhaustion • Joint pain • Early morning stiffness • On examination • synovitis
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
Mrs JD: Imaging Erosion
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
Mrs JD: Initial Management • Intramuscular methylprednisolone • Combination DMARDs • Methotrexate 15mg once a week • Leflunomide 20mg od • Hydroxychloroquine
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)
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
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?
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?
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
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
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
Mrs JD: Progress • Depot steroid im • Swap to etanercept • Good response • DAS 28 2.8 • Response persists (2yrs since swap)
Swap TNFi You know it makes sense – what does Paul Emery know anyway!