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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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professor robert j moots
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
Mrs JD
  • Aged 55
  • 3 months history
    • Exhaustion
    • Joint pain
    • Early morning stiffness
  • On examination
    • synovitis
mrs jd initial investigations
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

nice tnfi in ra
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
Mrs JD: Initial Management
  • Intramuscular methylprednisolone
  • Combination DMARDs
    • Methotrexate 15mg once a week
    • Leflunomide 20mg od
    • Hydroxychloroquine
mrs jd progress
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 1 st tnfi
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
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 do1
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?
slide12
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
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
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 progress1
Mrs JD: Progress
  • Depot steroid im
  • Swap to etanercept
  • Good response
    • DAS 28 2.8
  • Response persists (2yrs since swap)
swap tnfi
Swap TNFi

You know it makes sense – what does Paul Emery know anyway!

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