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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

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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


Mrs jd imaging

Mrs JD: Imaging

Erosion


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?


Swapping tnfi can be effective

Swapping TNFi Can be effective


Professor robert j moots

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


Tnfi major reduction in bone progression

TNFi: Major Reduction in Bone Progression


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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