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P97 Rituximab treatment for eosinophilic granulomatosis with polyangiitis

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Introduction Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of small vessel vasculitis. Rituximab is a monoclonal antibody directed against CD20 antigen on B cells; randomised clinical trials show… Click to show full abstract

Introduction Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of small vessel vasculitis. Rituximab is a monoclonal antibody directed against CD20 antigen on B cells; randomised clinical trials show it to be effective in vasculitis in ANCA positive patients and those with renal involvement. National Institute for Health and Care Excellence (NICE) guidance allows use of rituximab in some subtypes of small vessel vasculitis: granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) but not EGPA. There is limited evidence for rituximab use for remission induction and maintenance in EGPA; this is off licence and not funded in England and Wales. Mepolizumab, an IL-5 antagonist (IL5A), is NICE-approved for eosinophilic asthma but not EGPA. A trial of mepolizumab in EGPA has shown more weeks of remission and reduced steroid dose.1 In England, IL5A therapy is only available in severe asthma centres with limited access and large catchment areas. By contrast, rituximab is available in any hospital with a rheumatologist or nephrologist to prescribe it. Mepolizumab costs approximately £11000 per patient p.a. Biosimilar rituximab is much cheaper at approximately £1000 a dose: patients receive 1–4 doses a year. Methods We identified all patients with EGPA from clinic records. We cross-referenced the EGPA list with a pharmacy list of all doses of rituximab given to vasculitis patients (either as MabThera or biosimilar Truxima) from 2/4/2008 to 1/6/2019. Results See Table 1 for full results. We found 8 unique EGPA patients, 4 males and 4 females, age range 49–78 years who had received a total 20 doses of rituximab (2–4 doses/patient) over 7 years 2012–2019. No serious adverse effects of rituximab were reported. No patient had had IL5A treatment and none were receiving other biological agents. Previous patient treatments prior to rituximab included steroids, cyclophosphamide, azathioprine and mycophenolate. Conclusions We found rituximab to be safe, for remission induction or maintenance in EGPA. We showed steroid sparing in some patients. Eosinophil reduction was gradual with limited effects on lung function. Rituximab is cost effective, compared with current asthma biologics, and requires further assessment in randomised, comparator, clinical trials. Reference Wechsler ME, et al. NEJM 2017;376(20):1921–32.Abstract P97 Table 1 EGPA Patients Treated with Rituximab Sex Age Sites affected at diagnosis max Eos ANCA maintenance Eos indication for RTX effect of rituximab M 64 rhinitis, nasal polyps, cardiac, rash, arthralgia, neuropathy, peritonitis, renal Bx 5.2 Equivocal 0.3–0.4 Relapsing disease generally better F 62 Dilated cardiomyopathy, eosinophilia, asthma, rhinitis, skin nodules 4.3 Negative 0.0–0.1 Relapsing disease improved asthma, improved FEV1, PEF controlled, eos, decreased, pred reduced 10mg to 5mg F 57 asthma, visual loss, neuropathy (sural nerve biopsy) max sinusitis, rash 5.4 Positive PR3 77 0.4–2.1 Relapsing disease Eos 0.4-1.1 F 49 rhinosinusitis asthma, prev uveitis (recurrent) 2.2 Positive PR3 13 0.1 Steroid sparing minimal, initially worse, pred same 7mg M 78 asthma, pulm eosinophilia, sinus disease, pericardial effusion, weight loss, lethargy 8.8 ANCA 0.1–0.4 Remission induction in remission, pred reduced M 53 eyes, joints, rhinitis, asthma, pulmonary haemorrhage 2.7 Positive PR3 593 0–0.4 2014–15 Relapsing disease on maintenance RTX, Eos remain 0.6-1.0, PR3 99-129 M 52 asthma, rhinosinusitis, pulm eosinophilia, CMR shows eos myocarditis also thrombus 9.0 Negative 0.1–0.3 Remission induction remains in remission F 63 asthma, skin Bx (rash) mononeuritis 9.3 Positive MPO25 0.1–0.4 Remission induction remains in remission Eos=eosinophils, pred=prednisolone, Rx=treatment, RTX=rituximab, PEX=plasma exchange, MP=methylprednisolone, cyclo=cyclophosphamide, CMR=cardiac MRI, Bx=biopsy, SOB=shortness of breath

Keywords: asthma; granulomatosis polyangiitis; rituximab; remission; remission induction

Journal Title: Thorax
Year Published: 2019

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