MAINRITSAN • 115 newly diagnosed (92) or relapsing (23) patients with GPA or MPA who achieved remission with CS+CYC • Randomized to: – 500 mg RTX infusion on D1, D15, 5.5 months and every 6 months x 2 (total of 5 infusions over 18 m) – AZA 2 mg/kg x 12m, 1.5 mg/kg x 6 m, 1 mg/kg x 4 m • Primary outcome: rate of major relapse at 28 m Guillevin et al. NEJM 2014;371:1771-80
Results Hazard ratio of major relapse for patients randomized to AZA, was 6.61 (95% CI, 1.56 to 27.96; P=0.002). Hazard ratio of major or minor relapse in patients in the AZA group was 3.53 (95% CI, 1.49 to 8.40; P=0.01). Guillevin L et al. N Engl J Med 2014;371:1771-1780.
Long term follow-up of MAINRITSAN • 60 months • n= (110/115 patients 96%) • Overall survival rate : RIT: 100% AZA: 93 % p=0.045 Terrier et al. A&R 2016 abs 1955
Long term follow-up of MAINRITSAN • Relapse-free survival rates: RIT: 58% AZA: 37% p= 0.012 • Major relapse-free survival rates: RIT: 72% AZA: 49% p= 0.003 • NO difference in survival without SAEs • NO difference in the cumulative GC dose
Long term follow-up of MAINRITSAN • For RIX-treated patients, predictors of major relapse were: – PR3-ANCA positivity – ANCA persistence 12 months after starting maintenance therapy
How long should we keep patients on maintenance therapy?
The REMAIN Trial Randomized Controlled trial of Treatment Withdrawal in the Remission Phase of ANCA Vasculitis Karras et al J AM Soc Nephrol 26:2015 TH-OR025
REMAIN Trial • AAV patients • Remission induction with CYC + prednisone • Maintenance with azathioprine • Randomized at month 18 (1:1) – AZA/PRED until 48 months (C) – Discontinuation of AZA/PRED by 24 months (W) • Primary outcome: rate of relapses during 30- months follow-up
REMAIN Trial 121 patients 22% 66% ESRD in 5 cases in W group versus 0 in C group
Summary • Corticosteroids + Cyclophosphamide remain the medication of choice in life and/or organ- threatening GPA (WG) • Rituximab has the same efficacy as cyclophosphamide in severe disease. It may be superior in relapsing disease. It does not increase the risk of infertility or malignancy
Summary • The role of plasma exchange in organ and/or life threatening manifestations of GPA remains to be determined • Maintenance of remission with rituximab may be the best approach to reduce disease relapse • Withdrawing IS drugs too early after remission is associated with a higher rate of relapses
Case 2 • 25 year old man • Presents with a 2 month history of: – Fatigue – Progessive weight loss of 5 kg (60 kg) • 2 week history of: – Numbness in both feet and right hand
Case 2 • Past history – Asthma confirmed by PFT x 3 years – No hospitalization • Habitus – 5 pack year of smoking – Use of cocaine 1-2/month X 2 years. None x 3 years • Medications: – Advair 250, I puff BID – Montelukast (Singulair) 10 mg OD x 1 year
Physical examination • 37 0 , 120/80, 72/min. 98% O 2 sat on room air • ENT normal • Chest: good A/E. Mild wheezes • Heart, abdomen, MSK: normal • Hypoesthesia right D1-3, weakness thumb abduction, opposition: grip R 120/20, L: 320/20. Hypoesthesia both feet. R ankle dorsiflexion and eversion 3.5/5, inversion 5/5
Laboratory • Hemoglobin: 110 • WBC 7.2 – Neutro 2.0 – Eosinophils: 4.3 • Urine: normal • Creatinine: 78 • CXR normal
What is your diagnosis?
What further investigation(s) would you like in this patient?
ANCA in EGPA • The prevalence of ANCA in patients with eosinophilic granulomatosis with polyangiitis (EGPA) (Churg and Strauss syndrome) is only 40-60% • The sensitivity of a nerve biopsy for the diagnosis of vasculitis is only 50%
What is the role of montelukast in triggering EGPA?
Thorax 2008;63:677-682
• Medication histories in 78 patients with CSS • Case-crossover research design • Exposure to montelukast and other asthma medications during the 3 month “index” period preceding the onset of CSS compared with those of four previous 3-month “control” periods
Montelukast and the risk of CSS Drug OR (95% CI) Montelukast 4.5 (1.5-13.9) Inhaled long-acting beta (2) 3.0 (0.8-10.5) agonists Inhaled corticosteroids 1.7 (0.5-5.4) Oral corticosteroids 4.0 (1.3-12.5) Hauser T et al. Thorax 2008;63:677-82
How would you treat this patient?
What is his Five Factor Score?
What is his five factor score? • Cardiac involvement • GI involvement • CNS involvement • Creatinine > 140 mμol/l • Proteinuria > 1 gm/24 hours Guillevin et al. Medicine 1996;75:17-28
Five Factor Score 0
Arthritis Rheum 2008;58:586-594
Results • 72 patients • 93% achieved remission with CS alone • 35% relapsed • Survival at 1 and 5 years were 100% and 97% respectively
Case 3 • 45 year old man • Bipolar disorder, schizophrenia, asthma • Presents to the ER with a new rash on his lower extremities • Meds: Advair, risperidone, amoxicillin • No fever, chills, sore throat • Some nasal congestion and occasional epistaxis.
Case 3 • Intermittent SOB and chest discomfort x 2 months. • No cough or hemoptysis • No abdominal pain or diarrhea • No numbness or weakness in his extremities • Mild recent joint pain in his knees and ankles
Examination • Rapid Atrial fibrillation 150/min • BP 105/70, SaO2: 97% RA • ENT: no oral or nasal ulcer • Lungs: normal • Heart: normal • Abdomen: soft, no visceromegaly • MSK: no synovitis • Neuro: normal
Skin examination
Investigations in the ER • Hgb: 13.6 • WBC: 3.3 • Plt: 207 • Cr: 85 • INR 0.9 • ALT/AST: N • Urine: normal
Course • Admitted to hospital • IV cardizem. Converts to NSR • Further blood work ordered by rheumatology • Skin biopsy • Started on prednisone 60 mg/day for probable vasculitis
Further investigation • HepBsAg/HepC Ab: negative • Cryoglobulins: negative • ANA: positive 1:320 • Positive IgM ACL • MPO-ANCA: 2.7 • PR3-ANCA: 4.0 • TTE: normal • CXR: normal
What do you think?
Would it be easier if he also had these lesions?
Cocaine/levamisole –induced vasculopathy (CLIV)
Arthritis Care & Research 2011;63:1195-1202
Clinical history • 8 patients seen in one year • Non specific constitutional symptoms 8/8 • Weight loss 3/8 • Overt arthritis 6/8 (ankles, wrists, knees, hands) • Duration of cocaine sue: 2.5-32 years
Physical examination • Extremities and/or • Livedo reticularis 3/8 torso 8/8 • Purpuric lesions 4/8 • Mouth ulcers 5/8 • Ulcers 5/8 • Ear lesions 3/8 • Bullous lesions 5/8 • Face lesions 3/8 • Papular or puslular lesions 4/8 • Skin necrosis 4/8 • Tender erythematous papules on ext fingers 3/8
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