ORADE Grant Recipient – Dr. Stephanie Garner

Stephanie Garner was the recipient of a 2017 ORADE Grant . Below is a summary of her learnings:

I would like to thank the ORA for providing me with the opportunity to travel to Tokyo, Japan in March 2017 to attend the 18th International Vasculitis and ANCA Workshop. The theme of the meeting was “Diversity and Integration”. There were over 600 attendees from across the world and a strong Canadian contingent. The meeting had excellent educational content and provided a terrific venue to network.

Here are some of the highlights:

Beware of thrombotic events in ANCA Associated Vasculitis (AAV)

Studies have shown patients with AAV have increased risk of cardiovascular disease and venous thromboembolism due to vascular inflammation and anti-plasminogen activity (Emmi, G 2015). Two groups from Russia and England presented new data on arterial and venous thromboembolic (VTE) events in oral presentations

Makarov et al. (abstract WS8_6) looking at incidence of VTE in AAV presented a cohort of 239 patients (74.6% GPA, 25.4% MPA) with a mean age of 49.6 (range 14-83). The majority of patients had renal (67.9%) and lung (75.6%) involvement. Nephrotic syndrome was present in 8.5% of patients. There were 23 (10.9%) VTE events (including two pulmonary embolisms). The majority (>80%) of patients had evidence of active vasculitis at time of the thrombotic event. Patients with MPA were more likely to clot than patients with GPA (18.9% versus 8.3%, p= 0.04). Specific organ involvement did not appear to predict thrombosis.

Kang et al. (Abstract WS8_7) reviewed venous and arterial thrombosis as well as risk factors for thrombosis using a large retrospective cohort study that included 204 patients with a mean follow-up of five years. They found that the incidence of coronary events (1.65/100 person years), stroke (1.1/100 person years), and VTE (1.47/100 person years) were all much higher than that reported in the general population. Risk factors for thrombosis included age, prior thrombosis, renal involvement, prior ischemic heart disease, MPO positive, low albumin and high CRP.

Perhaps we should be considering antiplatelet agents or anticoagulation in patients with AAV especially in those patients who are MPO positive.

Cost effectiveness of rituximab for maintenance of AAV

The MAINRITSAN-1 trial showed that in their protocol rituximab was superior to azathioprine for maintenance of remission in AAV (Guillevin, L 2014). However, given the cost of rituximab is significantly higher than azathioprine this could hinder uptake of this therapeutic strategy.

Montante et al. (Abstract WS7_3) presented data on an economic evaluation of rituximab versus azathioprine from the MAINRITSAN-1 trial. This trial was a multicenter randomized controlled trial that took place in France between 2008-2012 and included 115 patients. For the economic evaluation they included all hospitalizations, consultations, medications and investigations. Cost data was taken from the French National Health Insurance. They found that the total costs were similar despite the disparity in drug price (rituximab 13,670 euros versus azathioprine 10,046 euros). It was noted that the higher cost of rituximab was partially offset by fewer relapses, side effects and follow-up expenses.

It will be interesting to see how this translates in the Canadian health care system and what the implications are when Rituximab comes off patent.

New therapeutic directions – Tocilizumab in AAV

Interleukin-6 is a multipotent inflammatory cytokine that is involved in the pathogenesis of AAV and it has been suggested Tocilizumab may be efficacious in AAV (Berti, A 2015). During the closing session It was announced that Harigai et al. (Abstract CS_2) will be conducting a 52 week randomized, non-blinded, non-inferiority, parallel group comparison study in Japan of Tocilizumab versus cyclophosphamide in patients with AAV.

Patients will be included if they have ANCA positive active MPA or GPA (BVAS ≥3). Both groups will be initiated on prednisolone 0.8 mg/kg/day with a set tapering schedule. The cyclophosphamide group will receive 3-6 IV infusions and then will be initiated on azathioprine if they achieve remission. The primary endpoints have been defined as the proportion of patients with a BVAS of 0 and ability to taper prednisone to 7.5 mg at week 24.

The potential for having another drug in our armamentarium for this disease is exciting.