Recently, the American College of Rheumatology (ACR) virtually held ACR Convergence 2020, the organization’s annual meeting. At the meeting, researchers shared new insights in the realm of rheumatology; these were centered around treatment, diagnoses, research, and patient care. According to ANCA Vasculitis News, one presentation from Dr. Peter Merkel, MD, discussed how a treatment called avacopan impacted kidney function in patients with ANCA-associated vasculitis (AAV). Learn more in his presentation (Abstract #0432).
Avacopan
Developed by ChemoCentryx, avacopan is an oral, small molecule complement C5a receptor inhibitor. C5a is a pro-inflammatory protein in the complement system. According to the British Society for Immunology, the complement system:
refers to a series of >20 proteins, circulating in the blood and tissue fluids. Most of the proteins are normally inactive, but in response to the recognition of molecular components of microorganisms they become sequentially activated in an enzyme cascade – the activation of one protein enzymatically cleaves and activates the next protein in the cascade.
Basically, the complement system – and C5a – play a role in inflammation and the immune system. Overactivation of the complement system can lead to autoimmune conditions, such as AAV. By inhibiting C5a, avacopan can reduce blood vessel damage and swelling. Currently, avacopan is not approved yet, but it is still under review.
Trial Data
Presented data was sourced from the Phase 3 ADVOCATE clinical trial. During the trial, researchers compared the safety, efficacy, and tolerability of avacopan to prednisone. 330 patients enrolled. They had either granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). During the trial, patients received either 30mg avacopan 2x daily or prednisone. The trial followed patients for a 1-year period. As patients received avacopan and prednisone, they also received standard of care (SC) treatment, which included cyclophosphamide or rituximab in conjunction with azathioprine.
First, researchers determined that avacopan and prednisone were equally effective in allowing patients to experience symptom remission within 6 months. Next, avacopan was also shown to sustain remission over a longer period. However, the therapy was also shown to have benefits for kidney health and function. Avacopan significantly improved kidney health and function compared to prednisone, by increasing glomerular filtration and keeping proteins like albumin in the body. Finally, the therapy slightly improved liver function. Side effects included low white blood cell count and infections. However, the therapy was fairly well-tolerated by trial participants.
Granulomatosis with Polyangiitis (GPA)
An infection or inflammation-causing trigger may cause granulomatosis with polyangiitis (GPA), although doctors are not sure of the exact cause. Once called Wegener’s granulomatosis, GPA is a rare blood vessel disease characterized by blood vessel inflammation throughout the body. Generally, GPA impacts small and medium blood vessels. When these vessels swell, it prevents adequate blood flow and cellular oxygenation. GPA can affect multiple parts of the body. However, it most often impacts the sinuses, lungs, and kidneys. Symptoms include:
- Congestion
- Joint pain
- Fatigue
- Coughing up blood
- Shortness of breath
- Frequent nosebleeds
- Muscle numbness
- Night sweats
- Rashes
- Hearing loss
Microscopic Polyangiitis (MPA)
While the cause of microscopic polyangiitis (MPA) is unknown, many believe it to relate to the immune system. This rare condition is characterized by vasculitis, or blood vessel inflammation. Typically, MPA affects the nervous system, skin, lungs, kidneys, and joints. These systems and organs become damaged as blood vessels narrow and weaken, causing health problems, organ failure, and even blood vessel ruptures. Symptoms vary based on which part of the body is affected. However, potential symptoms include:
- Kidney inflammation and loss of function
- Fatigue
- Shortness of breath or difficulty breathing
- Fever
- Coughing up blood
- Mobility loss
- Muscle and joint pain
- Unintended weight loss
- Appetite loss
- Skin rashes
- Inflammation of the lower extremities
- Bloody urine
