Scientists ID 4 MPA subtypes for better predicting patient outcomes
Each subtype marked by differing characteristics, survival rate: Study
Researchers in Japan have identified four distinct subtypes of microscopic polyangiitis, or MPA — a type of ANCA-associated vasculitis (AAV) — that are associated with different clinical characteristics, which may help in better predicting, and improving, patient outcomes, according to the team.
One subtype was marked mainly by kidney and lung involvement, while another was characterized by elderly onset disease and bodywide inflammation. A third subtype was comprised of younger onset patients with limited organ involvement, and another was characterized mainly by lung involvement without kidney involvement.
With these four subtypes identified, the team then analyzed outcomes after 10 years for each cluster, and found differing survival and relapse rates. According to the team, additional studies may help scientists develop targeted treatment strategies for patients based on these subgroups. That, in turn, could potentially help in lowering mortality, improving patient outcomes, and establishing clinical indicators to aid doctors in prescribing treatment.
“Individualized treatments for each subgroup may be required to improve the prognosis of MPA,” the researchers wrote.
The findings were described in a study titled “Identification of novel clinical subtypes in patients with microscopic polyangiitis using cluster analysis: multicenter REVEAL cohort study” and published in the journal Frontiers in Immunology.
Investigating different clinical characteristics among MPA patients
AAV is a group of autoimmune disorders characterized by inflammation and damage to small blood vessels. MPA is a common type of AAV that involves several organs, such as the kidneys, lungs, and the skin, and is not marked by granulomas, or clumps of inflammatory immune cells, at sites of inflammation.
“MPA is a [variable] disease because its clinical presentation ranges from limited to generalized phenotypes [disease manifestations],” the researchers wrote, adding that “prognosis varies according to organ involvement in MPA.”
Thus, identifying different subgroups of MPA patients with similar clinical characteristics may help in improving outcomes, per the team. Specifically, it could allow clinicians to tailor therapeutic approaches to each patient’s disease manifestations.
To that end, a team led by researchers from the Osaka Medical and Pharmaceutical University retrospectively analyzed data from 189 adults with MPA who were part of a multicenter Japanese observational study called the Registry of Vasculitis Patients to Establish the REAL World Evidence (REVEAL). The patients’ median age was 73 and slightly more than half (54.5%) were women.
The team extracted 11 demographic and clinical variables from the data. These included age at registry entry, blood levels of the inflammatory marker C-reactive protein, or CRP, and of creatinine, a marker of kidney problems. Another variable was the presence of interstitial lung disease, or ILD, a group of diseases marked by lung inflammation and scarring. Seven other organ-involvement items of the Birmingham Vasculitis Activity Score, or BVAS — a standard, validated assessment of AAV severity — also were used.
All data were then input into computer algorithms for cluster, or group, analysis to identify subgroups of MPA patients with shared features.
Data help in predicting outcomes, could be used to personalize treatment
“Four new subgroups with different clinical phenotypes and prognoses were identified” in the analysis, the researchers wrote, noting that each was “unique … with different MPA outcomes.”
Cluster 1, the kidney involvement and diffuse alveolar hemorrhage (DAH)-dominant group, comprised 33 patients. It had the highest rates of kidney involvement (100%) and rapidly progressive glomerulonephritis — a disease affecting the kidney’s filtering units — as seen in 51.5% of patients. The individuals in this group also had the highest levels of creatinine, further indicating more severe kidney disease.
Also, nearly all patients in this subgroup (90.9%) had chest involvement and the highest prevalence of DAH (36.4%), a condition marked by bleeding into the lungs.
A total of 75 patients formed cluster 2, called the elderly onset systemic inflammation group. These patients were the oldest and had the highest CRP levels. This subgroup also had the second highest rates of kidney involvement (88%) and ILD (61.3%), and the second highest creatinine levels. Those in this group also were most frequently affected by symptoms related to the nervous system (65.3%) and those of the ear, nose, and throat (30.7%).
Cluster 3, called the younger-onset limited-organ disease group, involved 45 patients. It was characterized by young age and the highest rates of skin involvement (22.2%) and mucous membranes/eyes involvement (28.9%).
Finally, cluster 4, named the ILD-predominant group without kidney involvement, was composed of 36 patients. They had the highest rate of ILD (88.9%), but no kidney involvement.
Four new subgroups with different clinical phenotypes and prognoses were identified. … [Each was] unique … with different MPA outcomes.
The researchers then compared each cluster based on various outcomes after 10 years. Among the outcomes assessed were overall mortality, respiratory-related mortality, kidney failure-related mortality, and relapse rates. Over a mean follow-up of 4.4 years, 61 patients died, and 32 of these deaths were related to respiratory problems, mainly due to infections.
Patients in cluster 2 had the worst overall and respiratory-related mortality, which was significantly worse than for those in cluster 3. Those in cluster 1 had the worst survival rates without kidney failure and worst relapse rates, which were significantly worse than those in cluster 4.
“This implies a potential need for more aggressive initial treatment therapy in cluster 1 patients with MPA,” the researchers wrote.
The team noted that “cluster 3 had a better prognosis because these patients had fewer cases of severe [kidney] and pulmonary involvement” than those in other clusters.
“The respiratory-related death rate in cluster 4 was the second highest among the four groups; therefore, further studies will be needed to establish clinical indicators for poor prognosis in this ILD-predominant group,” the researchers wrote.
Future studies — particularly ones involving patients of other ethnicities and that follow individuals with MPA over time — are needed to “determine treatment strategies based on these subgroups,” the researchers concluded.
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