Fatigue Persists at High Levels in Some AAV Patients Despite Treatment, Study Shows

People with ANCA-associated vasculitis (AAV) experience much worse fatigue than the general population, and although this eases in many with treatment, a small subgroup can continue to have high fatigue levels, according to a study in 150 newly diagnosed patients who took part in clinical trials.

Those in this subgroup have lower vasculitis activity at diagnosis, but otherwise few identifying markers. They may benefit from interventions that target fatigue-causing factors like pain and social distress, its researchers said.

The study, “The Longitudinal Course of Fatigue in ANCA Associated Vasculitis,” was published in The Journal of Rheumatology.

Outcomes for AAV patients has significantly improved with the introduction of immunosuppressive therapies, but chronic damage and relapses still greatly affect quality of life.

Fatigue, reported by more than 90% of AAV patients, is a symptom that most impacts life quality and daily activities. Previous studies have suggested that poor sleep, pain, and inflammation are all associated with fatigue, and that those with fatigue more likely experience depression, anxiety, and sleep disturbances.

But how fatigue scores change over time in AAV patients is not well-addressed.

To that end, a team of researchers evaluated the levels of fatigue in AAV patients who had participated in two clinical studies, the MYCYC Phase 2/3 trial (NCT00414128) and the RITUXVAS trial (ISRCTN28528813).

In the MYCYC trial, people were randomly assigned to mycophenolate mofetil or pulsed cyclophosphamide to achieve remission, followed by azathioprine as a maintenance therapy. In the RITUXVAS trial, patients received either Rituxan (rituximab) plus two doses of cyclophosphamide or pulsed cyclophosphamide followed by azathioprine.

This study recruited 150 patients — 33 from RITUXVAS and 117 from MYCYC — who had completed the Short Form Health Survey (SF-36) questionnaire, which evaluates self-reported health status and quality of life, including fatigue.

Fatigue assessments were performed every six months for 18 months, and compared to data from 470 healthy people, matched for age and gender, who served as controls.

At diagnosis, AAV patients reported significantly worse levels of fatigue than controls. Fatigue improved in most patients — 105 people or 70% — over the first six months of treatment, and remained stable thereafter.

Despite improvements, fatigue scores of AAV patients post-treatment were higher than healthy controls.

Researchers then analyzed participants according to their fatigue scores and responses to treatment throughout the study: those with low fatigue, moderate-to-high fatigue that improved over time, and those with stable but high fatigue.

Patients with low fatigue (15%) reported fatigue levels comparable to controls, with levels remaining stable throughout the 18 months.

Patients with stable and high fatigue (25%) had consistently worse fatigue scores than all other groups, and their fatigue levels failed to improve with treatment. These patients had lower vasculitis activity scores at diagnosis (measured with the Birmingham Vasculitis Activity Score) compared to those whose fatigue lessened within six months.

Researchers found no factors that could predict which patients would remain with high levels of fatigue, with all groups of patients showing similar levels of kidney function, kidney damage, and inflammation.

Overall, these findings support that several factors may contribute to fatigue in AAV patients, and that disease-associated inflammation plays a small role.

“Fatigue is a symptom that must be targeted in its own right rather than being improved as part of a secondary benefit to existing interventions,” the researchers wrote.

Patients with high and persistence fatigue “may be more likely to benefit from non-pharmaceutical interventions addressing biopsychosocial symptoms such as pain, and social function strategies, which could be commenced at six months when patients are in remission,” they concluded.