Session: 331. Thrombotic Microangiopathies/Thrombocytopenias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Bleeding and Clotting, Clinical Research, Health outcomes research, Patient-reported outcomes, Diseases, Thrombotic disorders, Treatment Considerations
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy driven by dysregulation of the complement system leading to predominantly renal dysfunction with high morbidity and mortality. While treatment with terminal complement blockade has improved hematologic and renal outcomes in aHUS, patients continue to experience impaired global health status. Patient experience and symptom burden in the current treatment era have not been characterized.
Methods
We administered Patient-Reported Outcomes Measurement Information System (PROMIS) instruments to patients with aHUS to assess 7 global health domains (PROMIS-29v2.0 including physical function, fatigue, pain, depression, anxiety, participation in social roles, and sleep disturbance), cognitive function (Cognitive Function 8a) and social isolation (Social Isolation 4a). Patient reported outcome (PRO) measures were chosen based on input from clinicians and representatives from the aHUS Alliance, a global patient advocacy group. Numerical variables were reported as median with interquartile range (IQR) or mean ± standard deviation (SD), and categorical variables as counts and percentages. We used the single-sided T test to compare T scores on these instruments with the population norm and the Mann Whitney test to compare groups based on need for dialysis and relapse status. P < 0.05 was considered significant.
Results
Fifty-five individuals (85% female, median (IQR) age 42 (21) years) with aHUS completed the instruments. The median (IQR) time from diagnosis was 50 (72) months. Of respondents, 89% reported confirmatory genetic testing, 87% stated their disease was currently under good control, and 82% were on complement inhibition when surveyed while 15% had discontinued anticomplement therapy; 2 (3.6%) had not been on anticomplement therapy. A majority (69%) required dialysis at some point, 9% remained on dialysis when surveyed, and 24% had undergone a kidney transplant. Regarding disease relapse, 22% had experienced one or more aHUS relapses, 67% never relapsed, and 11% did not know if they had relapsed and were not included in this sub-analysis.
Patients reported the following symptom burden over the preceding 4 weeks: fatigue (80%), headaches (51%), drowsiness (46%), confusion or foggy thinking (44%), difficulty remembering things (44%), nausea (44%), stomach pain (29%), diarrhea (29%), and swelling of the lower extremities (20%). Joint pain, unexplained bruising, and bone pain were also reported (2% each).
Compared to the US population norm (mean ± SD, 50 ± 10), our aHUS cohort had significantly higher scores for anxiety (59.2 ± 9.7, P< 0.001), depression (55.8 ± 9.7, P<0.001), fatigue (59.3 ± 55.8, P< 0.001) and sleep disturbance (53.6 ± 7.5, P < 0.001), and lower scores for physical functioning (44.5 ± 8.9, P<0.001) and cognitive function (41.4 ± 12.0, P<0.011) suggesting overall worse functioning in several domains. Patients who had experienced one or more relapses had lower physical function T scores [39.2 ± 5.4 vs 46.4 ± 8.8, P=0.034] and lower ability to participate in social roles [ 42.7 ± 4.9 vs 49.3 ± 9.3, P=0.048] compared with patients without relapse. T scores on the PRO instruments were not significantly different among patients who received dialysis at any point versus never on dialysis.
Conclusions
In this first study focusing on PROs during long-term follow up of aHUS, patients with aHUS report chronically impaired global health status with reduced physical and cognitive function, and higher levels of fatigue, anxiety, depression, and sleep disturbances compared with the general population. Relapsing aHUS is associated with patient-reported worse physical function and reduced ability to participate in social roles. Our results highlight the need to incorporate PRO assessments in clinical trials of novel agents in aHUS, and for research to evaluate potential factors contributing to poor functional outcomes including ongoing microvascular insults to the central nervous system, treatment-related effects, or another cause.
Disclosures: McCrae: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees; sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Chaturvedi: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alexion, AstraZeneca Rare Disease: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; SOBI: Consultancy, Membership on an entity's Board of Directors or advisory committees.