A multianalyte assay panel with cell-bound complement activation products demonstrates clinical utility in systemic lupus erythematosus

Abstract

Objective: To evaluate the clinical utility of the multianalyte assay panel (MAP), commercially known as AVISE Lupus test (Exagen Inc.), in patients suspected of SLE.

Methods: A systematic review of medical records of ANA-positive patients with a positive (>0.1) or negative (<-0.1) MAP score was conducted when the MAP was ordered (T0), when the test results were reviewed (T1) and at a later time (T2, ≥8 months after T1). Confidence in the diagnosis of SLE and initiation of hydroxychloroquine (HCQ) were assessed.

Results: A total of 161 patient records from 12 centres were reviewed at T0 and T1. T2 occurred for 90 patients. At T0, low, moderate and high confidence in SLE diagnosis was reported for 58%, 30% and 12% patients, respectively. Confidence in SLE diagnosis increased for the MAP positive, while MAP negative made SLE less likely. Odds of higher confidence in SLE diagnosis increased by 1.74-fold for every unit of increase of the MAP score (p<0.001). Using the MAP-negative/anti-double-stranded DNA-negative patients as reference, the HR of assigning an International Classification of Diseases, Tenth Revision lupus code was 7.02-fold, 11.2-fold and 14.8-fold higher in the low tier-2, high tier-2 and tier-1 positive, respectively (p<0.001). The HR of initiating HCQ therapy after T0 was 2.90-fold, 4.22-fold and 3.98-fold higher, respectively (p<0.001).

Conclusion: The MAP helps increase the confidence in ruling-in and ruling-out SLE in patients suspected of the disease and informs on appropriate treatment decisions.

Keywords: antirheumatic agents; biological products; lupus erythematosus; systemic.

Figure 1

Flow chart of patients included or not in the study. Negative patients had a multianalyte assay panel (MAP) score <−0.1; low tier-2 had a score >0.1 and ≤1; high tier-2 had a score >1; for the tier-1 positives, the score was not calculated as they met the criteria of tier-1 positivity.

Figure 2

Confidence of SLE diagnosis at T1 (panel A) and T2 (panel B) for patients who had a negative, low tier-2, high tier-2 or tier-1 multianalyte assay panel (MAP) score.

Figure 3

Survival analysis (M32). (Panels A and B) Kaplan-Meier time-to-event curves for assignment of the M32 International Classification of Diseases, Tenth Revision (ICD-10) section over time. Curves show the per cent probability of assignment of the M32 section after T0 for the four study groups (tier-1 (multianalyte assay panel (MAP)(Tier1+)), high tier-2 (MAP(High+)), low tier-2 (MAP(Low+)), MAP negative (MAP(−)), together with anti-double-stranded DNA positive (anti-dsDNA(+)) and negative (anti-dsDNA(−)) patients throughout the study. The x-axis reports the number of days since T0. Panels A and B report the same data analysis, with panel B allowing better visualisation of the initial portion of the survival curves. (Panel C) Cox proportional hazard model comparing the MAP score (Neg.: negative; Low: low tier-2; High: high tier-2, Tier 1: tier-1 positive) versus anti-dsDNA antibodies for assignment of the M32 section. In each quadrant, the numerators represent the number of subjects that were assigned an M32 section after T0 (events, n=51 in total) while the denominators represent all subjects in that quadrant. Concordance and p value of the likelihood ratio test are also reported. For data analysis, we used the date of the visit when the M32 section was recorded in the ICD-10 list.

Figure 4

Survival analysis (hydroxychloroquine (HCQ)). (Panel A) Kaplan-Meier time-to-event curves for use of HCQ over time. Curves show the per cent probability of using HCQ after T0 for the four study groups (tier-1 (multianalyte assay panel (MAP)(Tier1+)], high tier-2 (MAP(High+)), low tier-2 (MAP(Low+)), MAP negative (MAP(−)), together with anti-double-stranded DNA positive (anti-dsDNA(+)) and negative (anti-dsDNA(−)) patients throughout the study. TThe x-axis reports the number of days since T0 and is truncated at 56 days to allow better visualisation of the initial portion of the survival curves. (Panel B) Cox proportional hazard model comparing the MAP score (Neg.: negative; Low: low tier-2; High: high tier-2, Tier 1: tier-1 positive) versus anti-dsDNA antibodies for use of HCQ. In each quadrant, the numerators represent the number of subjects on HCQ after T0 (events, n=60 in total) while the denominators represent all subjects in that quadrant. Concordance and p value of the likelihood ratio test are also reported. For data analysis, we used the date of the visit when HCQ use was recorded in the medication list.