Comparison of outcomes in antiphospholipid syndrome diagnosed by ISTH versus EULAR criteria

Abstract Introduction Antiphospholipid syndrome (APS) is a hematologic autoimmune condition characterized by the persistent presence of antiphospholipid antibodies along with thrombotic and/or pregnancy morbidity. In addition to thrombosis and pregnancy morbidity, other 'non criteria” manifestations such as thrombocytopenia, nephropathy etc. can occur but were not included in the ISTH Sapporo diagnostic criteria, which require both laboratory and clinical criteria. The recently developed ACR/EULAR classification criteria include several non-criteria manifestations and also further provide weighted points for thrombotic events based on whether thrombosis occurs in presence or absence of other risk factors. The ACE/EULAR criteria also weigh laboratory criteria by the type and titer of antiphospholipid antibodies. Due to such differences between APS diagnostic criteria, we performed a retrospective cohort study to evaluate whether the ACR/EULAR criteria are more likely to identify patients with recurrent thrombotic events and whether patients that meet ACR/EULAR criteria are less likely to “seroconvert” from positive to negative testing over their follow up. Methods We identified all patients who met ISTH criteria for APS diagnosis between 2016 and 2022 at Johns Hopkins Hospital. We then categorized patients as meeting ISTH criteria alone or also meeting ACR/EULAR classification criteria. We then compared the clinical characteristics and outcomes (including recurrent thrombotic events, number of events, and seroconversion from a positive to a negative apL test) between these groups using the Chi squared test and Fischer's exact test for categorical variables and the T test for continuous variables. P <0.05 was considered significant. Results We identified 274 patients who met both clinical and laboratory criteria and were diagnosed with APS by ISTH criteria. Of these, 193 met diagnosis by only the ISTH criteria and 81 also met the ACR/EULAR criteria. Demographic characteristics and prevalence of comorbidities including underlying autoimmune disorders were similar between the groups. The proportion of secondary APS was 70.4% in the ISTH group and 65.4% in the ACR/EULAR group (P>0.05). Thrombotic events occurred in 66.3% in the ISTH group and 97.5% in the ACR/EULAR group (P<0.01). Thrombotic events in the patients who met only ISTH criteria were more likely to be associated with a high risk VTE profile compared to patients meeting ACR/EULAR criteria (5.2% vs 0%, P< 0.01). Thrombotic recurrence (>1 thrombotic event) occurred in 22.8% of patients in the ISTH group and 50.6% in the ACR/EULAR group (P<0.05). The average number of thromboses in the ISTH criteria group was 1.69 compared to 2.14 in the ACR/EULAR group (P<0.01). There was a higher rate of seroconversion in the ACR/EULAR group (38.3%) compared to the ISTH group (7.3%) (p<0.01). When analyzed separately by primary versus secondary APS in the patients meeting ACR/EULAR criteria, seroconversion occurred at a different rate in primary (16.1%) vs secondary (46.4%) APS groups. Returning to a positive test was more common in those with secondary APS (73.1% vs 20.0% of those that seroconverted). Conclusion The ACR/EULAR classification criteria for APS are more likely to identify patients with APS who develop thrombosis in the absence of a high risk VTE profile, along with patients who have recurrent thrombotic events. This suggests that the ACR/EULAR criteria may better reflect APS (versus other risk factors) as the primary driver of thrombotic events. Differences in seroconversion may be due to autoimmunity and/or immunosuppressive therapy, however further analysis is needed to understand the observations between seroconversion among patients in both groups.