Creating Clinical Meaning for the Promis Cognitive Function Abilities Instrument: Improving Remission Outcomes for Adults with Thrombotic Thrombocytopenic Purpura

Abstract

Introduction: Patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) describe cognitive concerns years after acute episodes. However, these concerns are not routinely addressed during hematology visits. The Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function abilities survey is an easy to administer, valid, reliable, generic instrument that has not been evaluated in iTTP patients from the United States (US). Therefore, the first aim of this study was to compare PROMIS scores of iTTP patients in remission to the normative US population. Also, research in other disorders reported that a barrier to integrating PROMIS into routine care was physician uncertainty related to interpreting results. PROMIS instruments utilize normative scoring, which lacks clinical meaning. Therefore, creation of clinical severity cut-points (‘mild’, ‘moderate’, 'severe') is critical to facilitate clinical interpretation. The second aim was to create clinical severity thresholds for the PROMIS instrument.Methods: iTTP patients were recruited from 9 US centers (8/2019 to present). Eligibility included: 1) age >18 years, 2) documented ADAMTS13 deficiency (< 10% activity) at diagnosis or during a relapse and 3) > 1-year clinical remission. Following informed consent, patients were administered the PROMIScognitive survey via their preferred mode (online, telephone, or self-administered). The instrument focused on cognitive function over the last 7 days. Responses were a 5-point Likert scale ranging from 'not at all' (indicating poor function) to ‘very much’ (no current problem). Demographics and the PROMIS global health question ('In general, would you say your health is') were also obtained.Descriptive statistics summarized patient scores relative to the US population (mean 50, SD 10) with lower scores indicating worse function. Additionally, we determined the T-score ranges for patients who reported 'not at all/a little bit' on all cognitive items and for those who reported ‘quite a bit/very much’ on all cognitive items. The upper end of the T-score range for patients reporting ‘not at all/a little bit’ determined the threshold for ‘Severe’ impairment and the lower end of the T-score range for those reporting ‘quite a bit/very much’ determined the threshold for ‘No/Mild’ impairment. Scores greater than the threshold for ‘Severe’ but lower than the threshold for ‘No/Mild’ were considered ‘Moderate’ cognitive impairment. Patients were then classified into a severity category based on their T-scores. As a descriptive validity check, we compared the proportion of patients reporting ‘excellent/very good’ on the global health question between the ‘Severe’ and ‘No/Mild’ impairment classifications.Results: To date, 94 patients have completed the study (83% female; 54% White; 34% Black; median age 49 years [range 26-85 years]). Overall the mean cognitive score was 45 (SD 9) compared to the US mean 50 (SD 10). Patients who preferred online administration had a mean score of 47 (SD 9) vs patients who preferred telephone or self-administered (mean score of 43 [SD 9]).T-scores for patients reporting ‘not at all/a little bit’ on all items ranged from 23.4-35.1. Based on T-scores, 14 patients (15%) were then classified as having ‘Severe’ cognitive impairment with T-scores < 35.1 (Figure 1). Only 14% of patients classified as having ‘Severe’ cognitive impairment reported their general health as ‘excellent/very good’. T-scores for patients reporting ‘quite a bit/very much’ on all items ranged from 49.2-68.9. Thirty-one (33%) patients were classified as ‘No/Mild’ impairment with T-scores >49.2 (Figure 1) and 52% of these patients classified their health as ‘excellent/very good’.Conclusion: iTTP patients in remission have descriptively lower cognitive scores versus the US population. Our results are similar to those reported from a cohort of iTTP patients from the United Kingdom (PROMIS cognitive mean 40, SD 8). Further, results showed that patients with cognitive T- scores <35 have severe cognitive impairment vs those with scores >49, who have no/mild cognitive impairment. This is the first study to create clinical severity thresholds for the PROMIS cognitive function abilities instrument. Our data provide clinical meaning for PROMIS which should facilitate clinical use in iTTP by identifying patients with severe impairment who need referral to specialists. [Display omitted] DisclosuresTerrell: Sanofi: Consultancy; Takeda: Consultancy. Journeycake: LFB: Honoraria; HEMA Biologics: Honoraria. Mazepa: Sanofi Aventis: Other; Answering TTP Foundation: Research Funding. Cuker: Novartis: Research Funding; Bayer: Research Funding; Alexion: Research Funding; UpToDate: Patents & Royalties; Synergy: Consultancy; Spark Therapeutics: Research Funding; Pfizer: Research Funding; Novo Nordisk: Research Funding; Sanofi: Research Funding; Takeda: Research Funding. Chaturvedi: Sanofi Genzyme: Other: Advisory board member; Alexion: Other: Advisory board member; Dova: Other: Advisory board member; Argenx: Other: Advisory board member; UCB: Other: Advisory board participation. Lim: Hema Biologics: Honoraria; Dova Pharmaceuticals: Honoraria; Sanofi Genzyme: Honoraria. Gangaraju: Sanofi Genzyme: Consultancy; Alexion: Consultancy. Cataland: Ablynx/Sanofi: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Takeda: Consultancy; Alexion: Consultancy, Research Funding.