A NEW APPROACH TO EARLY DETECTION OF ADVERSE EVENTS OF HIGH-RISK MEDICATIONS USING A STRUCTURED, STANDARD, PROTOCOL DRIVEN WEEKLY REMOTE ELECTRONIC MDHAQ 60-SYMPTOM CHECKLIST

Background: A multidimensional health assessment questionnaire (MDHAQ) includes RAPID3, which distinguishes active from control treatments in rheumatoid arthritis clinical trials, and documents change comparably to disease-specific indices in all diseases studied. The MDHAQ also includes a standard, structured 60-symptom checklist, to recognize comorbidities, provide a review of systems, and serve on a fibromyalgia assessment screening tool (FAST3) as a clue to identify patients with fibromyalgia. A new MDHAQ application is to recognize adverse events to high-risk medications on a standard, structured, protocol-driven MDHAQ 60-symptom checklist. A structured list, rather than a “subjective” narrative medical history, is needed as many adverse events are common symptoms, e.g., headache, fatigue; prior negative data facilitates recognition of a new symptom as a possible adverse event. Similar strategies have been reported in oncology, pulmonology and other specialties, but not in rheumatology. Objectives: To use a remote electronic MDHAQ, completed weekly at home, to recognize RAPID3 clinical status changes and adverse events on the 60-symptom checklist, for early detection of medication adverse events. Methods: All patients with all diagnoses complete an MDHAQ at all visits in routine care at one rheumatology site. An electronic flowsheet (Table) is used to monitor 0-30 RAPID3, its components, and report of specific symptoms on the 60-symptom checklist, which appears required to document earlier absence of a common symptom and signal that a common symptom may be an adverse event. Results are depicted for an individual patient with pulmonary fibrosis, seen because of a positive rheumatoid factor. Results: A flowsheet of a pulmonary fibrosis patient over 2018 indicates initial RAPID3 of 14/30 and 10 symptoms at first visit of 19 Jan (Flowsheet). Treatment with low-dose methotrexate (MTX) and prednisone (PRED) led to substantial improvement over 6 months - RAPID3 3.5 and 6 symptoms on 2 Aug. On 15 Aug, MTX and PRED were discontinued by another physician, who prescribed pirfenidone. The patient telephoned on 24 Sep indicating distress. A home-completed remote MDHAQ indicated RAPID3 of 19.5 and 15 symptoms - 7 not reported on 2 Aug were among 16 listed pirfenidone adverse events. Discontinuation of pirfenidone and resumption of PRED and MTX with weekly remote electronic MDHAQ monitoring documented improvement of RAPID3 to 4.2 and 6 symptoms, including resolution of pirfenidone-specific symptoms, on 24 Dec (Flowsheet). Conclusion: Weekly remote electronic MHDAQ monitoring after initiation of a high-risk medication to monitor treatment responses and adverse events may provide a cost-effective approach to reduce morbidity and mortality of adverse events, involving about 10 minutes weekly (2 hours over 12 weeks) of patient time. 78-year-old man monitored over 2018–all data from self-report on MDHAQ – pirfenidone highlighted (many entries deleted for space considerations) Date 19 Jan 2018 25 Jan 2018 2 Aug 2018 15-29 Aug 2018 24 Sep 2018 26 Sep 2018 4 Oct 2018 9 Oct 2018 9 Nov 2018 25 Nov 2018 28 Dec 2018 Site of MDHAQ Clinic Clinic Clinic None Home Home Home Home Home Home Home RAPID3 (0-30)* 14.0 10.2 3.5 ? 19.5 10.2 6.7 6.5 4.8 6.0 4.2 Prednisone mg/day B 40 ↓20 ↓6 D/C 0 R 10 5 5 5 5 5 5 Methotrexate mg/w 20 D/C 0 0 0 0 0 R 10 10 10 pirfenidone B3-9/d 9/d D/C 0 0 3/D D/C 0 #Symptoms (0-60)* 10 5 6 15 15 13 13 6 8 6 Weight loss + + + + + + Feeling sickly + Unusual fatigue + + + + + + + Loss of appetite + + + + + + Stuffy nose + + + + + + + + + Dry mouth + + + + + + + + + Problems with smell/taste + + + + + Cough + + + + + + + + + + Dyspnea + + + + + + + + + + Heartburn/gas + + + + + Joint pain + + + + + Back pain + + Sleep problems + + *Actual total - a few less relevant symptoms deleted for abstract requirements Table 1. RF diagnostic performance in rheumatic diseases Group n Isotype** Cut-off UR/ml Significance AUC (95% CI) Sensitivity % Specificity % Youden Index Sensitivity % Manufacturer cut-off + Specificity % Manufacturer cut-off + RA 22 IgM 135.3 0.06 0.722(0.604 to 0.839) 60% 85.2 0.45 68.2 55.5 Psa 44 IgA 47.2 0.074 0.698(0.553 to 0.842) 54.5 81.8 0.35 54.5 77.3 ASP 44 IgA 39.5 0.080 0.668(0.511 to 0.826) 54.5 88.6 0.43 54.9 79.5 SS 44 IgM 180.6 0.088 0.535(0.088 to 0.708) 54.5 74.4 0.28 68.2 9.3 Healthy 44 IgM 16.3 0.046 0.896(0.806 to 0.986) 77.3 88.9 0.66 68.2 97.8 SLE 41 IgA 42.6 0.073 0.701(0.557 to 0.845) 54.5 85.3 0.39 54.5 73.5 FBM 35 IgM 68.6 0.071 0.752(0.612 to 0.892) 63.6 82.8 0.46 68.2 51.7 OA 38 IgM 48.0 0.053 0.873(0.770 to 0.976) 63.6 96 0.59 68.2 88 PG 20 IgM 117.0 0.076 0.758(0.609 to 0.908) 59.1 89.5 0.49 68.2 63.2 Total 332 ** The isotype with the best AUC for each clinical scenario. + Manufacturer cut-off value: 20UR/ml Disclosure of Interests: Theodore Pincus Shareholder of: Dr. Pincus holds a copyright and trademark on MDHAQ and RAPID3 for which he receives royalties and license fees from profit-making organizations, all of which are used to support further development of quantitative clinical measures for patients and health professionals., Niels Steen Krogh: None declared Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 894Session: Validation of outcome measures and biomarkers (Poster Presentations)