Economic Evaluation of Anticyclic Citrullinated Peptide Positivity in Rheumatoid Arthritis.

BACKGROUND: Anticyclic citrullinated peptide (anti-CCP) positivity may be a strong predictor of joint erosion and a potential biomarker for guiding treatment decisions for rheumatoid arthritis (RA). However, limited studies are currently available on the effect of anti-CCP positivity on health care utilization and/or medical costs of RA patients. OBJECTIVE: To investigate short-term and long-term direct health care expenditures associated with anti-CCP positivity in newly diagnosed RA patients. METHODS: A retrospective cohort study was conducted in adult RA patients within a U.S. integrated health care delivery system (January 1, 2007-June 30, 2015). Patients were required to have 2 RA diagnoses and treatment with a conventional or biologic disease-modifying antirheumatic drug (DMARD) within 12 months. The first RA diagnosis date was labeled as the index date, and patients were followed until they left the health plan, died, or reached the end of the study period. Patient demographics, anti-CCP results, comorbid conditions, and health care resource utilization during baseline (12 months before the index date) and follow-up periods were collected. Nationally recognized direct medical costs were assigned to health care utilization to calculate health care costs in 2015 U.S. dollars. The baseline differences between anti-CCP positivity and negativity and differences in censoring during follow-up were addressed using propensity scores. The mean differences in costs were estimated using recycled prediction methods. RESULTS: 2,448 newly diagnosed RA patients were identified and followed for a median of 3.7 years (range = 1-8 years). At baseline, 65.8% of patients were anti-CCP positive. Anti-CCP-positive patients had fewer comorbid conditions at baseline. During the first 12 months of follow-up, median (interquartile range) total health care expenditures for anti-CCP-positive and anti-CCP-negative patients were $6,200 ($3,563-$13,260) and $7,022 ($3,885-$12,995), respectively. After adjusting for baseline differences, total incremental mean cost associated with anti-CCP positivity during the first 12 months was estimated to be $2,163 per patient (P = 0.001). The annual incremental costs in anti-CCP-positive patients became progressively larger over time, from $2,163 during the first year to $5,062 during the fourth year. Anti-CCP positivity was associated with higher prescription, laboratory testing, and rheumatologist utilization. A higher percentage of anti-CCP-positive patients received 1 or more biologic DMARDs (11.6% for anti-CCP-positive vs. 5.7% for anti-CCP negative; P < 0.001) compared with anti-CCP-negative patients during the 12-month follow-up, which resulted in $2,499 in incremental prescription costs (P < 0.001). Total additional burden associated with anti-CCP positivity during the first 4 years was estimated to be $14,089 per patient. CONCLUSIONS: In newly diagnosed RA patients, higher economic burden associated with anti-CCP positivity was mainly driven by prescription costs. DISCLOSURES: This research and manuscript were funded by Bristol-Myers Squibb (BMS). Alemao and Connolly are employees and shareholders of BMS and participated in the design of the study, interpretation of the data, review/revision of the manuscript, and approval of the final version of the manuscript. An and Cheetham received a grant from BMS for this research. At the time of this study, An was employed by Western University of Health Sciences, and Cheetham was employed by Kaiser Permanente Southern California. Bider-Canfield, Kang, and Lin have nothing to disclose. Some study results were presented as a poster at the American College of Rheumatology Annual Meeting; November 5, 2017; San Diego, CA, and at the International Society for Pharmacoeconomics and Outcomes Research Meeting; May 19, 2018; Baltimore, MD.

Rates, factors, reasons, and economic impact associated with switching in rheumatoid arthritis patients newly initiated on biologic disease modifying anti-rheumatic drugs in an integrated healthcare system.

Objectives To identify how many RA patients newly-initiated on bDMARD therapy switch to another bDMARD during the first year of treatment; to evaluate the factors and reasons associated with bDMARD switching; and to compare the RA-related healthcare resource utilization (HCRU) and costs between switchers vs non-switchers during the post-index period. Methods A retrospective cohort study was conducted in RA patients using the Kaiser Permanente Southern California (KPSC) database with the study time period of January 1, 2007 to December 31, 2012. The index date was defined as the date of the first bDMARD prescription. Patients had to have continuous membership eligibility with drug benefit and no prior history of bDMARD during the 24 months prior to the index date. bDMARD switching was defined as a different bDMARD claim during post-index. A multivariable logistic regression model was used to evaluate factors associated with switchers vs non-switchers. Chart notes were reviewed to evaluate reasons for switching from index bDMARD. RA-related HCRU use and costs were evaluated using a generalized linear model (GLM) with gamma distribution and log link function. Results Two hundred and fifty-one patients (12%) switched from their index bDMARD to a different bDMARD during the post-index period. bDMARD switchers were more likely to be female, of Asian/Pacific race, younger than ≤65 years of age, overweight, CCI score ≤2, initiating etanercept or adalimumab, and have a commercial insurance plan compared to non-switchers. Reasons for switching were related mostly to lack or loss of efficacy (∼51%); bDMARD switchers had overall mean adjusted RA related total costs that were 25% higher (p = 0.04) compared to non-switchers. Conclusion It is important for RA patients to receive appropriate therapy and consider bDMARD with different mechanisms of action to decrease subsequent switching, and decrease overall RA related costs as shown in this study.

Update on disease-modifying antirheumatic drugs in the treatment of systemic sclerosis.

Treatment of systemic sclerosis has been somewhat haphazard and treatment has often been "borrowed" from the experience gained from treating other connective tissue diseases. There was a period of time that was focused mainly on organ-specific manifestations of systemic sclerosis and some advance in preventing vital organ damage (such as renal crisis) was achieved. The vast improvement in mortality from the use of ACE inhibitors raises one's hopes for other effective therapeutic interventions. At this juncture, the evidence is strong that the ACE inhibitors that are used in scleroderma renal crisis are disease-modifying, even without proving it by a randomized controlled trial. The evidence is strong that the use of epoprostenol for primary pulmonary hypertension is life-saving; however, whether epoprostenol is life-saving in the pulmonary hypertension in scleroderma remains to be proven. There are suggestions that bosentan (for the pulmonary hypertension of scleroderma), cyclophosphamide (for SSc alveolitis), stem cell transplant, interferon-gamma (for interstitial pulmonary fibrosis), and methotrexate (for the skin thickening of diffuse scleroderma) may improve organ function or functional activities, but whether they are truly disease-modifying remains to be proven. As we increase our understanding of the pathophysiology of systemic sclerosis and we learn how better to design trials for systemic sclerosis, we may be more successful in developing optimal disease-modifying therapy. Although the treatment of systemic sclerosis remains difficult, there are an increasing number of potentially effective regimens that are undergoing clinical investigations. A rational approach to therapy seems possible, based on a hypothesis of the pathogenesis of systemic sclerosis. Thus, there is accumulating evidence that supports the use of prostacyclin derivatives to treat systemic sclerosis, some evidence that antifibrotic regimens may be effective, and moderate evidence that immunosuppression also may be effective in certain stages of this disease.

Using natural language processing and machine learning to identify gout flares from electronic clinical notes.

OBJECTIVE: Gout flares are not well documented by diagnosis codes, making it difficult to conduct accurate database studies. We implemented a computer-based method to automatically identify gout flares using natural language processing (NLP) and machine learning (ML) from electronic clinical notes. METHODS: Of 16,519 patients, 1,264 and 1,192 clinical notes from 2 separate sets of 100 patients were selected as the training and evaluation data sets, respectively, which were reviewed by rheumatologists. We created separate NLP searches to capture different aspects of gout flares. For each note, the NLP search outputs became the ML system inputs, which provided the final classification decisions. The note-level classifications were grouped into patient-level gout flares. Our NLP+ML results were validated using a gold standard data set and compared with the claims-based method used by prior literatures. RESULTS: For 16,519 patients with a diagnosis of gout and a prescription for a urate-lowering therapy, we identified 18,869 clinical notes as gout flare positive (sensitivity 82.1%, specificity 91.5%): 1,402 patients with ≥3 flares (sensitivity 93.5%, specificity 84.6%), 5,954 with 1 or 2 flares, and 9,163 with no flare (sensitivity 98.5%, specificity 96.4%). Our method identified more flare cases (18,869 versus 7,861) and patients with ≥3 flares (1,402 versus 516) when compared to the claims-based method. CONCLUSION: We developed a computer-based method (NLP and ML) to identify gout flares from the clinical notes. Our method was validated as an accurate tool for identifying gout flares with higher sensitivity and specificity compared to previous studies.

New onset systemic lupus erythematosus with pheochromocytoma.

We describe a patient with positive antinuclear and anti-Smith antibodies, proteinuria, and thrombocytopenia suggesting systemic lupus erythematosus (SLE). During hospitalization, the patient developed labile hypertension, tachycardia, and intermittent fever. A computer tomography scan of the abdomen showed an extraadrenal mass, which was confirmed as a pheochromocytoma. After removal of the pheochromocytoma, the patient's symptoms resolved and her serology normalized. Previous case reports describe SLE patients with adrenal pheochromocytomas that presented many years after the diagnosis of lupus. This is a novel case of pheochromocytoma discovered at the onset of SLE, with resolution of SLE manifestations shortly after its removal.