Persistence to subcutaneous biological agents in Hungarian patients treated for inflammatory arthritis.

BACKGROUND: The aim of the study was to compare drug survival rate of subcutaneous tumor necrosis factor alpha inhibitors in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis patients in Hungary. METHODS: This was a retrospective analysis using data collected from 5,647 patients over a period of 10 years who were treated with any of the following drugs: adalimumab (ADA), etanercept, certolizumab pegol (CZP), and golimumab (GLM). National Health Insurance Fund's hospital, drug reimbursement, and special reimbursement registry data have been used in this study. Drug survival rate was calculated according to Kaplan-Meier survival analysis. Propensity score matching was used to reduce the potential bias caused by the inhomogeneity resulting from demographic characteristics, patient pathways, or drug administration protocols. Both raw and propensity matched data were subject of pairwise comparison between the four subcutaneous therapies. RESULTS: The overall rate of persistence for the 4 biological therapies was between 53% and 61% after 1 year and between 14% and 19% after 4 years (follow-up time). Pairwise comparisons between therapies showed significant differences with GLM-treated patients showing longer median survival times than patients on other therapies. After propensity matching, these differences remained statistically significant between GLM and ADA or CZP over 4 years. CONCLUSION: Hungarian show longer persistence to GLM compared to ADA and CZP.

Impact of adherence to biological agents on health care resource utilization for patients over the age of 65 years with rheumatoid arthritis.

OBJECTIVE: Poor adherence to therapy increases the patient and societal burden and complexity of chronic diseases such as rheumatoid arthritis (RA). In the past 15 years, biologic disease-modifying anti-rheumatic drugs (DMARDs) have revolutionized the treatment of RA. However, little data are available on the impact of adherence to biologics on health care resources. The objective of the study was to determine the long-term health care resource utilization patterns of RA patients who were adherent to biologic DMARD therapy compared to RA patients who were non-adherent to biologic DMARD therapy in an Ontario population and to determine factors influencing adherence. METHODS: Patients were identified from the Ontario RA Database that contains all RA patients in Ontario, Canada, identified since 1991. The study population included RA patients, aged 65+ years, with a prescription for a biologic DMARD between 2003 and 2013. Exclusion criteria included diagnosis of inflammatory bowel disease, psoriatic arthritis or psoriasis in the 5 years prior to the index date and discontinuation of biologic DMARD, defined as no subsequent prescription during the 12 months after the index date. Adherence was defined as a medication possession ratio of ≥0.8 measured as the proportion of days for which a patient had biologic treatment(s) over a defined follow-up period. Adherent patients were matched to non-adherent patients by propensity score matching. RESULTS: A total of 4,666 RA patients were identified, of whom 2,749 were deemed adherent and 1,917 non-adherent. The age (standard deviation) was 69.9 (5.46) years and 75% were female. Relative rates for resource use (physician visits, emergency visits, hospitalization, home care and rehabilitation) for the matched cohort were significantly lower (P⩽0.0001) in adherent patients. Non-adherent patients' use of oral prednisone (67%) was significantly higher (P⩽0.001) than that of the adherent cohort (56%). CONCLUSION: RA patients adherent to biologic therapy have lower health care resource use and lower steroid use compared to non-adherent patients.

Multiplexed protease assays using element-tagged substrates.

Inductively coupled plasma-mass spectrometry (ICP-MS)-based assays lend themselves to multiplexing due to the high resolution between mass channels, the sensitivity, and the reliability of the technique. Here the potential of ICP-MS-based protease assays is demonstrated with a quadruplex assay of cysteine proteases and metalloproteases. Four orthogonal peptide substrates were synthesized for the proteases calpain-1, caspase-3, matrix metalloprotease-9 (MMP-9), and a disintegrin and metalloprotease-10 (ADAM10). Each substrate carries a biotin tag at the C terminus and a diethylenetriaminepentaacetic acid (DTPA)-based lanthanide complex at the N terminus. The results demonstrate that this is a simple and reproducible analysis technique with excellent correlation between the single and multiplex assay formats.

Development of inductively coupled plasma-mass spectrometry-based protease assays.

Rapid, sensitive, and quantitative assays for proteases are important for drug development and in the diagnosis of disease. Here an assay for protease activity that uses inductively coupled plasma-mass spectrometry (ICP-MS) detection is described. Peptidic alpha-chymotrypsin substrates were synthesized containing a lanthanide ion chelate at the N terminus to provide a distinct elemental tag. A biotin label was appended to the C terminus of the peptide, allowing separation of uncleaved peptide from the enzymatic digestion. The enzyme activity was determined by quantifying the lanthanide ion signal of the peptide cleavage products by ICP-MS. Biotinylated substrates synthesized include Lu-DTPA-Asp-Leu-Leu-Val-Tyr approximately Asp-Lys(biotin) and Lu-DTPA-betaAla-betaAla-betaAla-betaAla-Gly-Ser-Ala-Tyr approximately Gly-Lys-Arg-Lys(biotin)-amide. Parallel assays with a commercially available fluorogenic substrate (Suc-AAPF-AMC) for alpha-chymotrypsin were performed for comparison. Using the ICP-MS assay, enzyme concentrations as low as 2pM could be readily detected, superior to the detection limit of an assay using the alpha-chymotrypsin fluorogenic substrate (Suc-AAPF-AMC). Furthermore, we demonstrated the use of this approach to detect chymotrypsin activity in HeLa cell lysates.