Background:TNFα-inhibitor (TNFi) therapy is effective in controlling several rheumatic diseases and has been shown to reduce pain in patients with arthritis. Opioids are often prescribed for chronic pain, a common issue in inflammatory joint disease.Objectives:To explore the impact of the initiation of TNFi therapy as a first-line biologic disease-modifying anti-rheumatic drug (DMARD) on the prescription rates of opioids in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and undifferentiated arthritis (UA) in Iceland.Methods:All patients receiving biologic DMARD therapy for rheumatic diseases in Iceland are registered in a nationwide database (ICEBIO). The Icelandic Directorate of Health operates a Prescription Medicines Register that includes over 90% of all drug prescriptions in Iceland. The study group included patients with RA, PsA, AS, and UA registered in ICEBIO and for each of them five randomly selected comparators from the general population matched on age, sex, and calendar time. On February 1st2016 we extracted data on all filled opioid analgesic prescriptions two years before and two years after the date of TNFi initiation.Results:Data from 359 RA, 217 AS, 251 PsA and 113 UA patients and 4700 comparators were collected. In total, 75% of patients compared to 43% of comparators received ≥1 opiate prescription during the study period. The proportion of patients using opioids (regardless of dose) two years prior to TNFi initiation was 41%, increasing to 49% the following year. After TNFi initiation the proportion returned to 40% (Figure 1). Despite this, the mean yearly opiate dose used by the patients followed a rising trajectory throughout the study period (Figure 2). In total, patients were prescribed nearly 6 times more opioids than the comparators, corresponding to a bootstrapped mean (95% CI) dose of 818 (601-1073) mg MED per patient and year compared to 139 (111-171) mg for comparators.Figure 1.Percental distributions of opioid analgesic use by dose (according to dispensed prescriptions) among patients with inflammatory arthritis (A) and matched comparators (B). All doses are oral morphine equivalent dose (MED) in milligrams.Figure 2.Bootstrapped mean oral morphine equivalent dose per person per year for patients with inflammatory arthritis (above) and age and sex matched comparators (below). Box edges represent 25-75thpercentiles and whiskers 95% confidence intervals.Conclusion:Three out of four patients with inflammatory arthritis in Iceland use opioid analgesics in the two years prior to and/or after the initiation of TNFi therapy and the mean doses were significantly higher than in matched comparators. The proportion of patients receiving opioids increased before TNFi therapy and then decreased again to the previous level. The initiation of the first-line TNFi did not reduce opioid consumption by dose at the group level. On the contrary, there was a trend towards increasing doses over time in both patients and comparators, possibly reflecting the development of opiate tolerance.Table 1.Baseline demographic data. Mean ± SD unless specified. * defined from diagnosis to baselAll patientsRheumatoid arthritisPsoriatic arthritisAnkylosing spondylitisUndifferentiated arthritisTotal n (%)940 (100)359 (38)251 (27)217 (23)113 (12)Age (years)49 ± 1453 ± 1449 ± 1343 ± 1344 ± 15Disease duration (years)*7.8 ± 8.58.2 ± 8.27.4 ± 7.88.3 ± 10.26.3 ± 6.6Female58%73%59%34%52%Disclosure of Interests:Olafur Palsson: None declared, Thorvardur Love: None declared, Johan K Wallman Consultant of: Consultant for AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma., Meliha C Kapetanovic: None declared, Petur S Gunnarsson: None declared, Björn Gudbjornsson Speakers bureau: Novartis and Amgen
Eco-friendly fluorimetric approaches for the simultaneous estimation of the co-administered ternary mixture: etoposide, moxifloxacin and nalbuphine