POS1179 POST COVID ARTHRITIS; REACTIVE ARTHRITIS OR RHEUMATIC DISEASE FLARE OR BOTH

Background:Reactive arthritis (ReA) is an emerging arthritis after viral infection especially respiratory and gastrointestinal related viruses. In 2020, SARS-COV2 virus is sweeping worldwide with diverse symptoms and prolonged post-Covid manifestations in which are arthralgia and myalgia are frequently present for days and even months. Interestedly, arthritis in covid era is a part of ReA or a flare of autoimmune disease, it is challenging.(1)Objectives:Our objective was to determine the frequency of musculoskeletal symptoms with SARS-COV2 virus and after recovery as well as its relation to autoimmune diseases flares.Methods:A Prospective study was done on 241 patients who admitted to the Rheumatology clinic from March 2020 to January 2021, complaining from new onset of musculoskeletal symptoms. Detailed history, Examination of systems including Musculoskeletal, laboratory investigation, past history of existing rheumatic disease, and history of infection with covid 19.Results:Among 241 patients with median age 34.4, 36.92% had an existing Rheumatic disease while 63.08% are not. Moreover, 39% of patients had a post history with covid 19 within weeks. The most frequent Musculoskeletal symptoms are myalgia (74.56%), arthralgia (69.36%), and arthritis (10.78%). Furthermore, ReA (Post covid arthritis) accounted (2.07%) especially monoarthritis of Ankle (68.75%) while rheumatic diseases flares (24.48%) as well as new onset rheumatic diseases (39.68%). (p ≤0.001) patients of ReA improved on NSAID and intrarticular injection of glucocorticosteroid.Conclusion:Covid 19 is one of environmental triggers for development of rheumatic disease as well as reactive arthritis post viral infections. ReA is commonly affected the Ankle joint mainly monoarthritis and had improved on oral NSAID and intrarticular injection of Glucocorticosteroid.References:[1]Schett, G., Manger, B., Simon, D. et al. COVID-19 revisiting inflammatory pathways of arthritis. Nat Rev Rheumatol16, 465–470 (2020).Disclosure of Interests:None declared.

POS1088 EFFICACY OF SUBCUTANEOUS TANEZUMAB FOR THE TREATMENT OF OSTEOARTHRITIS OF THE KNEE OR HIP: A POST-HOC SUBGROUP ANALYSIS OF PATIENTS FROM A RANDOMIZED, NSAID-CONTROLLED STUDY WITH A HISTORY OF DEPRESSION, ANXIETY, OR INSOMNIA

Background:Tanezumab is a monoclonal antibody directed against nerve growth factor. It is in development for the treatment of moderate to severe chronic pain associated with osteoarthritis (OA) in adult patients for whom other treatments are ineffective or not appropriate. Phase 3 clinical trials have demonstrated the efficacy of subcutaneous tanezumab versus placebo for pain and function outcomes over various timepoints. Largely similar change from baseline was demonstrated in an oral nonsteroidal anti-inflammatory drug (NSAID)-controlled study.1,2,3,4 The efficacy of some other OA therapies can be dampened in patients with depression, anxiety, or insomnia.5,6,7Objectives:A post-hoc analysis to explore the efficacy of subcutaneous tanezumab after 16 weeks treatment, as compared to oral NSAID, in patients with OA and a history of depression, anxiety, or insomnia at baseline.Methods:Subgroup analysis of data from a randomized, double-blind, double-dummy, active-controlled phase 3 study of subcutaneous tanezumab (2.5 mg or 5 mg every 8 weeks) vs twice daily oral NSAID in patients (≥18 years) with radiographically-confirmed moderate to severe hip or knee OA (Kellgren-Lawrence grade ≥2; NCT02528188).4 Co-primary efficacy endpoints were change from baseline to week 16 in Western Ontario and McMaster Universities OA Index (WOMAC*) Pain and Physical Function subscale scores (both ≥5/10 at randomisation; increasing score indicates increasing pain/disability), and Patient’s Global Assessment of OA (PGA-OA, ≥3/5 at randomisation; increasing score indicates poorer condition). Enrolled patients had a history of inadequate pain relief with acetaminophen; inadequate pain relief with/intolerance to/contraindication to tramadol or opioids; or an unwillingness to take opioids. Patients were on a stable dose of NSAID for ≥30 days before screening. Data are presented as least squares (LS) mean change from baseline to week 16 for the whole population and for subgroups of patients with/without a history of depression, anxiety, or insomnia at baseline. Exploratory statistical analysis was conducted by analysis of covariance. P values were not adjusted for multiplicity. This exploratory post-hoc analysis was not part of the pre-specified hypothesis testing plan or included in any sample size calculations; therefore, comparisons between treatment arms or patient subgroups should be interpreted with caution.Results:Overall, 2996 patients were randomized and received at least one dose of study treatment (subcutaneous tanezumab 2.5 mg: n=1002; subcutaneous tanezumab 5 mg: n=998; oral NSAID: n=996). In this population (comprising patients with or without a history of anxiety, depression or insomnia), all treatments were associated with notable and largely similar magnitude improvements in WOMAC Pain, WOMAC Physical Function, and PGA-OA at week 16 (Figure 1). Across treatment groups, differences in LS mean change from baseline in patients with and without a history of depression, anxiety or insomnia ranged between 0 - 0.34 for WOMAC Pain and Physical Function and 0 - 0.19 for PGA-OA.Conclusion:Patients with a history of depression, anxiety, or insomnia did not appear to experience dampened improvements in pain or function with tanezumab or NSAID, as compared to those without.References:[1]Schnitzer T, et al. JAMA. 2019;322(1):37-48;[2]Berenbaum F, et al. Ann Rheum Dis. 2020;79(6):800-10;[3]Schnitzer T, et al. Semin Arthritis Rheum. 2020;50(3):387-93;[4]Hochberg M, et al. Arthritis Rheumatol. In Press;[5]Sharma A, et al. Open Access Rheumatol. 2016;31(8):103-13;[6]Mallen C, et al. PLoS Med. 2017;14(4):e1002273;[7]Campbell C, et al. Arthritis Care Res. 2015;67(10):1387-96.Acknowledgements:Study sponsored by Pfizer and Eli Lilly and Company. Editorial support was provided by Jennifer Bodkin of Engage Scientific Solutions and funded by Pfizer and Eli Lilly and Company.Disclosure of Interests:Philip J Mease Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sun, UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sun, UCB, Theresa Mallick-Searle Speakers bureau: Allergan, Abbvie, Eli Lilly and Company, Salix, Consultant of: Pfizer, Eli Lilly and Company, Elizabeth Johnston Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Dominique Menuet Employee of: Pfizer, Ruoyong Yang Employee of: Pfizer, Robert J Fountaine Shareholder of: Pfizer, Employee of: Pfizer.

A field trial comparing four oral non-steroidal anti-inflammatory drugs on controlling cautery dehorning pain and stress in calves

The purpose of this study was to compare the analgesic effect of four non-steroidal anti-inflammatory drugs (NSAIDs) administered as a single, standardized, oral dose in dairy calves at the time of cautery dehorning. The NSAIDs investigated have pharmacokinetic properties in cattle that produce persistent plasma concentrations that may provide prolonged analgesia with the added practicality of a simple administration regimen. One hundred and eighty-five Holstein calves aged approximately 50 days old were either sham dehorned (n=31) or cautery dehorned following oral administration of carprofen (n=31), firocoxib (n=31), flunixin meglumine (n=30), meloxicam (n=31) or placebo (n=31) in a randomized, controlled trial. A standard dose of 2.0 mg/kg was administered to all calves receiving an oral NSAID. All calves received local anesthesia prior to actual or sham dehorning. Cortisol concentrations, heart rate, mechanical nociception thresholds, ocular and dehorning area temperatures, and average daily gains were evaluated. A linear mixed effects model with repeated measures was used for statistical analysis. Administration of oral meloxicam, flunixin meglumine, and firocoxib at 2.0 mg/kg resulted in decreased cortisol concentrations compared to placebo treated controls for the first 24 h post-dehorning (AUEC0-24) (P = 0.03). Moreover, firocoxib, flunixin meglumine, and meloxicam attenuated the maximum cortisol concentrations compared to placebo treated calves (P = 0.04, P= 0.02). In calves treated with flunixin meglumine, cortisol concentrations was reduced at 4h (P = 0.04) and 8h (P = 0.02). In addition, analgesic administration was associated with changes in ocular and dehorning area temperature differences (P=0.09). Carprofen and meloxicam reduced heart rates during the entire study period (P = 0.003). Although a treatment effect (P < 0.0001) was observed in the determination of mechanical nociception threshold among all treatment groups, meloxicam expressed marginally significant effects (P = 0.09) among NSAID treated groups dehorned. A single dose of oral meloxicam, flunixin meglumine, or firocoxib administered at 2.0 mg/kg reduced the acute stress response associated with cautery dehorning. However, carprofen administration was associated with increased cortisol concentrations and dehorning area temperatures for the initial 24 h. Given the changes in pain and stress outcome variables assessed in this study, NSAIDs should be administered at the time of dehorning.

Evaluating signals generated in a large-scale sequence symmetry analyses: macrolides and heart failure; and NSAIDs and pneumonia

ObjectiveUsing US claims data and the most up-to-date pharmacoepidemiological study design tools we aimed to investigate two safety signals for (1) macrolides and heart failure; and (2) non-steroidal anti-inflammatory drugs (NSAIDs) and pneumonia generated from a large-scale screening analysis using a self-controlled sequence symmetry design in Danish data.MethodsWe used IBM Marketscan data to conduct two new-user, active-comparator cohort studies. In the macrolides example, the exposure was clarithromycin or azithromycin and the comparator was amoxicillin/clavulanate, in patients with sinusitis. In the NSAIDs example, the exposure was oral NSAIDs and the comparator was topical diclofenac, in patients with osteoarthritis. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) to adjust for approximately 50 investigator-specified confounders in a propensity score (PS) matched analysis. In a secondary analysis, we used high-dimensional PS (hd-PS) to adjust for 200 additional proxy confounders.ResultsWe had 1,012,364 propensity score matched patients exposed to clarithromycin or azithromycin versus amoxicillin/clavulanate. With 162 outcomes among clarithromycin or azithromycin exposed patients and 134 among amoxicillin/clavulanate, the HR for overall heart failure was 1.14 (95% CI 0.90 – 1.43). In the NSAIDs example, we included 94,490 patients after propensity score matching. With 794 pneumonia outcomes among oral NSAID patients and 700 among topical diclofenac, we found HR 0.98 (95% CI 0.89 – 1.09). Some upward bias was suspected as larger HRs were observed in the days immediately following exposure for both the macrolides and NSAIDs examples. We found similar results in the hd-PS matched analyses for both examples.ConclusionOur findings for NSAIDs and pneumonia suggest the original signal may have been due to protopathic or detection bias. Our analyses for macrolides and heart failure with short-term follow-up also suggest bias, although we encourage further research.

Pengaruh Pengetahuan Masyarakat Terhadap Rasionalitas Penggunaan Analgesik Oral Non Steroid Anti-Inflamatory Drug Golongan Non Selective COX-1 dan COX-2 Secara Swamedikasi

ABSTRAKPenelitian ini dilakukan untuk melihat adanya pengaruh tingkat pengetahuan terhadap rasionalitas pasien dalam menggunakan obat oral analgesik NSAID golongan Non Selektif COX-1 & COX-2 pada pengobatanswamedikasi di Apotek Latansa Sidoarjo serta untuk mengetahui adanya pengaruh antara faktor sosiodemografi (usia, jenis kelamin, tingkat pendidikan dan status pekerjaan) terhadap tingkat pengetahuan dan rasionalitas penggunaan obat oral analgesik NSAID Non Selektif COX-1 & COX-2 pada pengobatan swamedikasi di Apotek Latansa Sidoarjo. Penelitian ini merupakan jenis penelitian deskriptif observasional melalui pembagiankuesioner kepada 70 pasien sebagai sampel. Pengumpulan data dilakukan secara prospektif. Hubungan antaravariabel penelitian dianalisis dengan uji statistik Chi Square pada aplikasi statistik SPSS ver 22. Hasil penelitian menunjukkan bahwa responden sebagian besar memiliki pengetahuan yang baik (71,50%) dan swamedikasiyang rasional (75,70%). Tingkat pendidikan menunjukkan adanya pengaruh dengan tingkat pengetahuan (Asymp sig (2-sided) = 0,042 ≤ 0,050) pada tingkat kepercayaan 95%. Dan usia menunjukkan adanya pengaruh dengan rasionalitas penggunaan obat oral analgesik NSAID Non Selektif COX-1 & COX-2 dalam pengobatan swamedikasi (Asymp sig (2-sided) = 0,049 ≤ 0,050) pada tingkat kepercayaan 95%.Hasil analisis dengan uji statistik Chi Square menunjukkan adanya pengaruh antara tingkat pengetahuan pasien terhadap rasionalitas penggunaan obat oral analgesik NSAID Non Selektif COX-1 & COX-2 dalam pengobatan swamedikasi (Asymp sig (2-sided) = 0, 016 ≤ 0,050) pada tingkat kepercayaan 95%.Kata Kunci: swamedikasi, pengetahuan & rasionalitas, analgesik NSAID COX-1 dan COX-2.ABSTRACTThis study was conducted to see the effect of society knowledge on rational use of oral NSAID (Non Selective COX-1 & COX-2) self medication in Latansa Apotek Sidoarjo and to investigate the influence ofsociodemographic factors (age, gender, level education and employment status) on the level of knowledge and rational use of oral NSAID (Non Selective COX-1 & COX-2) self medication in the Latansa Apotek Sidoarjo.This observational study is descriptively through the distribution of questionnaires to 70 patients in the sample. The collection of data carried out prospectively. The relationship between variables was analyzed with statistical test Chi Square on statistical application SPSS ver 22. The level of education showed that have significancy on the level of knowledge (Asymp sig (2-sided) = 0.042 ≤ 0.050) at the 95% confidence level. Ages showed that have significancy on with the rational use oral analgesic NSAIDs Non Selective COX-1 and COX-2 in the treatment swamedikasi (Asymp sig (2-sided) = 0,014 ≤ 0.050) at the 95% confidence level.The result of this study showed that (71,50%) of respondent have good knowledge on NSAID while 75,70% of respondents have appropiate NSAID self-medication behaviors. The statistic analysis showed that knowledge had a significancy on self-medication behavior (Asymp sig (2-sided) = 0, 016 ≤ 0,050) and confidence level 95%.Keywords: Self – medication, Rational use &Knowledge, Analgesic – Non Selective NSAIDS COX-1 And COX-2

Adverse Effects of Topical Nonsteroidal Antiinflammatory Drugs in Older Adults with Osteoarthritis: A Systematic Literature Review

Objective.To systematically review the literature on reported adverse effects (AE) associated with use of topical nonsteroidal antiinflammatory drugs (NSAID) in older adults with osteoarthritis (OA).Methods.A systematic search of Medline (1950 to November 2009), Scopus, Embase, Web of Science, Cochrane databases, Dissertation and American College of Rheumatology meeting abstracts was performed to identify original randomized controlled trials, case reports, observational studies, editorials, or dissertations reporting AE from topical NSAID in older adults with OA. Information was sought on study and participant characteristics, detailed recording of application site, and systemic AE as well as withdrawals due to AE.Results.The initial search yielded 953 articles of which 19 met eligibility criteria. Subjects receiving topical NSAID reported up to 39.3% application site AE, and up to 17.5% systemic AE. Five cases of warfarin potentiation with topical agents were reported, 1 resulting in gastrointestinal bleeding. In formal trials, the withdrawal rate from AE ranged from 0 to 21% in the topical agents, 0 to 25% in the oral NSAID, and 0 to 16% in the placebo group.Conclusion.Although topical NSAID are safer than oral NSAID (fewer severe gastrointestinal AE), a substantial proportion of older adults report systemic AE with topical agents. The withdrawal rate due to AE with topical agents is comparable to that of oral NSAID. Given the safety profile and withdrawal rates described in this study, further data are needed to determine the incremental benefits of topical NSAID compared to other treatment modalities in older adults with OA.