Use Of Prescription Nonsteroidal Anti-inflammatory Drugs Research Articles

Frequent use of prescription NSAIDs among people with knee or hip osteoarthritis despite contraindications to or precautions with NSAIDs

ObjectiveTo describe use of Non-steroidal Anti-inflammatory Drugs (NSAID), opioid, and physiotherapy (PT) among persons with newly diagnosed knee or hip osteoarthritis (OA) with and without NSAID contraindications or precautions. DesignWe used population-based register data to identify adults aged ≥35 as of January 1, 2014 residing in Skåne region (Sweden) between 2004-2013, without a previous knee or hip OA diagnosis. Among this cohort, we identified people with incident knee or hip OA diagnosis between 2014-2018, and presence of contraindications to or precautions for oral NSAIDs at the time of OA diagnosis. We estimated the risk of: 1) regular oral NSAID use; 2) regular opioid use; 3) PT during the first year after diagnosis among those with vs. without contraindications or precautions using confounder-adjusted logistic regression with standardization. ResultsWe identified 35,173 persons with newly diagnosed OA, of whom 3,257 and 8,351 had ≥1 contraindication to oral NSAIDs and ≥1 precaution, respectively. Overall, 27% of individuals used oral NSAIDs (with or without opioids or PT), 10% used opioids, and 57% attended PT. Among patients with contraindications, 21% used oral NSAIDs compared to 31% without (absolute adjusted difference -0.06 (95% CIs: -0.08, -0.05)), 53% vs 59% used PT (adjusted difference -0.03 (-0.05, -0.01)), while 14% vs 8% had prescribed dispensed opioids (adjusted difference 0.02 (0.01, 0.03)). Similar results were observed for those with precautions. ConclusionsWe highlight the need for safer treatment options. People with OA and contraindications/precautions to NSAIDs have higher risk of opioid use, slightly lower risk of PT use, and continue to be prescribed NSAIDs. Availability of data and materialsAll the data used in the study are available upon request to the appropriate Swedish National authorities.

Identifying Vulnerabilities to NSAID Adverse Events in the U.S. Population: An Analysis of Preexisting Conditions and Sex.

Purpose: In 2005, the Food and Drug Administration (FDA) issued a decision memorandum regarding nonsteroidal anti-inflammatory drugs (NSAIDs). The memorandum recommended the withdrawal of certain NSAIDs due to potential cardiovascular adverse effects. It highlighted the issue of cardiovascular risk associated with NSAIDs as a class. The NSAID medication guide includes a wide range of adverse drug reactions (ADRs), such as increased blood pressure, liver failure, allergic reactions, heart attack, and intestinal bleeding. Although both sexes have an increased risk of ADRs with NSAID use, females have a greater risk than males due to differences in pharmacodynamics and higher medication concentrations (mg/kg). In particular, females with high blood pressure, coronary heart, kidney, and liver disease are at an additional risk of harm from NSAID ADRs. This study quantifies sex-specific differences and other factors associated with prescription NSAID use. Method: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES), a complex survey conducted by the Centers for Disease Control and Prevention (CDC) in two-year cycles. A survey-weighted logistic regression model was utilized to investigate potential sex differences with prescription NSAIDs in the context of other factors, including kidney disease, hypertension, liver disease, insurance status, coronary heart disease, and age, within the 2011-2018 NHANES survey data. Results: Females reported a slightly higher percentage of high blood pressure and kidney disease than males, while males reported a slightly higher percentage of coronary heart and liver disease than females. Last, the model indicated that females were 58% more likely to have used a prescription NSAID than males. Conclusion: The results confirm that women and people with medical conditions, who would potentially suffer greater harm from NSAID ADRs, are more likely to use a prescription NSAID than individuals without these conditions.

Association of peri-operative prescription of non-steroidal anti-inflammatory drugs with continued prescription of opioids after total knee arthroplasty: a retrospective claims-based cohort study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the mainstays of multimodal pain management. While effective for acute pain control, recent pre-clinical evidence has raised concerns regarding an association between NSAIDs and chronic pain and potential opioid use. Our objective was to explore the association between peri-operative use of prescription NSAIDs and the need for continued opioid prescriptions lasting 90-180 days in previously opioid-naïve patients undergoing total knee arthroplasty. A database of health claims in the USA was used to identify all opioid-naïve adult patients who underwent primary knee arthroplasty between January 2010 and October 2021. We evaluated the magnitude of association between peri-operative prescription NSAID claims and claims for opioids at 90 days postoperatively using multivariable logistic regression models. Secondary outcomes included: the magnitude of association between peri-operative NSAID prescription and claims for opioids at 180 days postoperatively; and identifying other potential factors associated with opioid claims at 90 days postoperatively. After risk adjustment using multivariable logistic regression models in the 789,736-patient cohort, the adjusted odds ratio (95%CI) for a continuous claim of opioids at 90 and 180 days postoperatively among patients with a peri-operative NSAID prescription within 30 days was 1.32 (1.30-1.35), p < 0.001; and 1.12 (1.10-1.15), p < 0.001, respectively. This estimate of effect remained robust at 90 days after accounting for known potential confounders, including pre-existing knee pain and acute postoperative pain severity. Similar analysis of other pain medications (e.g. paracetamol) did not detect such an association. This population-based cohort study suggests that peri-operative prescription NSAID use may be associated with continued opioid prescription claims at 90 and 180 days after knee arthroplasty, even after adjusting for other observed covariates for continuous opioid claims. These novel findings can inform clinical decision-making for post-surgical pain management, risk-benefit discussions with patients and future research.

Trends in Use of Prescription Nonsteroidal Anti-inflammatory Medications Before vs After Implementation of a Florida Law Restricting Opioid Prescribing for Acute Pain

Previous research has shown an immediate reduction in new opioid users and use after implementation of the opioid supply restriction laws. Assessment of the association between opioid restrictions and alternative treatment options, such as nonsteroidal anti-inflammatory drugs (NSAIDs), is needed to evaluate potential unintended consequences for patients requiring analgesia. To evaluate the association between an opioid restriction law in Florida and use of prescription NSAIDs. This quality improvement study used interrupted time series analyses accounting for autocorrelation to estimate immediate and trend changes in the prescribing and use of prescription NSAIDs in Florida before and after implementation of a state law limiting opioid prescriptions to a 3-day supply. Participants were enrollees in a single private health plan of a large university and health system employer in Florida from January 2015 to June 2019. Prescriptions for NSAIDs, ascertained from pharmacy claims data. The following outcomes were calculated monthly per 1000 plan enrollees: (1) number of NSAID users; (2) mean days' supply of NSAIDs per prescription; and (3) mean number of NSAID prescriptions. Individuals were classified as NSAID users if they had at least 1 NSAID prescription in a given month. Analysis was stratified by route of NSAID administration (oral or nonoral). Among 46 783 NSAID users with 79 089 NSAID prescriptions during the study period, the median age was 47 years (interquartile range, 35-57 years). After implementation of the opioid restriction law, the number of NSAID users immediately increased, but the difference was not significant (change, 0.82 per 1000 patients; 95% CI, -0.67 to 2.30 per 1000 patients). No significant change in the days' supply of oral NSAID users occurred (change, 0.21 days per prescription; 95% CI, -1.66 to 2.08 days per prescription). Before implementation of the law, there was a nonsignificant decreasing trend in NSAID prescriptions (rate of change, -0.03 per month per 1000 enrollees; 95% CI, -0.13 to 0.07 per month per 1000 enrollees; after implementation, there was a nonsignificant increase in the number of oral and nonoral NSAID prescriptions (change, 1.49 per 1000 enrollees; 95% CI, -3.38 to 6.37 per 1000 enrollees). In this quality improvement study, prescribing and use of prescription NSAIDs did not increase after implementation of a law restricting opioid analgesic prescriptions in Florida. These findings suggest possible greater use of over-the-counter NSAIDs after implementation of the law, but further research is needed to evaluate changes in the use of nonopioid analgesics and alternative pain therapies.

The Role of Knowledge and Attitudes About Nonsteroidal Anti-inflammatory Drugs in Determining Treatment Use.

ObjectiveThe objective of this study was to evaluate how patient knowledge and beliefs regarding nonsteroidal anti‐inflammatory drugs (NSAIDs) may influence the use of NSAIDs for osteoarthritis (OA).MethodsSurveys of 334 adults with knee and/or hip OA were analyzed in this cross‐sectional study. Familiarity with and perceptions of benefits/risks of NSAID use were measured to assess associations with the use of prescription and nonprescription oral NSAIDs. Multinomial logistic regression models were adjusted for sociodemographic and clinical variables.ResultsIn this sample, 35.9% and 35.6% reported use of oral prescription and nonprescription‐only NSAIDs, respectively. Hispanic participants, compared with non‐Hispanic White participants, had lower perceived benefit (P = 0.005) and risk (P = 0.001) of prescription NSAIDs. The following were associated with prescription NSAID use instead of no NSAID use: having family/friends who used prescription (relative risk ratio [RRR] 3.91; 95% confidence interval [CI] 2.05‐7.47) and over‐the‐counter (OTC) (RRR 3.10; 95% CI 1.65‐5.83) NSAIDs for OA, understanding the consequences of using both prescription (RRR 3.50; 95% CI 1.79‐6.86) and OTC (RRR 2.80; 95% CI 1.39‐5.65) NSAIDs, higher perceived benefit of both prescription (RRR 2.51; 95% CI 1.71‐3.66) and OTC (RRR 1.44; 95% CI 1.01‐2.06) NSAIDs, and lower perceived risk of both types of NSAIDs (prescription: RRR 0.63 [95% CI 0.46‐0.87]; OTC: RRR 0.53 [95% CI 0.37‐0.75]). Similar results were found when we assessed the relationship between these variables and OTC NSAID use versus no oral NSAID use.ConclusionAdults with knee and/or hip OA were more likely to use NSAIDs if they were more familiar with, had an increased perceived benefit of, and had a decreased perceived risk of these drugs. Patients’ perceptions and beliefs about NSAIDs should be evaluated when considering them for treatment.

Assessment of Prescription Analgesic Use in Older Adults With and Without Chronic Kidney Disease and Outcomes

Pain is a common symptom among patients with kidney disease. However, little is known about use of analgesics among patients aged 65 years or older with chronic kidney disease (CKD) who do not receive dialysis treatment. To assess national trends and geographic variations in use of opioids and prescription nonsteroidal anti-inflammatory drugs (NSAIDs) in older adults with and without CKD in the US (2006-2015) and examine associations between use of opioids and patient outcomes. This cohort study used the 5% Medicare claims data (2005-2015) to select 10 retrospective annual cohorts of Medicare Part D beneficiaries aged 65 years and older from 2006 to 2015 and a retrospective longitudinal cohort. Data were analyzed in August 2019. CKD status and other comorbidities identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Analgesic use was measured by overall use (proportion of ever used opioids/NSAIDs), long-term use (prescribed >90 days), and cumulative use (total annual days' supply). Patient outcomes included progression to end-stage kidney disease (ESKD) and all-cause mortality. A total of 6 260 454 beneficiaries (9.6% identified with CKD by claims) were selected in the annual cohorts and 649 339 beneficiaries (8.3% identified with CKD) were selected in the longitudinal cohort. There was significant growth in opioid use (31.2%-42.4%) and NSAID use (10.7%-16.6%) among patients aged 65 years and older with CKD from 2006 to 2015. Long-term use of opioids increased during 2006 to 2014 (25.8%-36.7%) but decreased through 2015 at 35.6%, while long-term use of NSAIDs remained stable. Opioid use was higher in patients with CKD, particularly CKD stages 4 to 5 (odds ratio [OR], 1.35; 95% CI, 1.33-1.37; P < .001) compared with non-CKD. NSAID use was lower in patients with CKD stages 4 to 5 (OR, 0.55; 95% CI, 0.54-0.56; P < .001). Substantial geographic variations in analgesic use were observed across states (opioid use in CKD: 24.7%-54.3%; NSAID use in CKD: 11.2%-20.8%, 2012-2015). Opioid use was associated with progression to ESKD (hazard ratio [HR], 1.10; 95% CI, 1.04-1.16; P = .001) and death (HR, 1.19; 95% CI, 1.18-1.20; P < .001) independent of CKD status and other covariates. There was an inverse association between NSAID use and death (HR, 0.84; 95% CI, 0.83-0.85; P < .001). Among Medicare patients with CKD, use of prescription analgesics, both opioid and NSAID, increased from 2006 to 2015. Optimizing pain management in a complex condition such as kidney disease should remain a priority for clinicians and researchers alike.

Pharmacological Management of Osteoarthritis With a Focus on Symptomatic Slow-Acting Drugs: Recommendations From Leading Russian Experts.

This article describes an updated stepwise algorithm for the pharmacological management of osteoarthritis (OA) to establish a treatment method for patients with OA. In step 1, background maintenance therapy includes symptomatic slow-acting drugs for OA, especially prescription crystalline glucosamine sulfate product, for which the high-quality evidence base of efficacy is unequivocal, or prescription chondroitin sulfate. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol only as rescue analgesia is given on top of the background therapy. Step 2: For patients with persistent OA symptoms, the use of oral NSAIDs is mandatory for maintaining supportive therapy with symptomatic slow-acting drugs for OA. It is recommended to properly stratify patients and carefully select oral NSAID therapy to maximize the benefit-to-risk ratio. Intra-articular hyaluronic acid and intra-articular corticosteroids are recommended as well in step 2 of the algorithm, especially for patients who do not respond to the previous therapies. Step 3: Duloxetine is considered along with the previous procedures, especially in patients with pain from central sensitization. Step 4: Total joint replacement is recommended for patients with severe symptoms and poor quality of life. The current guidelines and literature review provide evidence-based recommendations supported by clinical experience on how to organize the treatment process in patients with knee OA applicable in the Russian clinical practice. International evidence-based guidelines lack consensus on different treatments, including the use of prescription crystalline glucosamine sulfate, NSAIDs, and intra-articular hyaluronic acid. The content of this article needs a further discussion about the clinical evidence and harmonization of recommendations for knee OA management.

Association between NSAID Exposure and Kidney Function Decline in Primary Care Patients

There are limited data evaluating chronic nonsteroidal anti-inflammatory drug (NSAID) exposure and decline in kidney function in primary care practice where rates of NSAID prescribing are high (1,2). The majority of published observational studies have evaluated the association of prescription NSAID use with AKI using claims data in focused geographic areas outside of the United States (1). It is estimated that >36 million Americans use over-the-counter (OTC) NSAIDs and data suggest that many users, regardless of age, exceed the recommended dose (1,3,4). Education materials for prescription ( e.g ., Food and Drug Administration Medication Guide) and OTC (label) NSAIDs have also been noted to have content that is not aligned with the universal precautions for health literacy. Poor literacy around NSAID education materials has been documented among primary care patients with CKD (5). This study sought to evaluate eGFR changes associated with chronic NSAID exposure in a large, geographically vast, primary care cohort using data from the DARTNet Practice Performance Registry receiving prescription and OTC NSAIDs (6). This project was determined to not require oversight by the University of Michigan Institutional Review Board. This determination was based on the fact that the data set analyzed had no protected health information. Eligible patients were ≥18 years old and had at least two eGFR measurements (between 29 ml/min per 1.73 m2) at least 3 months apart. Baseline was defined as the first qualifying eGFR during the study period of January 1, …

Abstract P372: U.S. National Estimates of Prescription Nonsteroidal Anti-inflammatory Drugs Among Patients With Cardiovascular Disease

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, fever, and inflammation, but their ubiquitous use has led to concerns over increased risk of adverse cardiovascular (CV) events, particularly in patients with established CV disease (CVD). In 2005, the FDA revised labels for all NSAIDs to include a boxed warning highlighting the potential for increased CV risk. However, little is known regarding real-world prescribing of NSAIDs among patients with CVD. Our objective was to characterize the use of prescription NSAIDs among patients with CVD from 1988-2016 in the U.S. Methods: Using cross-sectional National Health and Nutrition Examination Survey (NHANES) data from 1988-1994 and 1999-2016, we included participants aged ≥18 years with hypertension (defined by self-report, mean blood pressure ≥140/90, or use of an antihypertensive medication), or aged ≥20 years with ≥1 of the following self-reported heart disease conditions: congestive heart failure (CHF), coronary heart disease (CHD), angina, myocardial infarction (MI), or stroke. Survey-weighted data were analyzed to assess prevalence and trends of prescription NSAID use within each CVD population in 6-year examination periods. Results: Overall, prescription NSAID use declined among all U.S. CVD populations over the study period. Prevalence of prescription NSAID use was highest during the 1999-2004 examination years, but thereafter, declined during the 2005-2010 examination years for those with hypertension (13.9% to 8.8%), CHF (14.6% to 8.5%), CHD (16.3% to 7.0%), angina (17.6% to 9.73%), MI (16.1% to 8.2%), and stroke (15.7% to 8.8%). Use of prescription NSAIDs since the 2005-2010 examination years has remained consistent in all CVD populations. These decreases were driven in part by reduced use of COX-2-selective NSAIDs, whereas non-selective NSAID use among all CVD populations was relatively steady from 1999 to 2016. Conclusions: Prescription NSAID use among patients with CVD appears to have declined from 1988 to 2016, primarily because of less COX-2 NSAID use following removal of 2 approved agents. Otherwise, the prevalence of prescription NSAIDs has remained somewhat stable and relatively high among these high-risk CV populations. Our results suggest additional efforts may be needed to limit the use of NSAIDs among patients with CVD, given that these agents are known to be associated with adverse CVD outcomes.

Prescription Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Depression among Adults with Inflammatory Chronic Conditions in the United States.

The association of prescription NSAIDs to presence of depression among adults with inflammatory chronic conditions in adults with and without depression and seeking care in routine clinical practice remains unknown. We examined the association of prescription NSAIDs to depression among adults with inflammatory chronic conditions in a nationally representative sample of the US non-institutionalized civilian population. We used a retrospective cross-sectional design. Data on 10,713 adults with inflammatory chronic conditions were derived from 2015 Medical Expenditure Panel Survey (MEPS). The dependent variable was the presence or absence of depression and the key independent variable was prescription NSAIDs use. Logistic regression models were used to examine the adjusted associations of prescription NSAIDs to depression. In these regressions, other independent variables (biological, sociocultural, socio-economic, access to healthcare services, medical conditions and treatment factors, behavioural, and environmental factors) that may affect the relationship of prescription NSAIDs to depression were also included. All analyses accounted for the complex survey design of MEPS. Overall, 18.2% reported depression. Almost 21% used prescription NSAIDs. In the unadjusted model, prescription NSAIDs use had higher odds of depression (OR = 1.59;95%CI = [1.40, 1.82]) as compared to those without NSAIDs. In the fully-adjusted logistic regression model, with controls for other independent variables, adults using prescription NSAIDs had no significant association with depression (AOR = 0.97;95%CI = [0.84, 1.13]) compared to those without NSAIDs. In this first real-world study of all adults (with and without depression) in the US, we did not observe a statistically significant association of prescription NSAIDs to the presence of depression.

PMU38 ASSOCIATION OF PRESCRIPTION NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) WITH DEPRESSION AMONG ADULTS WITH INFLAMMATORY CHRONIC CONDITIONS IN THE UNITED STATES

The study objective was to assess the association between prescription NSAIDs and depression among adults with inflammatory chronic conditions. Some randomized clinical trials have demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) can be beneficial in reducing depressive symptoms among adults with depression. As depression is often considered as an inflammatory disease, NSAIDs may also reduce the risk of depression by reducing inflammation. We used a retrospective cross-sectional design. Data were derived from 2015 Medical Expenditure Panel Survey (MEPS), a nationally representative sample of the US non-institutionalized civilian population. Inflammatory conditions included arthritis, asthma, cancer, cardiovascular disease, chronic obstructive pulmonary disease (COPD), and diabetes. The dependent variable was the presence or absence of depression and the key independent variable was prescription NSAIDs use. Logistic regression models were used to examine the adjusted associations between NSAIDs and depression. In these regressions, other independent variables (biological, sociocultural, socio-economic, access to healthcare services, medical conditions, behavioral and environmental factors) that may affect the relationship between NSAIDs and depression were also included. All analyses accounted for the complex survey design of MEPS. The study sample consisted of 11,714 adults, representing approximately 124.5 million adults with inflammatory conditions. Overall, 18.2% reported depression and 21% used prescription NSAIDs. A higher percentage of adults using NSAIDs reported depression compared to those without NSAIDS use (23.5% vs 16%;OR=1.59;95%CI=1.40,1.82). In the fully-adjusted logistic regression model, with controls for biological (sex, age, race/ethnicity), sociocultural, socio-economic, access to healthcare services, medical conditions including pain, behavioral and environmental factors, adults using prescription NSAIDs had higher odds of depression (AOR=1.24;95%CI=[1.07,1.43]) compared to those without NSAIDs. In this first real-world study of all adults (with and without depression) in the US, we observed a positive association between prescription NSAIDs and the presence of depression.

Nonsteroidal anti-inflammatory drug use and risk of acute kidney injury and hyperkalemia in older adults: a population-based study.

Clinical guidelines caution against nonsteroidal anti-inflammatory drug (NSAID) use in older adults. The study objective was to quantify the 30-day risk of acute kidney injury (AKI) and hyperkalemia in older adults after NSAID initiation and to develop a model to predict these outcomes. We conducted a population-based retrospective cohort study in Ontario, Canada from 2007 to 2015 of patients ≥66 years. We matched 46107 new NSAID users with 46107 nonusers with similar baseline health. The primary outcome was 30-day risk of AKI and secondary outcomes were hyperkalemia and all-cause mortality. NSAID use versus nonuse was associated with a higher 30-day risk of AKI {380 [0.82%] versus 272 [0.59%]; odds ratio (OR) 1.41 [95% confidence interval (CI) 1.20-1.65]} and hyperkalemia [184 (0.40%) versus 123 (0.27%); OR 1.50 (95% CI 1.20-1.89); risk difference 0.23% (95% CI 0.13-0.34)]. There was no association between NSAID use and all-cause mortality. A prediction model incorporated six predictors of AKI or hyperkalemia: older age, male gender, lower baseline estimated glomerular filtration rate, higher baseline serum potassium, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use or diuretic use. This model had moderate discrimination [C-statistic 0.72 (95% CI 0.70-0.74)] and good calibration. In older adults, new NSAID use compared with nonuse was associated with a higher 30-day risk of AKI and hyperkalemia but not all-cause mortality. Prescription NSAID use among many older adults may be safe, but providers should use caution and assess individual risk.

Biologic Disease-Modifying Antirheumatic Drugs and Risk of Multiple Myeloma

INTRODUCTIONBiologic disease-modifying antirheumatic drugs (DMARDs) are used more frequently and earlier in the course of rheumatologic conditions in a treat-to-target approach. These medications act on proteins and cytokines with potential pro- and anti-malignancy roles, including tumor necrosis factor-alpha (TNF), human interleukin (IL) receptors and B- and T-cell functions. There is concern for hematologic malignancy with some but not all biologic DMARDs. Little is known about possible associations between these medications and development of multiple myeloma (MM). Our purpose was to determine risk of MM in relation to biologic DMARD treatment, duration of use and by biologic target in a large cohort of patients with rheumatologic conditions. METHODSWe conducted a nested case-control study within a cohort of adults undergoing active treatment for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Patients were sampled from a population of commercially-insured U.S. health plan enrollees in the Truven Health MarketScan Research Database between 2009 and 2015. MM cases were ascertained using validated algorithms for administrative data. Up to ten controls from the overall cohort were matched to each MM case on age, sex and rheumatologic indication using incidence density sampling with replacement. Index date was defined as the date of MM diagnosis for a case and corresponding time at-risk for matched controls. Exposure was defined as both treatment and duration of biologic DMARD use including TNF inhibitor (etanercept, infliximab, adalimumab, golimumab, certolizumab pegol), IL-6 receptor antagonist (tocilizumab), T-cell targeted (abatacept) and B-cell depleting (rituximab) agents and were determined from health claims and pharmacy dispensing data. Data on rheumatologic indication, comorbid conditions and treatment with prescription nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and conventional synthetic DMARDs (hydroxychloroquine, sulfasalazine, methotrexate, leflunomide) were documented in the 12 month baseline period and during follow up as potential confounders. An exposure lag time of 365 days was used to minimize protopathic bias. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for risk of MM associated with biologic DMARDs. RESULTSFrom a retrospective cohort of 56866 adult patients with rheumatologic conditions, 287 MM cases and 2760 matched controls were identified. Compared to controls, a higher proportion of cases had Charlson comorbidity scores of 2 or greater (24% vs 18%) and used oral corticosteroids during follow up (67% vs 61%). Cases and controls were similar with respect to use of prescription NSAIDs (56% vs 59%) and use of conventional DMARDs (63% vs 67%). Use of biologic DMARDs overall was similar between cases and controls (14% vs 15%), although cases had a slightly lower proportion of etanercept users (5% vs 7%) and a slightly higher proportion of tocilizumab users (1.4% vs 0.4%). Biologic DMARD users were younger, more likely to have psoriatic arthritis or ankylosing spondylitis, lower comorbidity and greater use of concomitant NSAIDs and oral corticosteroids.Risk of MM was neither associated with biologic DMARD use overall (OR 0.84; 95% CI 0.57, 1.26; P=0.40) nor with longer duration of biologic DMARD use (>2.5 years: OR 0.72; 95% CI 0.34, 1.52; P=0.39). However, compared to patients treated with only conventional DMARDs, those receiving concomitant conventional plus biologic DMARDs had a 48% lower risk of developing MM (OR 0.52; 95% CI 0.30, 0.88; P=0.02). Associations with MM appeared to differ by specific biologic DMARD agent with estimates suggesting a lowered risk of MM with use of etanercept (OR 0.55; 95% CI 0.30, 1.02; P=0.06) and greater risk with use of tocilizumab (OR 4.33; 95% CI 1.33, 14.19; P=0.02) that was statistically significant, although confidence intervals were wide. CONCLUSIONSThe potential influence of biologic DMARDs on multiple myeloma is complex. We found that immune suppression with conventional plus biologic DMARDs is inversely associated with MM risk in patients with rheumatologic conditions, but this association differed by biologic drug target. Further research is needed to understand the roles of DMARDs targeting TNF and IL-6 in relation to subsequent myeloma pathogenesis. DisclosuresPatel:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Honoraria.

Frequency and Associations of Prescription Nonsteroidal Anti-inflammatory Drug Use Among Patients With a Musculoskeletal Disorder and Hypertension, Heart Failure, or Chronic Kidney Disease

International nephrology societies advise against nonsteroidal anti-inflammatory drug (NSAID) use in patients with hypertension, heart failure, or chronic kidney disease (CKD); however, recent studies have not investigated the frequency or associations of use in these patients. To estimate the frequency of and variation in prescription NSAID use among high-risk patients, to identify characteristics associated with prescription NSAID use, and to investigate whether use is associated with short-term, safety-related outcomes. In this retrospective cohort study, administrative claims databases were linked to create a cohort of primary care visits for a musculoskeletal disorder involving patients 65 years and older with a history of hypertension, heart failure, or CKD between April 1, 2012, and March 31, 2016, in Ontario, Canada. Prescription NSAID use was defined as at least 1 patient-level Ontario Drug Benefit claim for a prescription NSAID dispensing within 7 days after a visit. Multiple cardiovascular and renal safety-related outcomes were observed between 8 and 37 days after each visit, including cardiac complications (any emergency department visit or hospitalization for cardiovascular disease), renal complications (any hospitalization for hyperkalemia, acute kidney injury, or dialysis), and death. The study identified 2 415 291 musculoskeletal-related primary care visits by 814 049 older adults (mean [SD] age, 75.3 [4.0] years; 61.1% female) with hypertension, heart failure, or CKD, of which 224 825 (9.3%) were followed by prescription NSAID use. The median physician-level prescribing rate was 11.0% (interquartile range, 6.7%-16.7%) among 7365 primary care physicians. Within a sample of 35 552 matched patient pairs, each consisting of an exposed and nonexposed patient matched on the logit of their propensity score for prescription NSAID use (exposure), the study found similar rates of cardiac complications (288 [0.8%] vs 279 [0.8%]), renal complications (34 [0.1%] vs 33 [0.1%]), and death (27 [0.1%] vs 30 [0.1%]). For cardiovascular and renal-safety related outcomes, there was no difference between exposed patients (308 [0.9%]) and nonexposed patients (300 [0.8%]) (absolute risk reduction, 0.0003; 95% CI, -0.001 to 0.002; P = .74). While prescription NSAID use in primary care was frequent among high-risk patients, with widespread physician-level variation, use was not associated with increased risk of short-term, safety-related outcomes.

Association of Household Opioid Availability and Prescription Opioid Initiation Among Household Members

Increases in prescription opioid use in the United States have been attributed to changing prescribing guidelines and attitudes toward pain relief; however, the spread of opioid use within households through drug diversion may also be a contributing factor. To investigate whether individuals living in a household with a prescription opioid user are more likely to initiate prescription opioids themselves, compared with individuals in households with a prescription nonsteroidal anti-inflammatory drug (NSAID) user. This was a retrospective cohort study using administrative health care claims data from 2000 to 2014 of commercial insurance beneficiaries sharing a health plan with continuous prescription drug coverage, without opioid or NSAID use in the prior year. Enrollees were followed from the date of the first prescription filled by a household member for an eligible opioid or NSAID until initiation of prescription opioids, disenrollment, or administrative censoring after 1 year or the end of follow-up on December 31, 2014. Risk of opioid initiation was derived from inverse probability-weighted (IPW) Kaplan-Meier estimators that adjusted for potential confounders, prognostic factors, and predictors of censoring. Outpatient pharmacy dispensing of a prescription opioid or prescription NSAID. Incident outpatient pharmacy fill for a prescription opioid by a household member. From 2000 to 2014, 12 695 280 individuals were exposed to prescription opioids and 6 359 639 to prescription NSAIDS through an index prescription to a household member. The IPW estimated risk of opioid initiation in the subsequent year was 11.83% (95% CI, 11.81%-11.85%) among individuals exposed to prescription opioids in the household, compared with 11.11% (95% CI, 11.09%-11.14%) among individuals exposed to prescription NSAIDs, resulting in a risk difference of 0.71% (95% CI, 0.68%-0.74%). An unmeasured confounder that is modestly associated with the exposure (eg, prevalence difference = 0.9%) and the outcome (eg, risk difference = 0.9) after adjustment for all measured variables could explain our observed estimate of the overall risk difference (0.71%). Living in a household with a prescription opioid user may increase risk of prescription opioid use, which may reflect both increased access to these products as well as shared risk factors, such as prescriber preference and prescription drug monitoring.

Use of Analgesics (Opioids and Nonsteroidal Anti-Inflammatory Drugs) and Dementia-Related Neuropathology in a Community-Based Autopsy Cohort.

Opioids may influence the development of Alzheimer's disease (AD). Some studies have observed AD pathology in the brains of opioid abusers. No study has examined the association between prescription opioid use and dementia-related neuropathologic changes. To examine the relationship between prescription opioid or NSAID use and dementia-related neuropathologic changes. Within a community-based autopsy cohort (N = 420), we ascertained opioid and nonsteroidal anti-inflammatory drug (NSAID) use over a 10-year period from automated pharmacy data and calculated total standardized daily doses (TSDDs). A neuropathologist assessed outcomes including neuritic plaques, neurofibrillary tangles, and macroscopic infarcts. Outcome measures were dichotomized using established cutpoints. We used modified Poisson regression to calculate adjusted relative risks (RR) and 95% confidence intervals (CI), accounting for participant characteristics and using weighting to account for possible selection bias related to selection into the autopsy sample. Heavier opioid exposure was not associated with greater neuropathologic changes. For neuritic plaques, the adjusted RR [95% CI] was 0.99 [0.64-1.47] for 91+ TSDDs of opioids versus little to no use, and for neurofibrillary tangles, 0.97 [0.49-1.78]. People with heavy NSAID use had higher risk of neuritic plaques (RR 1.39 [1.01-1.89]) than those with little to no use, as we have previously reported. Neither opioid nor NSAID use was associated with higher risk of macroscopic infarcts or with Lewy body disease. Prescription opioid use is not associated with dementia-related neuropathologic changes, but heavy NSAID use may be. More research is needed examining chronic pain, its pharmacologic treatments, and neuropathologic changes.

Rates of Nonsteroidal Anti-Inflammatory Drug Use in Patients with Established Cardiovascular Disease: A Retrospective, Cross-Sectional Study from NHANES 2009-2010.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, inflammation, and fever in the USA. Unfortunately, NSAIDs have been associated with an increased risk of adverse cardiovascular events, especially among NSAID users with established cardiovascular disease (CVD). In 2005, the Food and Drug Administration (FDA) released an initial warning regarding NSAID use and CVD risk, and recently, in July 2015, released an updated statement strengthening this initial warning. The purpose of this study is to evaluate the rates of NSAID use among patients with CVD following the 2005 FDA warning regarding NSAID use and increased CVD risk. This was a retrospective, cross-sectional study of participants from the National Health and Nutrition Examination Survey, 2009-2010. Participants' CVD status was determined by self-reported diagnosis. Current use of over the counter (OTC) NSAIDs was defined by self-reported use of ibuprofen or naproxen, and we identified the current use of prescription NSAIDs in the database of prescription medication. Respondents with CVD were 2.1 times more likely to use OTC NSAIDs or prescription NSAIDs than respondents without CVD. Among CVD patients, respondents with angina and myocardial infarction were 60% more likely to use any form of NSAID, and respondents with congestive heart failure were less likely to use any form of NSAID than those with other forms of CVD. Our results indicate that there is still a large proportion of CVD patients using NSAIDs. It is now crucial to determine the reasons why prescribers are still prescribing NSAIDs despite the FDA warning.

Associations of NSAID and paracetamol use with risk of primary liver cancer in the Clinical Practice Research Datalink

Liver cancer incidence has been rising rapidly in Western countries. Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are widely-used analgesics that may modulate the risk of liver cancer, but population-based evidence is limited. We conducted a case-control study (1195 primary liver cancer cases and 4640 matched controls) within the United Kingdom’s Clinical Practice Research Datalink to examine the association between the use of prescription NSAIDs and paracetamol and development of liver cancer. Multivariable-adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Overall, ever-use of NSAIDs was not associated with risk of liver cancer (aOR=1.05, 95% CI=0.88–1.24), regardless of recency and intensity of use. Use of paracetamol was associated with a slightly increased risk of liver cancer (aOR=1.18, 95% CI=1.00–1.39), particularly among individuals with body mass index<25kg/m2 (aOR=1.56, 95% CI=1.17–2.09). Our results suggest that NSAID use was not associated with liver cancer risk in this population. Ever-use of paracetamol may be associated with slightly higher liver cancer risk, but results should be interpreted cautiously due to methodological limitations. Given that paracetamol is a widely-used analgesic, further examination of its relationship with liver cancer is warranted.

Effects of prescription nonsteroidal antiinflammatory drugs on symptoms and disease progression among patients with knee osteoarthritis.

The effect of short-term and long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) on structural change is equivocal. The aim of this study was to estimate the extent to which short- and long-term use of prescription NSAIDs relieve symptoms and delay structural progression among patients with radiographically confirmed osteoarthritis (OA) of the knee. We applied a new-user design among participants with confirmed OA not reporting NSAID use at the time of enrollment in the Osteoarthritis Initiative. Participants were evaluated for changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales (n = 1,846) and joint space width was measured using serial radiographs and a customized software tool (n = 1,116) over 4 years. We used marginal structural modeling to estimate the effect of NSAIDs. Compared to participants who never reported prescription NSAID use, those reporting use at 1 or 2 assessments had no clinically important changes, but those reporting prescription NSAID use at all 3 assessments had, on average, 0.88 point improvement over the followup period (95% confidence interval [95% CI] -0.46 to 2.22) in pain, 0.72 point improvement (95% CI -0.12 to 1.56) in stiffness, and 4.27 points improvement (95% CI -0.31 to 8.84) in function. The average change in joint space width was 0.28 mm less among those reporting NSAID use at 3 assessments relative to nonusers (95% CI -0.06 to 0.62). Recent NSAID use findings were not clinically or statistically significant. Long-term, but not short-term, NSAID use was associated with an a priori-defined minimally important clinical change in stiffness, physical function, and joint space width, but not pain. While showing modest clinical importance, the estimates did not reach statistical significance.

Gastrointestinal symptoms in NSAID users in an ‘average risk population’: results of a large population-based study in randomly selected Dutch inhabitants

Non-steroidal anti-inflammatory drug (NSAID) use is widespread and associated with gastrointestinal symptoms and complications. The aims of this study were to assess (i) gastrointestinal symptoms in users of prescribed and over-the-counter (OTC) NSAIDs and (ii) proton pump inhibitor (PPI) co-prescription rates in NSAID users at increased risk for gastrointestinal complications. Surveys were sent to a randomly selected sample of the adult Dutch general population in December 2008. Questions included demographics, gastrointestinal symptoms, medication use and comorbidity. Main outcome measure was presence of gastrointestinal symptoms. A total of 18,317 surveys were returned (response rate 35%), of which 16,758 surveys were eligible for analysis. Of these, 3233 participants (19%) reported NSAID use. NSAID users more frequently reported gastrointestinal symptoms than persons not using NSAIDs (33% vs. 24%, p<0.01). Respondents who specified on prescription NSAID use (n=683) were older, reported more comorbidity, and experienced more gastrointestinal symptoms (41%) compared with OTC users (n=894, 33%, p<0.01). This difference was not statistically significant after adjustment for confounders (0.99, 95% CI 0.71-1.37). In respondents with an increased gastrointestinal risk profile, PPI co-prescription rates were 51% for on prescription users and 25% for OTC users. Prevalence of gastrointestinal symptoms was high in both prescribed and OTC NSAID users, emphasising the side effects of both types of NSAIDs. PPI co-prescription rates in NSAID users at risk for gastrointestinal complication were low.