Osteoporosis is a global problem with an expected increase in f acture prevalence and public health burden as the world s population ages. Although excess mortality is well-described in those with low bone mineral density as well as those with recent hip and vertebral fractures, some uncertainty remains about whether this link is causal. Survival depends greatly on the fracture types, age, gender, and race. Deaths are predominately due to comorbidities, but may also be attributed to the fracture event itself, either directly or indirectly. The goal of osteoporosis care is prevention of fractures and ultimately reduction in morbidity and mortality. Until recently, there have been no data showing that osteoporosis treatment improves mortality, and even now the extent of these data are rather limited. Large observational cohort studies over considerable time are needed to determine whether improving osteoporosis quality of care will improve mortality rates.
Osteoporosis; hip fractures; vertebral fractures; mortality; epidemiology
Administrative claims databases have large samples and high generalizability. They have been used to evaluate associations of atypical subtrochanteric fractures with bisphosphonates. We developed and assessed accuracy of claims-based algorithms with hospital and physician diagnosis codes for these fractures.
Medical records and radiology reports of all adults admitted at University of Alabama at Birmingham Hospital from 2004-2008 with ICD-9 hospital discharges and surgeons' fracture repair codes for subtrochanteric femoral fractures, and random sample of other femoral fractures were reviewed. An expert panel adjudicated any discordance.
We identified 137 persons with suspected subtrochanteric femoral fractures and randomly selected 50 persons with either suspected diaphyseal femoral fractures or hip fractures other than subtrochanteric and diaphyseal femoral fracture (typical hip fracture). Eleven patients had radiographic features indicative of atypical femoral fractures. The positive predictive value (PPV) of claims-based algorithms varied with primary or secondary positions on discharge diagnoses, and the sources of diagnosis codes. The PPV for fractures ranged 69-89% for subtrochanteric femoral, 89-98% for diaphyseal femoral and 85-98% for typical hip fractures. The PPV of administrative codes for defining a femoral fracture as atypical was low and imprecise.
Claims-based algorithms combining hospital discharges with surgeon's diagnosis codes had high PPV to identify the site of subtrochanteric or diaphyseal femoral fractures versus typical hip fractures. However, claims-based data were not accurate in identifying atypical femoral fractures. These claims algorithms will be useful in future population-based observational studies to evaluate associations between osteoporosis medications and subtrochanteric and diaphyseal femoral fractures.
Atypical femoral fracture; Diagnostic Codes; Administrative Claims Data
Predominantly uncontrolled studies suggest that there may be a greater risk of subsequent vertebral compression fractures (VCFs) associated with vertebroplasty and kyphoplasty. To further understand the risk of VCFs, we conducted a population-based retrospective cohort study using data from a large regional health insurer.
Materials and Methods
Administrative claims procedure codes were used to identify a treatment group of patients receiving either a vertebroplasty or kyphoplasty (treatment group) and a comparison group of patients with a primary diagnosis of VCF who did not receive treatment during the same time period. The main outcomes of interest, validated by two independent medical record reviewers and adjudicated by a physician panel, were any new VCFs within: 1) 90-days; 2) 360-days; and 3) at adjacent vertebral levels. Multivariable logistic regression examined the association of vertebroplasty/kyphoplasty with new VCFs.
Among 48 treatment (51% vertebroplasty, 49% kyphoplasty) and 164 comparison patients, treated patients had a significantly greater risk of secondary VCFs than comparison patients for fractures within 90 days of the procedure or comparison group time point (adjusted odds ratio (OR) = 6.3; 95% confidence interval (CI) 1.7 – 23.0) and within 360 days (adjusted OR = 3.1; 95% CI:1.1 – 8.4). Vertebroplasty and kyphoplasty were associated with a significantly greater rate of adjacent-level fractures as well.
Patients who had undergone vertebroplasty and kyphoplasty had a greater risk of new VCFs compared to patients with prior VCFs who did not undergo either procedure.
Although the systematic measurement of disease activity facilitates clinical decision making in rheumatoid arthritis (RA), no recommendations currently exist on which measures should be applied in clinical practice in the US. The American College of Rheumatology (ACR) convened a Working Group (WG) to comprehensively evaluate the validity, feasibility, and acceptability of available RA disease activity measures and derive recommendations for their use in clinical practice.
The Rheumatoid Arthritis Clinical Disease Activity Measures Working Group conducted a systematic review of the literature to identify RA disease activity measures. Using exclusion criteria, input from an Expert Advisory Panel (EAP), and psychometric analysis, a list of potential measures was created. A survey was administered to rheumatologists soliciting input. The WG used these survey results in conjunction with the psychometric analyses to derive final recommendations.
Systematic review of the literature resulted in identification of 63 RA disease activity measures. Application of exclusion criteria and ratings by the EAP narrowed the list to 14 measures for further evaluation. Practicing rheumatologists rated 9 of these 14 measures as most useful and feasible. From these 9 measures, the WG selected 6 with the best psychometric properties for inclusion in the final set of ACR-recommended RA disease activity measures.
We recommend the Clinical Disease Activity Index, Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein), Patient Activity Scale (PAS), PAS-II, Routine Assessment of Patient Index Data with 3 measures, and Simplified Disease Activity Index because they are accurate reflections of disease activity; are sensitive to change; discriminate well between low, moderate, and high disease activity states; have remission criteria; and are feasible to perform in clinical settings.
Pragmatic clinical trials (PCTs) provide large sample sizes and enhanced generalizability to assess therapeutic effectiveness, but efficient patient enrollment procedures are a challenge, especially for community physicians. Advances in technology may improve methods of patient recruitment and screening in PCTs. Our study looked at a tablet computer versus an integrated voice response system (IVRS) for patient recruitment and screening for an osteoporosis PCT in community physician offices.
Materials and methods
We recruited women ≥ 65 years of age from community physician offices to answer screening questions for a hypothetical osteoporosis active comparator PCT using a tablet computer or IVRS. We assessed the feasibility of these technologies for patient recruitment as well as for patient, physician, and office staff satisfaction with the process. We also evaluated the implications of these novel recruitment processes in determining the number of primary care practices and screened patients needed to conduct the proposed trial.
A total of 160 women (80% of those approached) agreed to complete the osteoporosis screening questions in ten family physicians’ offices. Women using the tablet computer were able to complete all screening questions consistently and showed a nonsignificant trend towards greater ease of use and willingness to spend more time in their physician’s office compared to those using IVRS. Using the proportion of women found to be eligible in this study (almost 20%) and other eligibility scenarios, we determined that between 240 and 670 community physician offices would be needed to recruit ample patients for our hypothetical study.
We found good satisfaction and feasibility with a tablet computer interface for the recruitment and screening of patients for a hypothetical osteoporosis PCT in community office settings. In addition, we used this experience to estimate the number of research sites needed for such a study.
osteoporosis; clinical trial; pragmatic clinical trials; computer applications
Large pragmatic clinical trials (PCTs) are increasingly used to conduct comparative effectiveness research. In the context of planning a safety PCT of the live herpes zoster vaccine in rheumatoid arthritis (RA) patients age ≥ 50 receiving anti- tumor necrosis factor (TNF) therapy, we evaluated the use of health plan combined with registry data to assess the feasibility of recruiting the 4,000 patients needed for the trial and to facilitate site selection.
Using national United States data from Medicare, we identified older RA patients who received anti-TNF therapy in the last quarter of 2009. Extrapolations were made from the Medicare patient population to younger patients and those with other types of insurance using the Consortium of Rheumatology Researchers of North America (CORRONA) disease registry. Patients’ treating rheumatologists were grouped into practices and sorted by size from the greatest to the least number of eligible patients.
Approximately 50,000 RA patients receiving anti-TNF therapy were identified in the Medicare data, distributed across 1,980 physician practices. After augmenting Medicare data with information from CORRONA and extrapolating to younger patients and those with other types of insurance, more than 12,000 potentially eligible study subjects were identified from the 40-45 largest rheumatology practices.
Health plan and registry databases appear useful to assess feasibility of large pragmatic trials and to assist in selection of recruitment sites with the greatest number of potentially eligible patients. This novel approach is applicable to trials with simple inclusion/exclusion criteria that can be readily assessed in these data sources.
pragmatic trial; clinical trial; registry; administrative data; recruitment; rheumatoid arthritis; anti-TNF therapy; herpes zoster; shingles
To determine among patients with autoimmune diseases in the United States whether the risk of non-viral opportunistic infections (OIs) was increased among new users of tumor necrosis factor-alpha inhibitors (TNFI), when compared to users of non-biologic agents used for active disease.
We identified new users of TNFI among cohorts of rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis-psoriatic arthritis-ankylosing spondylitis (PsO-PsA-AS) patients during 1998–2007 using combined data from Kaiser Permanente Northern California, two pharmaceutical assistance programs for the elderly, Tennessee Medicaid, and US Medicaid/Medicare programs. We compared incidence of non-viral OIs among new TNFI users and patients initiating non-biologic disease modifying drugs (DMARDs) overall and within each disease cohort. Cox regression models were used to compare propensity-score and steroid- adjusted OI incidence between new TNFI and non-biologic DMARD users.
Within a cohort of 33,324 new TNFI users we identified 80 non-viral OIs, the most common of which was pneumocystosis (n=16). In the combined cohort, crude rates of non-viral OIs among new users of TNFI as compared to those initiating non-biologic DMARDs was 2.7 verus 1.7 per 1000-person years[adjusted hazard ratio (aHR): 1.6, 95% CI: 1.0, 2.6)]. Baseline corticosteroid use was associated with non-viral OIs (aHR 2.5, 95% CI: 1.5, 4.0). In the RA cohort, rates of non-viral OIs among new users of infliximab were higher when compared to patients newly starting non-biologic DMARDs (aHR 2.6, 95% CI 1.2, 5.6) or new etanercept users (aHR 2.9, 95% CI: 1.5, 5.4).
In the US, the rate of non-viral OIs was higher among new users of TNFI with autoimmune diseases as compared to non-biologic DMARD users.
opportunistic infection; tumor necrosis factor-alpha; Pneumocystis; tuberculosis; rheumatoid arthritis
Rheumatologic diseases are associated with a pro-inflammatory state which is thought to lead to many of the bone changes seen in treatment-naive patients. However, glucocorticoids remain a common treatment option for rheumatologic diseases and are known to have a negative impact on bone through direct effects on bone cells and indirect effects on calcium absorption. Despite the anti-inflammatory effect of glucocorticoids, fracture risk rises within the first three months of treatment. As such, osteoporosis prevention and treatment need to be considered in all patients started on chronic glucocorticoids (≥3 months of treatment). For very low risk patients, conservative management with non-pharmacologic strategies may be appropriate. For the moderate to high fracture risk patients treated with glucocorticoids, pharmacologic treatment with one of the four approved medications should be considered. The challenge of educating physicians and patients of the risks of glucocorticoid induced osteoporosis remain.
Osteoporosis; Glucocorticoid; Treatment; Teriparatide; Bisphosphonates; Calcium; Vitamin D; Rheumatoid Arthritis; Lupus; Ankylosing Spondylitis
Gout is a common and disabling cause of arthritis in middle-aged and elderly populations, with its main predisposing factor being hyperuricemia (serum urate > 6.8 mg/dL). Options for treatment of chronic gout until 2008 were allopurinol, a xanthine oxidase inhibitor, and the group of drugs known as uricosurics that stimulate the renal excretion of uric acid. A proportion of patients, including some with chronic kidney disease and solid organ transplantations, could not be treated with the those therapies because of intolerance, drug interactions, or adverse events. Febuxostat is a nonpurine xanthine oxidase inhibitor, recently approved in Europe and the United States for the treatment of chronic gout.
To review the clinical evidence (phase II and III studies) of the effectiveness and safety of febuxostat for treatment of hyperuricemia and gout.
Febuxostat, at doses ranging from 40 to 240 mg/day, is efficacious in reducing serum urate in patients with hyperuricemia and gout, comparing favorably with fixed doses of allopurinol in that respect. Early safety signals with respect to liver test abnormalities and cardiovascular outcomes have not been confirmed in recent large prospective trials but need to be further monitored.
Given its low cost and extensive clinical experience, allopurinol will likely remain the first-line drug for management of hyperuricemia and gout. Febuxostat may provide an important option in patients unable to use allopurinol, those with very high serum urate levels, or in the presence of refractory tophi.
febuxostat; gout; hyperuricemia; evidence
To determine patients’ preferences for, and understanding of, FRAX® fracture risk conveyed through illustrations.
Drawing on examples from published studies, four illustrations of fracture risk were designed and tested for patient preference, ease of understanding, and perceived risk. We enrolled a convenience sample of adults aged 50 and older at two medical clinics located in the Midwestern and Southern United States. In-person structured interviews were conducted to elicit patient ranking of preference, ease of understanding, and perceived risk for each illustration.
Most subjects (n = 142) were female (64%), Caucasian (76%) and college educated (78%). Of the four risk depictions, a plurality of participants (37%) listed a bar graph as most preferred. Subjects felt this illustration used the stoplight color system to display risk levels well and was the most “clear,” “clean,” and “easy to read”. The majority of subjects (52%) rated the pictogram as the most difficult to understand as this format does not allow people to quickly ascertain their individual risk category.
Communicating risk to patients with illustrations can be done effectively with clearly designed illustrations responsive to patient preference.
ClinicalTrials.gov Identifier: NCT01507662
Osteoporosis; DXA Scan; Risk; Fracture; Bone; Patient education
To determine the extent to which OMERACT participants agree that instruments that have been used in clinical trials and measure OMERACT core outcome domains in acute gout fulfil the filter requirements of truth, discrimination and feasibility and to determine where future research efforts need to be directed.
The results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups and opinion was defined by subsequent voting in a plenary session. Endorsement was defined as at least 70% of participants voting in agreement with the proposition (where the denominator excluded those participants who did not vote or who voted ‘don’t know’).
The following measures were endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale and/or VAS (0 to 100mm) to measure pain; (2) 4-point Likert scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4) 5-point Likert scale for patient global assessment of response to treatment. Measures for the activity limitations domain were not endorsed.
Measures of pain, joint swelling, joint tenderness and patient global assessment in acute gout were endorsed at OMERACT-11. These measures should now be used in clinical trials of acute gout.
gout; outcome measures; psychometrics
Western studies suggest that beverages may affect serum urate (SU) levels but data from Asian populations are scarce. We evaluated the associations between beverages and SU levels in Singapore Chinese.
The study population consisted of 483 subjects from the Singapore Chinese Health Study cohort, aged 45-74 years, recruited between 1993 and 1998. Lifestyle factors, medical histories and diet were collected through in-person interviews. SU and other biomarkers were measured from blood collected between 1994 and 1996.
Mean age was 57.6 years and 44% were men. The geometric mean of SU was 321 μmol/L (range 157-719 μmol/L). Mean SU levels increased with alcohol consumption (P for trend = 0.024). The mean SU level of daily alcohol drinkers was 42.6 μmol/L higher than that of non-drinkers. Similarly, increasing frequency of green tea intake was associated with rising SU levels. The highest mean SU level was observed in daily green tea drinkers (difference of 25.0 μmol/L) relative to non-drinkers (P for trend = 0.009). Compared to non-drinkers, daily alcohol drinkers had an almost 5-fold increase in association with hyperuricaemia [odds ratio (OR) = 4.83; 95% confidence interval (CI) = 1.10-21.23) while daily green tea drinkers had a 2-fold increase in association with hyperuricaemia (OR=2.12, 95% CI=1.03-4.36). The present study did not show elevated levels of SU in individuals who consumed black tea, coffee, fruit juice or soda.
Alcohol consumption increases SU levels. The finding that daily drinking of green tea is associated with hyperuricaemia needs validation in future studies.
serum urate; coffee; tea; soft drinks; fruit juice; alcohol; Chinese
Fractures in obese postmenopausal women may be associated with higher morbidity than in non-obese women. We aimed to compare healthcare utilization, functional status, and health-related quality of life (HRQL) in obese, non-obese and underweight women with fractures. Information from GLOW, started in 2006, was collected at baseline and at 1, 2 and 3 years. In this subanalysis, self-reported incident clinical fractures, healthcare utilization, HRQL and functional status were recorded and examined. Women in GLOW (n = 60,393) were aged ≥55 years, from 723 physician practices at 17 sites in 10 countries. Complete data for fracture and body mass index were available for 90 underweight, 3,270 non-obese and 941 obese women with ≥1 incident clinical fracture during the 3-year follow-up. The median hospital length of stay, adjusted for age, comorbidities and fracture type, was significantly greater in obese than non-obese women (6 vs. 5 days, P = 0.017). Physical function and vitality score were significantly worse in obese than in non-obese women, both before and after fracture, but changes after fracture were similar across groups. Use of anti-osteoporosis medication was significantly lower in obese than in non-obese or underweight women. In conclusion, obese women with fracture undergo a longer period of hospitalization for treatment and have poorer functional status and HRQL than non-obese women. Whether these differences translate into higher economic costs and adverse effects on longer-term outcomes remains to be established.
Fractures; Healthcare utilization; Functional status; Quality of life; Obesity
Purpose of review
To summarize the recent literature concerning the role of TNF-a in heart failure, epidemiology of heart failure in rheumatoid arthritis and risk of heart failure associated with biologic disease-modifying antirheumatic drugs in rheumatoid arthritis.
TNF-a has been implicated in the pathogenesis of heart failure. It has direct deleterious effects on the myocardium in the setting of acute injury or chronic heart failure. In animal models, TNF-a is important in cardiac remodeling, leading to cardiac dysfunction following acute injury. Both incident and worsening heart failure have been reported in patients with rheumatoid arthritis who are treated with anti-TNF-a therapy. Recent cohort studies, however, have shown no increased risk and, in some, a protective effect on the risk of heart failure. Certain traditional cardiovascular risk factors have a relatively lesser contribution to cardiovascular morbidity and mortality in patients with rheumatoid arthritis, suggesting that disease-related perturbations of the cytokine network may contribute to the excess risk of heart failure in these patients.
Overall mortality in rheumatoid arthritis has remained stagnant despite advances in rheumatoid arthritis and heart failure management and improved cardiovascular mortality in the general population. Heart failure prevalence is increased in patients with rheumatoid arthritis and leads to greater mortality. Despite current expert consensus contraindicating the use of anti-TNF-a agents in patients with moderate to severe heart failure, epidemiological studies in rheumatoid arthritis have not consistently substantiated this association.
anti-TNF-a agents; biologic disease-modifying antirheumatic drugs; heart failure; rheumatoid arthritis
To test an evidence-implementation intervention to improve the quality of care in the home health care setting for patients at high risk for fractures.
We conducted a cluster randomized trial of a multimodal intervention targeted at home care for high-risk patients (prior fracture or physician-diagnosed osteoporosis) receiving care in a statewide home health agency in Alabama. Offices throughout the state were randomized to receive the intervention or to usual care. The primary outcome was the proportion of high-risk home health patients treated with osteoporosis medications. A t-test of difference in proportions was conducted between intervention and control arms and constituted the primary analysis. Secondary analyses included logistic regression estimating the effect of individual patients being treated in an intervention arm office on the likelihood of a patient receiving osteoporosis medications. A follow-on analysis examined the effect of an automated alert built into the electronic medical record that prompted the home health care nurses to deploy the intervention for high risk patients using a pre-post design.
Among the offices in the intervention arm the average proportion of eligible patients receiving osteoporosis medications post-intervention was 19.1%, compared with 15.7% in the usual care arm (difference in proportions 3.4%, 95% CI: −2.6 −9.5%). The overall rates of osteoporosis medication use increased from 14.8% prior to activation of the automated alert to 17.6% afterward, a non-significant difference.
The home health intervention did not result in a significant improvement in use of osteoporosis medications in high risk patients.
Osteoporosis; Home Care Services; Quality Improvement; Secondary Prevention
Rheumatoid arthritis; Treatment; recommendations; American College of Rheumatology; Biologics; DMARD; Disease-modifying anti-rheumatic drug
To use a mixed-methods approach to develop a letter that can be used to notify patients of their bone mineral density (BMD) results by mail that may activate patients in their bone-related health care.
Patients and methods
A multidisciplinary team developed three versions of a letter for reporting BMD results to patients. Trained interviewers presented these letters in a random order to a convenience sample of adults, aged 50 years and older, at two different health care systems. We conducted structured interviews to examine the respondents’ preferences and comprehension among the various letters.
A total of 142 participants completed the interview. A majority of the participants were female (64.1%) and white (76.1%). A plurality of the participants identified a specific version of the three letters as both their preferred version (45.2%; P<0.001) and as the easiest to understand (44.6%; P<0.01). A majority of participants preferred that the letters include specific next steps for improving their bone health.
Using a mixed-methods approach, we were able to develop and optimize a printed letter for communicating a complex test result (BMD) to patients. Our results may offer guidance to clinicians, administrators, and researchers who are looking for guidance on how to communicate complex health information to patients in writing.
osteoporosis; DXA; test results; patient education; fracture risk; patient activation
We developed and tested a multi-modal intervention, delivered in the home health care setting, aimed at increasing osteoporosis treatment rates to prevent fractures.
Material and Methods
The intervention focused on home health nurses. Key components included: nursing education; development of a nursing care plan; patient teaching materials and creation of physician materials. Nursing education consisted of a lecture covering osteoporosis, fracture risks and prevention, and the effectiveness of anti-osteoporosis treatment options. Patients received education materials concerning osteoporosis and anti-osteoporosis medications. A pocket-sized treatment algorithm card and standardized order sets were prepared for physicians. Focus groups of physicians and nurses were conducted to obtain feedback on the materials and methods to facilitate effective nurse-physician communication. Successful application required nurses to identify patients with a fracture history, initiate the care plan, prompt physicians on risk status, and provide patient education. The intervention was piloted in one field office.
In the year prior to the intervention, home health patients (n=92) with a fracture history were identified in the pilot field office and only 20 (22%) received osteoporosis prescription therapy. In the three months following the intervention, 21 newly enrolled patients were identified and 9 (43%) had received osteoporosis prescription medications.
Home health care provides a venue where patients and physicians can be informed by nurses about osteoporosis and fracture risks and, consequently, initiate appropriate therapy. This multi-modal intervention is easily transportable to other home health agencies and adaptable to other medical conditions and settings.
osteoporosis; home health; fracture; dissemination; cluster randomized trial; patient education
To compare incidence rates of selected opportunistic infections (OI) among children with and without juvenile idiopathic arthritis (JIA).
Using United States national Medicaid administrative claims data from 2000 through 2005, we identified a cohort of children with JIA based on physician diagnosis codes and dispensed medications. We defined a non-JIA comparator cohort of children diagnosed with attention deficit hyperactivity disorder (ADHD). We defined 15 types of OI using physician diagnosis or hospital discharge codes, and 7 of these types also required evidence of treatment with specific antimicrobials. We calculated infection incidence rates (IR). The rates in the ADHD comparator cohort were standardized to the age, sex, and race distribution of the JIA cohort. We calculated incidence rate ratios (IRR) to compare infection rates.
The JIA cohort included 8,503 children with 13,990 person-years (p-y) of follow-up. The ADHD comparator cohort included 360,362 children with 477,050 p-y of follow-up. When all OI were considered together as a single outcome, there were 42 infections in the JIA cohort (IR 300 per 100,000 p-y; IRR 2.4 [1.7–3.3] versus ADHD). The most common OI among children with JIA were 3 Coccidioides (IR 21 per 100,000 p-y; IRR 101 [8.1–5319] versus ADHD); 5 Salmonella (IR 35 per 100,000 p-y; IRR 3.8 [1.2–9.5]); and 32 herpes zoster (IR 225 per 100,000 p-y; IRR 2.1 [1.4–3.0]).
OI are rare among children with JIA. Nevertheless, children with JIA had a higher rate of OI, including Coccidioides, Salmonella, and herpes zoster, than children with ADHD.
Anti-TNF-α agents have been hypothesized to increase the risk of interstitial lung disease (ILD), including its most severe manifestation, pulmonary fibrosis.
We conducted a cohort study among autoimmune disease patients who were members of Kaiser Permanente Northern California, 1998–2007. We obtained therapies from pharmacy data and diagnoses of ILD from review of X-ray and computed tomography reports. We compared new users of anti-TNF-α agents to new users of non-biologic therapies using Cox proportional hazards analysis to adjust for baseline propensity scores and time-varying use of glucocorticoids. We also made head-to-head comparisons between anti-TNF-α agents.
Among the 8,417 persons included in the analysis, 38 (0.4%) received a diagnostic code for ILD by the end of follow-up, including 23 of 4,200 (0.5%) who used anti-TNF-α during study follow-up, and 15 of 5,423 (0.3%) who used only non-biologic therapies. The age- and gender-standardized incidence rate of ILD, per 100 person-years, was 0.21 (95% CI 0–0.43) for rheumatoid arthritis and appreciably lower for other autoimmune diseases. Compared to use of non-biologic therapies, use of anti-TNF-α therapy was not associated with a diagnosis of ILD among RA patients (adjusted hazard ratio, 1.03; 95% CI 0.51–2.07). Nor did head-to-head comparisons across anti-TNF-α agents suggest important differences in risk, although the number of cases available for analysis was limited.
The study provides evidence that compared to non-biologic therapies anti-TNF-α therapy does not increase the occurrence of ILD among patients with autoimmune diseases, and informs research design of future safety studies of ILD.
Rheumatoid arthritis; psoriatic arthritis; psoriasis; Crohn’s Disease; ulcerative colitis; inflammatory bowel disease; pharmacoepidemiology; drug safety; drug toxicity; adverse events; cohort studies; propensity scores; automated healthcare data; interstitial lung disease; pulmonary fibrosis
To evaluate whether rates of serious infection with anti-TNF therapy in rheumatoid arthritis (RA) patients differ in magnitude by specific drugs and patient characteristics.
Among new non-biologic disease modifying anti-rheumatic drug (DMARD) users enrolled in Medicare/Medicaid or a large U.S. commercial health plan, we created and validated a person-specific infection risk score based upon age, demographics, insurance, glucocorticoid dose, and comorbidities to identify patients at high risk for hospitalized infections. We then applied this risk score to new users of infliximab, etanercept, and adalimumab and compared the observed one-year rate of infection to each other and to the predicted infection risk score estimated in the absence of anti-TNF exposure.
Among 11,657 RA patients initiating anti-TNF therapy, the observed one year rate of infection was 14.2 per 100 person-years in older patients (>= 65 years) and 4.8 in younger patients (< 65 years). There was a relatively constant rate difference of 1–4 infections per 100 person-years associated with anti-TNF therapy across the range of the infection risk score. Infliximab had a significantly greater adjusted rate of infection compared to etanercept and adalimumab in both high and lower risk RA patients.
The rate of serious infections for anti-TNF agents was incrementally increased by a fixed absolute difference irrespective of age, comorbidities, and other factors that contributed to infections. Older patients and those with high comorbidity burdens should be reassured that the magnitude of incremental risk with anti-TNF agents is not greater for them than for lower risk patients.
rheumatoid arthritis; infection; anti-TNF; DMARD; prediction
Osteoporosis; DXA Scan; Patient Education; Fracture, Bone; Letter; Medication Adherence
We compared the incidence of cancer following tumor necrosis factor alpha antagonists (TNF-I) therapy to that with commonly used alternative therapies across multiple immune mediated diseases.
The Safety Assessment of Biologic thERapy (SABER) study used data from national Medicaid & Medicare, Kaiser Permanente Northern California, TennCare, and pharmacy benefits plans for Medicare beneficiaries in New Jersey and Pennsylvania. Propensity score adjusted hazard ratios (HR) and 95% confidence intervals (CI) were computed to estimate the relative rates of cancer, comparing TNF-I users to alternative disease modifying therapies. The cancer finding algorithm had a positive predictive value ranging from 31% for any leukemia to 89% for female breast cancer.
We included 29,555 patients with rheumatoid arthritis (13,102 person-years), 6,357 patients with inflammatory bowel disease (1,508 person-years), 1,298 patients with psoriasis (371 person-years), and 2,498 patients with psoriatic arthritis (618 person-years). The incidence of any solid cancer was not elevated in rheumatoid arthritis (HR 0.80, CI 0.59-1.08), inflammatory bowel disease (HR 1.42, CI 0.47-4.26), psoriasis (HR 0.58, CI 0.10-3.31) or psoriatic arthritis (HR 0.74, CI 0.20-2.76) during TNF-I therapy compared to disease specific alternative therapy. Among patients with rheumatoid arthritis, the incidence of any of the ten most common cancers in the United States and nonmelanoma skin cancer was not increased with TNF-I therapy compared to methotrexate failure.
Short-term cancer risk was not elevated among patients treated with TNF-I therapy relative to commonly used therapies for immune mediated chronic inflammatory diseases in this study.
rheumatoid arthritis; inflammatory bowel disease; psoriasis; psoriatic arthritis; ankylosing spondylitis; tumor necrosis factor alpha
To examine when, where and how fractures occur in postmenopausal women.
We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3.
Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68–86% of NHNV and 68–83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling.
In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.
Prior observational studies have shown an association between bisphosphonate adherence and fewer fractures. It is unclear if such studies reflect pharmacologic benefits or behavioral attributes, i.e. the healthy adherer effect.
To examine the association of therapy adherence and fracture risk among patients initiating therapies hypothesized to be favorable, unfavorable, or neutral toward fracture risk so as to evaluate for a healthy adherer effect.
In this observational study, we identified patients within Medicare 2006-09 data who initiated any of three medication groups within nine months after an osteoporotic fracture: 1) oral bisphosphonates (n = 2507), 2) selective serotonin reuptake inhibitors (SSRI) (n=2420), or 3) angiotensin converting enzyme inhibitor, or calcium channel blocker (ACE/CCB) (n=2178). Cox regression analysis, adjusting for covariates, was used to compare fracture rates at the hip and major osteoporotic fracture sites including hip, clinical vertebral, humerus, and wrist during follow-up comparing patients with high adherence versus low adherence within each medication group.
There were few baseline differences between those who had high adherence versus lower adherence. High adherence with bisphosphonates decreased fracture risk at both hip (hazard ratio (HR) =0.53, 95% CI 0.32-0.96) and major fracture sites (HR = 0.61, 0.45-0.80). High adherence with SSRIs suggested increased fracture risk at both hip (HR = 1.58, 0.97-2.57) and major fracture sites (HR=1.32, 0.96-1.83). High adherence with ACE/CCBs was neutral toward fracture risk at both hip (HR = 1.27, 0.67-2.41) and major fracture sites (HR = 1.00, 0.67-1.49).
In this observational cohort of older individuals, the association between medication adherence and fracture risk differed by medication exposure, suggesting a limited role for the healthy adherer effect in observational studies of osteoporosis medications.
osteoporosis; adherence; persistence; fracture; selective serotonin reuptake inhibitor; bisphosphonates; effectiveness