Associations among temporal and large artery abnormalities on vascular ultrasound in giant cell arteritis.

Objectives: Giant cell arteritis (GCA) can manifest in cranial and/or extracranial arteries. We investigated the distribution of affected arteries on vascular ultrasound (VUS) among patients with new-onset or prior-onset GCA.Method: We retrospectively studied patients with either new-onset or prior-onset GCA and an abnormal VUS, from 2013 to 2017. Trained vascular technologists imaged the bilateral temporal arteries and carotid, axillary, and subclavian arteries. Vascular medicine physicians interpreted the images. Vasculitis-related abnormalities in individual vessels and their distribution (temporal artery, large artery, or both) were evaluated. Phi coefficients (φ) and Fisher's exact test were used to assess correlations among individual abnormal arteries.Results: Among 66 GCA patients, 28.8% had prior-onset GCA (median duration 17.8 months). Acute arteritis on VUS was observed in the majority of patients with both new-onset (72.3%) and prior-onset GCA (68.4%); the remainder had hyperechoic wall thickening without acute arteritis. Involvement of the temporal arteries only (45.5%) or large arteries only (34.8%) was more common than involvement of both (19.7%); this finding was similar in new-onset and prior-onset GCA. There were moderate positive correlations among temporal artery branches (φ = 0.51-0.58, p < 0.003) and among axillary and subclavian arteries (φ = 0.51-0.77, p < 0.003), and moderate negative correlations between abnormalities in the temporal and large arteries (φ = -0.46 to -0.58, p < 0.003).Conclusion: On VUS, vasculitis-related abnormalities in the temporal arteries only or large arteries only were more common than concurrent temporal and large artery abnormalities in patients with both new-onset GCA and prior-onset GCA.

Healing of erosions in rheumatoid arthritis remains elusive: results with 24 months of the anabolic agent teriparatide.

Objective: Erosion healing in rheumatoid arthritis (RA) is difficult to demonstrate. This extension study aimed to determine whether 2 years of teriparatide (TPTD) produces erosion healing. Method: Subjects in a previous 12 month randomized controlled trial of TPTD in RA were invited to receive 12 additional months of open-label TPTD. Eleven of the 24 original subjects were enrolled in the extension study, six of whom received TPTD in the final 12 months only. Subjects receiving 24 months of TPTD were assessed for reduction in erosion volume from baseline using computed tomography. We also compared erosion volumes between 12 and 24 months of TPTD. Large erosions in subjects receiving TPTD for 24 months were examined for volume change. Results: In the six patients who received 24 months of TPTD, there was no significant change in erosion volume at the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints compared with baseline. The six subjects who received 24 months of TPTD had similar changes in erosion volume to the five who received 12 months of TPTD, in MCP (p = 0.17) and PIP (p = 0.63) joints. Assessment of large erosions in those receiving TPTD for 24 months showed no evidence of erosion healing. Conclusion: While this extension study was too small to be conclusive, we observed no evidence of reduction in erosion volume with the addition of TPTD for 24 months in subjects with RA in whom disease activity was controlled on a tumour necrosis factor inhibitor. This is consistent with our negative findings at 12 months.

Patterns of prescription opioid use before total hip and knee replacement among US Medicare enrollees.

OBJECTIVE: To examine patterns of prescription opioid use before total joint replacement (TJR) and factors associated with continuous use of opioids before TJR. DESIGN: We conducted an observational cohort study among Medicare enrollees aged ≥65 years who underwent TJR between 2010 and 2014. Preoperative opioid use was defined as having any opioid prescription in the 12-month period before TJR. Patients who had an opioid prescription every month for a 12-month period were defined as continuous users. We examined patients' demographics, pain-related conditions, medication use, other comorbidities, healthcare utilization and their association with use of opioids before TJR. RESULTS: A total of 473,781 patients underwent TJR:,155,516 THR and 318,265 TKR. Among the total cohort, 60.2% patients had any use of opioids and of those, 12.4% used opioids at least once a month continuously over the 12-month baseline period. Correlates of continuous opioid use included African American race (OR = 2.14, 95% confidence intervals (CI) = 2.01-2.28, compared to White patients), history of drug abuse (OR = 5.18, 95% CI = 3.95-6.79) and back pain (OR = 2.32, 95% CI = 2.24-2.39). CONCLUSIONS: In this large cohort of patients undergoing TJR, over 60% ever used opioids and 12.4% of them continuously used opioids in the 12-month prior to surgery. Utilization of opioids became more frequent and high-dosed near the surgery. History of drug abuse, back pain, and African American race were strongly associated with continuous use of opioids preoperatively. Further research is needed to determine short-term and long-term risks of preoperative use of opioids in TJR patients and to optimize pre- and post-TJR pain management of patients with arthritis.

Intervals between bone mineral density testing with dual-energy X-ray absorptiometry scans in clinical practice.

Intervals between dual-energy X-ray absorptiometry (DXA) scans were evaluated in a large cohort of typical clinical practice. Intensive DXA scanning (intervals < 23 months) decreased substantially, from 16.7% in 2006 to 6.7% in 2015. INTRODUCTION: Serial dual-energy X-ray absorptiometry (DXA) measurements are suggested for patients at high risk of fractures. However, little is known about how often DXA testing occurs in clinical practice. METHODS: We examined time intervals between DXA testing for monitoring purpose at two academic medical centers in the US between 2004 and 2017. The primary outcome was the presence of testing intervals < 23 months (termed "intensive DXA testing"). A generalized linear mixed model was used to evaluate the association between selected patient-level clinical factors and intensive DXA testing. RESULTS: Forty-nine thousand four hundred ninety-four DXA tests from 20,200 patients were analyzed. The mean time interval between scans was 36 ± 21 months. Only 11.1% of the repeated DXA testing met the criterion for intensive testing. The percentage of intensive DXA testing dropped from 16.7% in 2006 to 6.7% in 2015 (p for trend < 0.001). After adjusting for age, gender, number of outpatient visits, and calendar year, correlates of intensive DXA testing included a baseline T-score < -2.5 at any anatomic site (OR, 4.8; 95%CI, 4.0-5.7), active use of drugs for osteoporosis (OR, 1.6; 95%CI, 1.3-1.9), and active use of glucocorticoids (OR, 1.3; 95%CI, 1.2-1.4). CONCLUSIONS: The predictors of intensive DXA testing suggest that this practice is used preferentially in patients with multiple risk factors and to monitor the response to pharmacotherapy. However, intensive DXA testing has become less common in real-world clinical practice over the last decade. Further studies are required to better define the optimal use of bone mineral density testing in this vulnerable population.

Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial.

AIM: To evaluate GI safety of celecoxib compared with 2 nonselective (ns) NSAIDs, as a secondary objective of a large trial examining multiorgan safety. METHODS: This randomised, double-blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100-200 mg b.d., ibuprofen 600-800 mg t.d.s. or naproxen 375-500 mg b.d. plus esomeprazole, and low-dose aspirin or corticosteroids if already prescribed. Clinically significant GI events (CSGIE-bleeding, obstruction, perforation events from stomach downwards or symptomatic ulcers) and iron deficiency anaemia (IDA) were adjudicated blindly. RESULTS: Mean treatment and follow-up durations were 20.3 and 34.1 months. While on treatment or 30 days after, CSGIE occurred in 0.34%, 0.74% and 0.66% taking celecoxib, ibuprofen and naproxen. Hazard ratios (HR) were 0.43 (95% CI 0.27-0.68, P = 0.0003) celecoxib vs ibuprofen and 0.51 (0.32-0.81, P = 0.004) vs naproxen. There was also less IDA on celecoxib: HR 0.43 (0.27-0.68, P = 0.0003) vs ibuprofen; 0.40 (0.25-0.62, P < 0.0001) vs naproxen. Even taken with low-dose aspirin, fewer CSGIE occurred on celecoxib than ibuprofen (HR 0.52 [0.29-0.94], P = 0.03), and less IDA vs naproxen (0.42 [0.23-0.77, P = 0.005]). Corticosteroid use increased total GI events and CSGIE. H. pylori serological status had no influence. CONCLUSIONS: Arthritis patients taking NSAIDs plus esomeprazole have infrequent clinically significant gastrointestinal events. Co-prescribed with esomeprazole, celecoxib has better overall GI safety than ibuprofen or naproxen at these doses, despite treatment with low-dose aspirin or corticosteroids.

The effect of insulin on bone mineral density among women with type 2 diabetes: a SWAN Pharmacoepidemiology study.

This was a longitudinal study examining the effects of insulin use on bone mineral density loss. Insulin use was found to be associated with greater bone mineral density loss at the femoral neck among women with diabetes mellitus. INTRODUCTION: Women with diabetes mellitus (DM) have higher bone mineral density (BMD) and experience slower BMD loss but have an increased risk of fracture. The data regarding the effect of insulin treatment on BMD remains conflicted. We examined the impact of insulin initiation on BMD. METHODS: We investigated the annual changes in BMD associated with the new use of insulin among women with DM in the Study of Women's Health Across the Nation (SWAN). Propensity score (PS) matching, which is a statistical method that helps balance the baseline characteristics of women who did and did not initiate insulin, was used. Covariates with a potential impact on bone health were included in all models. Mixed model regression was used to test the change in BMD between the two groups. Median follow-up time was 5.4 years. RESULTS: The cohort consisted of 110 women, mean age, 53.6 years; 49% white and 51% black. Women using insulin (n = 55) were similar on most relevant characteristics to the 55 not using insulin. Median diabetes duration for the user group was 10 vs. 5.0 years for the non-user group. There was a greater loss of BMD at the femoral neck among insulin users (- 1.1%) vs non-users (- 0.77%) (p = 0.04). There were no differences in BMD loss at the spine - 0.30% vs - 0.32% (p = 0.85) or at the total hip - 0.31% vs - 0.25 (p = 0.71), respectively. CONCLUSIONS: Women with T2DM who initiated insulin experienced a more rapid BMD loss at the femoral neck as compared to women who did use insulin.

Effects of Teriparatide on Joint Erosions in Rheumatoid Arthritis: A Randomized Controlled Trial.

OBJECTIVE: Articular erosions correlate with disability in rheumatoid arthritis (RA). Biologic agents reduce erosion progression in RA, but erosion healing occurs infrequently. This study was undertaken to assess the effects of the anabolic agent teriparatide on joint erosion volume in RA patients treated with a tumor necrosis factor inhibitor (TNFi). METHODS: We conducted a randomized controlled trial in 24 patients with erosive RA, osteopenia, and disease activity controlled by TNFi treatment for at least 3 months. Half were randomized to receive teriparatide for 1 year and the others constituted a wait-list control group. Subjects and primary rheumatologists were not blinded with regard to treatment assignment, but all outcomes were assessed in a blinded manner. The primary outcome measure was change in erosion volume determined by computed tomography at 6 anatomic sites. Significance within each hand and anatomic site was based on a 2-tailed test, with P values less than 0.05 considered significant. RESULTS: Baseline characteristics of the treatment groups were well balanced. After 52 weeks, the median change in erosion volume in the teriparatide group was -0.4 mm3 (interquartile range [IQR] -34.5, 29.6) and did not differ significantly from that in controls (median change +9.1 mm3 [IQR -29.6, 26.4]) (P = 0.28). No significant difference in change in erosion volume was noted at the radius, ulna, or metacarpophalangeal joints. Bone mineral density improved at the femoral neck and lumbar spine in the teriparatide group. CONCLUSION: Our findings indicate that teriparatide treatment for 1 year does not significantly reduce erosion volume in the hands or wrists of patients with established RA with disease activity controlled by TNFi treatment.

Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving hydroxychloroquine alone.

Factors associated with fractures in HIV-infected persons: which factors matter?

This study aims to determine what factors are associated with increased risk of fracture among patients with HIV, in particular whether an important medication used to treat HIV, tenofovir, is associated with fracture. Our study found that while co-infection with hepatitis C and markers of HIV severity were associated with fracture, tenofovir was not. INTRODUCTION: Growing evidence suggests that tenofovir disoproxil fumarate decreases bone density among patients with HIV, but there are conflicting reports as to whether this decrease in bone density translates to higher fracture risk. We aimed to determine what factors were associated with an increased risk of fracture for patients with HIV, in particular whether tenofovir is associated with elevated fracture risk. METHODS: We conducted a retrospective cohort study at two tertiary care hospitals in Boston, MA, between 2001 and 2012 to determine whether tenofovir use is associated with elevated all-site fracture risk, as compared to other antiretroviral medications. We also examined other potential factors associated with fracture among patients with HIV. RESULTS: We identified 1981 HIV-infected patients who had at some point used tenofovir and 682 patients who had not. The mean age was 43 years, and 72 % were male. The hepatitis C co-infection rate was 28 %, about 40 % had nadir CD4 count <200, and about 40 % had a history of an AIDS-defining illness. We did not find an association between risk of fracture and tenofovir disoproxil fumarate (TDF) (adjusted RR (aRR) 0.8, 95 % CI 0.6-1.1). However, co-infection with hepatitis C did increase risk of fracture (aRR 1.6, 95 % CI 1.1-2.3), as did nadir CD4 count <200 (aRR 3.1, 95 % CI 1.9-5.0) and history of AIDS-defining illness (aRR 1.6, 95 % CI 1.1-2.2). CONCLUSION: There was no association found between fracture and tenofovir use, but there were associations between co-infection with hepatitis C and markers of advanced HIV disease and fracture.

Cost-effectiveness of nonsteroidal anti-inflammatory drugs and opioids in the treatment of knee osteoarthritis in older patients with multiple comorbidities.

OBJECTIVE: To evaluate long-term clinical and economic outcomes of naproxen, ibuprofen, celecoxib or tramadol for OA patients with cardiovascular disease (CVD) and diabetes. DESIGN: We used the Osteoarthritis Policy Model to examine treatment with these analgesics after standard of care (SOC) - acetaminophen and corticosteroid injections - failed to control pain. NSAID regimens were evaluated with and without proton pump inhibitors (PPIs). We evaluated over-the-counter (OTC) regimens where available. Estimates of treatment efficacy (pain reduction, occurring in ∼57% of patients on all regimens) and toxicity (major cardiac or gastrointestinal toxicity or fractures, risk ranging from 1.09% with celecoxib to 5.62% with tramadol) were derived from published literature. Annual costs came from Red Book Online(®). Outcomes were discounted at 3%/year and included costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs). Key input parameters were varied in sensitivity analyses. RESULTS: Adding ibuprofen to SOC was cost saving, increasing QALYs by 0.07 while decreasing cost by $800. Incorporating OTC naproxen rather than ibuprofen added 0.01 QALYs and increased costs by $300, resulting in an ICER of $54,800/QALY. Using prescription naproxen with OTC PPIs led to an ICER of $76,700/QALY, while use of prescription naproxen with prescription PPIs resulted in an ICER of $252,300/QALY. Regimens including tramadol or celecoxib cost more but added fewer QALYs and thus were dominated by several of the naproxen-containing regimens. CONCLUSIONS: In patients with multiple comorbidities, naproxen- and ibuprofen-containing regimens are more effective and cost-effective in managing OA pain than opioids, celecoxib or SOC.

Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study.

SUMMARY: We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women's Health Across the Nation. Thiazide users had a slower decline in BMD compared to nonusers, while decline among ACE inhibitor and beta blocker users were similar to rates in nonusers. INTRODUCTION: Several blood pressure lowering drugs may affect bone mineral density (BMD), leading to altered fracture risk. We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women's Health Across the Nation. METHODS: We conducted a propensity score matched cohort study. Women were initiators of ACE inhibitors (ACEi), beta-blockers (BB), or thiazide diuretics (THZD). Their annualized BMD changes during the 14 years of observation were compared with nonusers. RESULTS: Among the 2312 eligible women, we found 69 ACEi, 71 BB, and 74 THZD users who were matched by a propensity score with the same number of nonusers. THZD users had a slower annual percent decline in BMD compared to nonusers at the femoral neck (FN) (-0.28% vs -0.88%; p = 0.008) and the spine (-0.74% vs -1.0%; p = 0.34), albeit not statistically significant. Annual percent changes in BMD among ACEi and BB users were similar to rates in nonusers. In comparison with BB, THZD use was associated with a trend toward less annualized BMD loss at the spine (-0.35% vs -0.60%; p = 0.08) and a similar trend at the FN (-0.39% vs -0.64%; p = 0.08); in comparisons with ACEi, THZD was also associated with less loss at the FN (-0.48% vs -0.82%; p = 0.02), but not at the spine (-0.40% vs -0.56%; p = 0.23). CONCLUSIONS: Neither ACEi nor BB was associated with improvements in BMD. THZD use was associated with less annualized loss of BMD compared with nonusers, as well as compared with ACEi and BB.

Derivation and internal validation of an expanded cardiovascular risk prediction score for rheumatoid arthritis: a Consortium of Rheumatology Researchers of North America Registry Study.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of mortality in rheumatoid arthritis (RA), but CV risk prediction scores derived from the general population do not accurately predict CV risk in RA patients. The goal of these analyses was to develop and internally validate an expanded CV risk prediction score for RA. METHODS: Study participants were patients with RA and no known CVD from the Consortium of Rheumatology Researchers of North America registry. Two-thirds of the cohort were used to derive the CV risk prediction score, and one-third for internal validation. Traditional CV risk factors were included in the base Cox regression model, and RA-related variables were assessed in an expanded model predicting confirmed CV events. Fit and utility of the expanded model were evaluated. RESULTS: The study cohort included 23,605 RA patients with 437 CV events over a median followup of 2.2 years. The RA variables found to be significant in the regression models and included in the expanded risk model were disease activity (Clinical Disease Activity Index >10 versus ≤10), disability (modified Health Assessment Questionnaire disability index >0.5 versus ≤0.5), daily prednisone use (any versus none), and disease duration (≥10 years versus <10 years). The expanded model had good fit (Hosmer-Lemeshow goodness of fit P = 0.94) and a lower Akaike's information criterion than the base model. In the internal validation cohort, the c-statistic for model discrimination was significantly improved from the base model to the expanded model (from 0.7261 to 0.7609; P = 0.0104). The net reclassification index of CV risk in models using a 4-category CV risk prediction tool was 40% (95% confidence interval 37-44%). CONCLUSION: This newly developed, expanded risk score for CV outcomes in RA performs well and improves the classification of CV risk in comparison to a risk prediction score in which only traditional risk factors were included.

Disease activity in rheumatoid arthritis and the risk of cardiovascular events.

OBJECTIVE: Use of several immunomodulatory agents has been associated with reduced numbers of cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown whether time-averaged disease activity in RA correlates with CV events. METHODS: We studied patients with RA whose cases were followed in a longitudinal US-based registry. Time-averaged disease activity was assessed during followup using the area under the curve of the Clinical Disease Activity Index (CDAI), a validated measure of RA disease activity. Age, sex, presence of diabetes mellitus, hypertension, or hyperlipidemia, body mass index, family history of myocardial infarction (MI), use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), presence of CV disease, and baseline use of an immunomodulator were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV end point that included MI, stroke, and death from CV causes. RESULTS: A total of 24,989 patients who had been followed up for a median of 2.7 years were included in these analyses. During followup, we observed 534 confirmed CV end points, for an incidence rate of 7.8 per 1,000 person-years (95% confidence interval [95% CI] 6.7-8.9). In models adjusted for variables noted above, a 10-point reduction in the time-averaged CDAI was associated with a 21% reduction in CV risk (95% CI 13-29). These results were robust in subgroup analyses stratified by the presence of CV disease, use of corticosteroids, use of NSAIDs or selective cyclooxygenase 2 inhibitors, and change in RA treatment, as well as when restricted to events adjudicated as definite or probable. CONCLUSION: Our findings showed that reduced time-averaged disease activity in RA is associated with fewer CV events.

Patterns of treatment among a cohort of older low-income adults starting new medications for osteoporosis.

UNLABELLED: Among 125,954 new users of osteoporosis (OP) medications, 77 % of subjects stopped OP medications, and 23 % of subjects added or started a new OP medication during follow-up, with the first addition or start of a new OP medication occurring in a mean of 739 days after original OP treatment. INTRODUCTION: We described patterns and predictors of OP medication use, focusing on treatment changes over time. METHODS: We analyzed health and pharmacy insurance claims for a large cohort of low-income Medicare beneficiaries with a drug benefit for the years 1998-2008. Study subjects had documented Medicare claims and no receipt of OP medications (i.e., bisphosphonate, raloxifene, calcitonin, teriparatide, or hormonal therapy) during a baseline of 180 days. Subjects were then required to start an OP medication. Baseline patient and prescriber characteristics were assessed in multivariable Cox regression models to identify correlates of adding or starting a new OP medication. Fractures, bone mineral density testing, and visits with endocrinologists or rheumatologists occurring after baseline were also examined as correlates. RESULTS: We included 125,954 new users of OP medications with a mean age of 78 years, 97 % female, and 92 % white. OP medication prescribers included specialists (i.e., endocrinologists or rheumatologists) (6.2 %), orthopedic surgeons (1.0 %), primary care providers (64.9 %), other physicians (3.7 %), and missing (24.1 %). Seventy-seven percent of subjects stopped OP medications, and 23 % of subjects added or started a new OP medication during follow-up, with the first addition or start of a new OP medication occurring in a mean of 739 days after original OP treatment; 4 % added or started a new OP medication more than once. In fully adjusted models, many baseline variables correlated with starting a second OP medication. Post-baseline fractures [hazard ratio (HR) 1.76, 95 % confidence interval (CI) 1.71-1.82] and bone mineral density testing (HR 2.94, 95 % CI 2.86-3.03) were strong predictors. CONCLUSION: Approximately one quarter of patients starting an OP medication added or started a new OP medication during follow-up. Long-term sequential treatment strategy trials would inform optimal medication treatment for OP.

Pharmacologic regimens for knee osteoarthritis prevention: can they be cost-effective?

OBJECTIVE: We sought to determine the target populations and drug efficacy, toxicity, cost, and initiation age thresholds under which a pharmacologic regimen for knee osteoarthritis (OA) prevention could be cost-effective. DESIGN: We used the Osteoarthritis Policy (OAPol) Model, a validated state-transition simulation model of knee OA, to evaluate the cost-effectiveness of using disease-modifying OA drugs (DMOADs) as prophylaxis for the disease. We assessed four cohorts at varying risk for developing OA: (1) no risk factors, (2) obese, (3) history of knee injury, and (4) high-risk (obese with history of knee injury). The base case DMOAD was initiated at age 50 with 40% efficacy in the first year, 5% failure per subsequent year, 0.22% major toxicity, and annual cost of $1,000. Outcomes included costs, quality-adjusted life expectancy (QALE), and incremental cost-effectiveness ratios (ICERs). Key parameters were varied in sensitivity analyses. RESULTS: For the high-risk cohort, base case prophylaxis increased quality-adjusted life-years (QALYs) by 0.04 and lifetime costs by $4,600, and produced an ICER of $118,000 per QALY gained. ICERs >$150,000/QALY were observed when comparing the base case DMOAD to the standard of care in the knee injury only cohort; for the obese only and no risk factors cohorts, the base case DMOAD was less cost-effective than the standard of care. Regimens priced at $3,000 per year and higher demonstrated ICERs above cost-effectiveness thresholds consistent with current US standards. CONCLUSIONS: The cost-effectiveness of DMOADs for OA prevention for persons at high risk for incident OA may be comparable to other accepted preventive therapies.

Resource utilization in cancer patients with bisphosphonate-associated osteonecrosis of the jaw.

BACKGROUND AND OBJECTIVE: Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is an emerging oral complication that occurs most commonly in the setting of high-dose bisphosphonate therapy for cancer. The purpose of this study was to estimate the health care-related costs associated with a diagnosis of BONJ in patients with cancer evaluated and managed at one tertiary oral medicine practice. METHODS: This was a retrospective electronic medical record review of cancer patients with BONJ. All health care-related resources were abstracted using a structured chart abstraction tool; data captured included medications, imaging studies, laboratory investigations, procedures, and visits. Standardized references were used to assign costs in 2010 US dollars. RESULTS: Ninety-two cancer patients with BONJ were identified who were followed for a median of 12 months. The median cost of a case of BONJ was $1667 (interquartile range from $976 to $3350). Medication costs comprised the majority (42%) of the total costs, followed by procedural interventions (22%), clinic visits (19.5%), and imaging studies (13.8%). Patient factors associated with higher median costs included a greater number of involved oral quadrants and more advanced BONJ stage. CONCLUSION: There are considerable costs associated with the diagnosis and management of BONJ in patients with cancer, with medications accounting for nearly half of resource expenditures.

Ninety-one osteoporosis patients affected with bisphosphonate-related osteonecrosis of the jaw: a case series.

Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) presents with necrotic bone in the mouth in the setting of BP exposure. It has been studied in cancer patients taking high-dose BP, but BRONJ has also been noted in patients taking lower-dose BP for osteoporosis. The purpose of this study was to characterize the phenotypes and outcomes in a large series of patients with osteoporosis and BRONJ in the setting of BP exposure. We conducted a retrospective case series. The sample was composed of subjects with BRONJ and osteoporosis. Subjects with a history of BP treatment for myeloma or metastatic cancer to the bones were excluded. Descriptive statistics were computed for the study variables. Ninety-one cases of BRONJ met the inclusion criteria. Subjects had a median age of 71 years and were predominantly female (94.5 %). The median time of BP exposure was 60 months (range 2-120). Most subjects were treated with alendronate (82.4 %). The mandible was involved more frequently (58.2 %) than the maxilla (37.3 %). Subjects commonly (65.9 %), but not universally, reported pain. For subjects with treatment outcome data (n = 0), most reported improvement (80.0 %). Although BRONJ is an uncommon condition, the absolute number of cases is fairly large due to the very large number of patients taking BPs for osteoporosis. The findings of this study confirm that BRONJ primarily affects the mandible, a substantial minority present without pain, and patients typically improve with treatment.

Disease-modifying drugs for knee osteoarthritis: can they be cost-effective?

OBJECTIVE: Disease-modifying osteoarthritis drugs (DMOADs) are under development. Our goal was to determine efficacy, toxicity, and cost thresholds under which DMOADs would be a cost-effective knee OA treatment. DESIGN: We used the Osteoarthritis Policy Model, a validated computer simulation of knee OA, to compare guideline-concordant care to strategies that insert DMOADs into the care sequence. The guideline-concordant care sequence included conservative pain management, corticosteroid injections, total knee replacement (TKR), and revision TKR. Base case DMOAD characteristics included: 50% chance of suspending progression in the first year (resumption rate of 10% thereafter) and 30% pain relief among those with suspended progression; 0.5%/year risk of major toxicity; and costs of $1,000/year. In sensitivity analyses, we varied suspended progression (20-100%), pain relief (10-100%), major toxicity (0.1-2%), and cost ($1,000-$7,000). Outcomes included costs, quality-adjusted life expectancy, incremental cost-effectiveness ratios (ICERs), and TKR utilization. RESULTS: Base case DMOADs added 4.00 quality-adjusted life years (QALYs) and $230,000 per 100 persons, with an ICER of $57,500/QALY. DMOADs reduced need for TKR by 15%. Cost-effectiveness was most sensitive to likelihoods of suspended progression and pain relief. DMOADs costing $3,000/year achieved ICERs below $100,000/QALY if the likelihoods of suspended progression and pain relief were 20% and 70%. At a cost of $5,000, these ICERs were attained if the likelihoods of suspended progression and pain relief were both 60%. CONCLUSIONS: Cost, suspended progression, and pain relief are key drivers of value for DMOADs. Plausible combinations of these factors could reduce need for TKR and satisfy commonly cited cost-effectiveness criteria.

Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges.

UNLABELLED: Bisphosphonate-related osteonecrosis of the jaw (BONJ) is an adverse effect of bisphosphonate use with a poorly described epidemiology in osteoporosis patients. We examined the literature and two new cohorts for BONJ. The literature suggests an incidence rate of 0.028 % to 4.3 %. Our cohort studies found an incidence of 0.02 % (95 % CI 0.004 %-0.11 %). INTRODUCTION: We examined the epidemiology of BONJ associated with osteoporosis dosing of bisphosphonates. METHODS: First, we systematically searched the literature about osteoporosis BONJ. Identified studies were abstracted by two authors. Second, we attempted to estimate the relative risk of BONJ among bisphosphonate users with osteoporosis. Two different large insurance databases, one from 2005-2007 and another from 2007-2010, combined with medical record review, were searched. The older dataset did not include the International Classification of Diagnoses (ICD) diagnosis code for osteonecrosis of the jaw (ONJ; ICD 733.45). Incidence rates and relative risks were estimated using Cox regression. RESULTS: The literature review produced nine studies of varying quality. The incidence rates for BONJ among osteoporosis patients varied from 0.028 % to 4.3 %. Two prior studies estimated the relative risk of ONJ related to bisphosphonates and found odds ratios of 7.2 and 9.2. Our attempts to estimate the incidence rate of BONJ encompassed 41,957 in the dataset from 2005-2007 and 466,645 in a separate dataset from 2007-2010. From the older dataset, we found 51 potential cases of BONJ using a broad definition of possible ONJ. One case was confirmed by a dentist for a prevalence of 0.02 % (95 % CI 0.004 %-0.11 %) among bisphosphonate users. From the newer dataset, we found 13 possible cases, but none could be confirmed. Most subjects with the ONJ diagnosis code appeared to have had an osteoporosis-related fracture and not ONJ. CONCLUSIONS: The literature suggests a broad range of possible values for the prevalence of BONJ; our estimate fell within the range from prior literature.