Citations

Objective To investigate the effect of therapies on radiographic progression in patients with axial spondyloarthritis (SpA). Methods A comprehensive database search for studies assessing radiographic progression in axial SpA (particular treatment versus no treatment of interest) was performed. Study‐specific standardized mean differences in treatment outcomes at 2 and ≥4 years were estimated and combined using random‐effects models. Results Twenty‐four studies in patients with axial SpA were identified, of which 18 involved tumor necrosis factor inhibitors ( TNF i), 8 involved nonsteroidal antiinflammatory drugs ( NSAID s), and 1 involved secukinumab. Spinal radiographic progression, as measured by the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ), was not significantly different between TNF i‐treated and biologics‐naive patients at 2 years ( mSASSS difference −0.73 [95% confidence interval (95% CI ) −1.52, 0.12], I 2 = 28%) and ≥4 years ( mSASSS difference −2.03 [95% CI −4.63, 0.72], I 2 = 63%). Sensitivity analyses restricted to studies with a low risk of bias showed a significant difference in spinal radiographic progression between TNF i‐treated and biologics‐naive patients at ≥4 years ( mSASSS difference −2.17 [95% CI −4.19, −0.15]). No significant difference in spinal radiographic progression was observed between NSAID ‐treated and control patients ( mSASSS difference −0.30 [95% CI −2.62, 1.31], I 2 = 71%) or between secukinumab‐treated and biologics‐naive patients ( mSASSS difference −0.34 [95% CI −0.85, 0.17]). With regard to treatment differences in patients with nonradiographic axial SpA or in patients with radiographic progression measured using the sacroiliac joint score, an insufficient number of studies were available for analysis. Conclusion Although no significant protective effect of TNF i treatment on spinal radiographic progression was seen over the course of 2 years or ≥4 years in patients with axial SpA, our analysis restricted to studies with a low risk of bias showed a protective effect of TNF i after ≥4 years. Therefore, long‐term TNF i exposure might confer beneficial effects on spinal radiographic progression in axial SpA. No difference in radiographic progression at 2 years was seen in either the NSAID or secukinumab treatment groups compared to their controls. Future studies should explore the effects of biologic treatment on radiographic progression, as well as the effects of long‐term biologics exposure, in patients with early axial SpA or those with nonradiographic axial SpA.

Objective Since comorbidities such as autoimmune diseases may be associated with rheumatoid arthritis (RA) risk, we hypothesized that a family history of these other conditions might also predict RA. Therefore, we aimed to determine the association between family history of 79 comorbidities and RA. Methods This case–control study identified 821 cases of RA in the Mayo Clinic Biobank (positive predictive value 95%) and matched 3 controls to each case based on age, sex, recruitment year, and location. Patients self reported family history and characteristics (adjusted). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for RA risk according to the presence of family history for each comorbidity, adjusted for body mass index, race, and smoking. Results Family history of several conditions was associated with developing RA, including rheumatic autoimmune diseases (OR adj 1.89 [95% CI 1.41–2.52]), pulmonary fibrosis (OR adj 2.12 [95% CI 1.16–3.80]), inflammatory bowel disease (OR adj 1.45 [95% CI 1.05–1.98]), hyper/hypothyroidism (OR adj 1.34 [95% CI 1.10–1.63]), and obstructive sleep apnea (OR adj 1.28 [95% CI 1.05–1.55]). Parkinson’s disease and type 2 diabetes mellitus were associated with a statistically decreased risk of RA that did not reach the prespecified significance threshold of P < 0.01 (OR adj 0.70 [95% CI 0.49–0.98] and OR adj 0.81 [95% CI 0.67–0.97], respectively). Analyses among 143 cases of incident RA were similar and also suggested an association with a family history of autism (OR 10.5 [95% CI 2.51–71.3]). Conclusion Family history of several autoimmune and nonautoimmune comorbidities was associated with increased risk of RA, providing an opportunity to identify novel populations at risk for RA.

ObjectiveThe objective of this study is to compare biologic drug discontinuation rates for older‐ versus younger‐onset rheumatoid arthritis (YORA) because this is a key outcome measure that could impact prescribing practices.MethodsWe performed a retrospective medical record review of all patients who fulfilled the 1987 American College of Rheumatology (ACR) criteria for adult‐onset rheumatoid arthritis (RA) in 1999‐2013 among residents of a geographically defined area, with follow‐up until death, migration, or July 1, 2017. Discontinuation rates were estimated using cumulative incidence adjusted for the competing risk of death.ResultsA total of 240 cases of elderly‐onset rheumatoid arthritis (EORA) and 366 cases of YORA were identified (65% and 73% female, respectively; P = 0.025). Cumulative incidence of biologic initiation was lower among the EORA cohort compared with the YORA cohort (18% vs 33%, respectively, at 10 years after RA incidence; P < 0.001). Among those treated with a biologic, years from RA diagnosis to first biologic treatment was not significantly different between the two groups (P = 0.62). Drug survival of first biologic was 64% at 1 year (95% confidence interval [CI]: 45%‐77%) and 53% at 2 years (95% CI: 33%‐66%) for EORA, compared with 61% at 1 year (95% CI: 50%‐69%) and 45% at 2 years (95% CI: 34%‐53%) for YORA (P = 0.75). Concurrent glucocorticoid use at initiation of first biologic was statistically and significantly associated with a lower risk of discontinuation in EORA (hazard ratio 0.21; 95% CI: 0.08‐0.53) but not in YORA (interaction P = 0.04).ConclusionDrug survival rates of biologic medications did not differ significantly between patients with EORA and YORA.

Abstract Background Ex-vivo analysis of platelet inhibition by aspirin (ASA) suggests that an optimal decrease in platelet function occurs when 90-95% of platelets are inhibited with ASA. In patients with known vascular disease a daily aspirin decreases the probability of a future vascular event by about 25%. However, platelets from patients with diabetes mellitus (DM) are highly reactive with an increased turnover rate, and prophylaxis with a daily aspirin is not nearly as effective. Because platelet response among individuals is highly variable, we developed a light aggregation based assay that measures platelet function with 100% blockade of an individual’s platelet thromboxane A2 receptor (100% “aspirinated” platelets). This assay is utilized to determine the percentage of platelets inhibited by aspirin, “aspirinated” platelets (ASA-PLTS). Methods Platelet prostaglandin agonist (PPA), (Analytical Control Systems, Fishers IN) an agonist known to be sensitive to the amount of platelet inhibition with aspirin, was used to develop a light aggregometry based technique that measures ASA-PLTS. A specific inhibitor of the thromboxane A2 receptor SQ 29,548(S.Q.)(Cayman Chemicals, Ann Arbor, Mi.) was used to verify that maximal (100%) inhibition of platelets by aspirin was present 2 hrs after ingestion of 325mg ASA. In separate experiments platelets obtained 2 hrs after 325mg ASA (100% ASA-PLTS) were mixed with platelets from the same subject obtained just before aspirin ingestion (0% ASA-PLTS) so that the PPA light aggregation slopes could be measured with 95%, 90%, 85% and 80% ASA-PLTS. The slope of the PPA-AGG curve measured 24 hours after 325mg ASA was compared to the slopes obtained with known concentrations of ASA-PLTS using the formula T24-T2/ T0-T2. (T24= slope 24 hrs post ASA; T2=slope 2 hrs post ASA; T0=slope off ASA). Results Two hours after ingestion of 325mg ASA the slopes of the PPA-AGG curves with and without S.Q. were identical in 7 normal subjects reflecting the aspirin response with 100% ASA-PLTS. Because of the large range of response among individuals, eac subject served as their own control to develop an aspirin response curve for the different percentages of ASA-PLTS. 24 hours after 325mg ASA the percentage of ASA-PLTS in 6 of 7 normal subjects was greater than 90%. Conclusion 1. The slope of the PPA stimulated light aggregation curve with and without S.Q. obtained 2 hrs after 325mg of aspirin in normal subjects can be used as a measure of 100% ASA-PLTS response. 2. Platelet response in most normal subjects 24 hours after aspirin shows that at least 90% of their platelets are “aspirinated”. Comment This technique can identify patients, like those with DM whose percentage of ASA-PLTS may fall below 90% at the end of the dosing interval. A shorter aspirin dosing interval in these patients may result in a higher percentage of ASA-PLTS at the end of the dosing period and possibly decrease the patient’s probability of a subsequent vascular event, but these questions can only be answered with clinical studies. Disclosures: No relevant conflicts of interest to declare.

5078 Background: Strategies integrating androgen targeted and locoregional therapies are being increasingly used in PCa with regional spread, but are rarely curative. Angiogenesis inhibitors delay progression in castration resistant PCa and may synergize with ADT through endothelial cell apoptosis in hormone naïve patients (pts). We hypothesized that the frontline combination of ADT with the potent VEGF inhibitor Axi would improve PCa control relative to ADT alone and allow for meaningful time off systemic therapy after surgical consolidation. Methods: Pts with either clinically detected LN+ (TxN1M0 or TxNxM1a) or very high risk for LN PCa were treated with ADT for 2 mos and then randomized 2:1 to respectively add open label Axi (5 mg PO bid) vs. continue ADT alone for 4 mos until surgery. Those responding with PSA ≤5 ng/mL were offered prostatectomy and extended pelvic lymphadenectomy (RP). ADT +/- Axi was withheld postoperatively and PSA measured q3 mos until 1 y. Primary objective: proportion of pts progression free (FFP) 12 mos after RP, defined as PSA ≤1.0 ng/mL and no radiation or ADT, aiming to detect a 35% difference favoring ADT+Axi. Results: 72 pts completed accrual. We report on the 54 pts with LN+ disease: median age 62 y (range 42-76), pretreatment PSA 22.9 ng/mL (range 3.6 - 404.4), 38 N1 / 16 M1a. Table shows presurgical therapy outcomes. Path responses in the prostate were similar between arms, but in 5 ADT+Axi vs. 0 ADT LN+ pts there was no residual nodal disease. Testosterone recovery: 24/26 ADT+Axi and 9/9 ADT RP pts by 6 mos. 21/36 ADT+Axi and 15/18 ADT pts have failed; 1 y FFP estimates 48.0% (SE 8.6%) and 16.7% (SE 8.3%), respectively (p = 0.02). 1 y undetectable PSA 9 pts (6 ADT+Axi). No grade 4 toxicities or unexpected side-effects were observed. Conclusions: 1 year after RP, ADT+Axi resulted in proportionally greater number of LN+ PCa pts off treatment and progression free than ADT alone. Tissue analysis is evaluating predictors of benefit to further develop angiogenesis inhibition as part of combination strategies for hormone naïve PCa. Clinical trial information: NCT01409200. [Table: see text]

ObjectiveRheumatoid arthritis (RA) is postulated to originate at mucosal surfaces, particularly the airway mucosa. To investigate this hypothesis, we determined the association between RA and asthma, passive smoke exposure, and age at start of smoking.MethodsFor this case–control study, we identified 1,023 cases of RA (175 incident) within a single‐center biobank population, using a rules‐based algorithm that combined self‐report with 2 diagnostic codes. Exposures were self‐reported on biobank questionnaires. Logistic regression models were used to calculate the association of exposures with RA, adjusting for potential confounders. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.ResultsAfter adjustment for allergies, urban environment, and passive smoke exposure, asthma was found to be associated with RA in the full cohort (OR 1.28 [95% CI 1.04–1.58; P = 0.02]) but not the incident RA cohort (OR 1.17 [95% CI 0.66–2.06; P = 0.60]). History of allergic disease was associated with RA in both the full cohort (OR 1.30 [95% CI 1.12–1.51; P < 0.001]) and the incident RA cohort (OR 1.61 [95% CI 1.11–2.33; P = 0.01]), especially food allergy, which was significantly associated with RA in the full cohort (OR 1.38 [95% CI 1.08–1.75; P = 0.01]) and showed a trend toward significance in the incident RA cohort (OR 1.83 [95% CI 0.97–3.45; P = 0.06]). Passive smoke exposure at home or work was not associated with RA. Finally, age at start of smoking was not associated with increased odds of developing RA in either the full cohort (OR 1.03 [95% CI 1.00–1.06; P = 0.03]) or the incident RA cohort (OR 1.00 [95% CI 0.92–1.08; P = 0.98]).ConclusionAsthma and allergies may be associated with increased risk of RA. Passive smoke exposure and early age at start of smoking do not appear to influence risk of RA.

PurposeSize‐specific dose estimates (SSDE) conversion factors have been determined byAAPMReport 204 to adjustCTDIvolto account for patient size but were limited to bodyCTexaminations. The purpose of this work was to determine conversion factors that could be used for anSSDEfor helical, headCTexaminations for patients of different sizes.MethodsValidated Monte Carlo (MC) simulation methods were used to estimate dose to the center of the scan volume from a routine, helical head examination for a group of patient models representing a range of ages and sizes. Ten GSF/ICRP voxelized phantom models and five pediatric voxelized patient models created from CT image data were used in this study. CT scans were simulated using a Siemens multidetector row CT equivalent source model. Scan parameters were taken from the AAPM Routine Head protocols for a fixed tube current (FTC), helical protocol, and scan lengths were adapted to the anatomy of each patient model. MC simulations were performed using mesh tallies to produce voxelized dose distributions for the entire scan volume of each model. Three tally regions were investigated: (1) a small 0.6 cc volume at the center of the scan volume, (2) 0.8–1.0 cm axial slab at the center of the scan volume, and (3) the entire scan volume. Mean dose to brain parenchyma for all three regions was calculated. Mean bone dose and a mass‐weighted average dose, consisting of brain parenchyma and bone, were also calculated for the slab in the central plane and the entire scan volume. All dose measures were then normalized by CTDIvolfor the 16 cm phantom (CTDIvol,16). Conversion factors were determined by calculating the relationship between normalized doses and water equivalent diameter (Dw).ResultsCTDIvol,16‐normalized mean brain parenchyma dose values within the 0.6 cc volume, 0.8–1.0 cm central axial slab, and the entire scan volume, when parameterized byDw, had an exponential relationship with a coefficient of determination (R2) of 0.86, 0.84, and 0.88, respectively. There was no statistically significant difference between the conversion factors resulting from these three different tally regions. Exponential relationships between CTDIvol,16‐normalized mean bone doses hadR2values of 0.83 and 0.87 for the central slab and for the entire scan volume, respectively. CTDIvol,16‐normalized mass‐weighted average doses hadR2values of 0.39 and 0.51 for the central slab and for the entire scan volume, respectively.ConclusionsConversion factors that describe the exponential relationship between CTDIvol,16‐normalized mean brain dose and a size metric (Dw) for helical head CT examinations have been reported for two different interpretations of the center of the scan volume. These dose descriptors have been extended to describe the dose to bone in the center of the scan volume as well as a mass‐weighted average dose to brain and bone. These may be used, when combined with other efforts, to develop an SSDE dose coefficients for routine, helical head CT examinations.

ObjectiveTo identify longitudinal predictors of discordance between patients with rheumatoid arthritis (RA) and their health care providers, where patient global assessment of disease activity is substantially higher than provider global assessment.MethodsThis retrospective case–control study included 102 cases with positive discordance (i.e., ≥25 mm between patient and provider global assessments) and 102 controls without discordance who were matched for age, sex, RA duration, and Clinical Disease Activity Index (CDAI) score. Data were collected at the baseline visit (date of diagnosis or earliest available visit), the index visit (participation in a previous cross‐sectional study), and at up to 11 additional visits before the index visit. Data included patient characteristics, disease activity measures, Disease Activity Score in 28 joints (3‐variable) using the C‐reactive protein level (DAS28‐CRP), and medications. Data were analyzed by using linear and logistic regression models with smoothing splines for nonlinear trends.ResultsOverall, the mean age was 63 years, 75% of patients were female, and the mean RA duration was 10 years. Compared with controls, cases had higher rates of discordant visits during the 4 years before the index visit, and they had a higher CDAI score and DAS28‐CRP earlier in the disease course. Cases more frequently had antinuclear antibodies, nonerosive disease, prior depression, or prior use of antidepressants or fibromyalgia medications. Disease‐modifying medication use was not different between cases and controls.ConclusionThe findings inform new hypotheses about the relationships of disease activity and antinuclear antibodies to the later occurrence of positive discordance among patients with RA.