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733 Background: VHL disease is a rare hereditary condition that causes abnormal tumor growth in multiple organs, including renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas (Hb), pancreatic neuroendocrine tumors (pNET), and other tumors. Repeated surgeries are often required due to ongoing tumor recurrences and can lead to complications such as chronic kidney disease, pancreatic insufficiency, and neurological deficit. Belzutifan is a hypoxia-inducible factor inhibitor approved in the US for the treatment of VHL-associated RCC, CNS Hb, or pNET not requiring immediate surgery. This study aimed to quantify the annual rate and costs of VHL-related surgeries and surgical complications before and after belzutifan initiation. Methods: Surgeries were observed during the periods before and after belzutifan initiation in the single-arm phase 2 LITESPARK-004 trial (NCT03401788) among adults with VHL-RCC. Rates of RCC surgeries were obtained by fitting exponential survival models to: time from treatment initiation to the next renal surgery; and time (looking backward) from treatment initiation to the most recent renal surgery before treatment. Rates of surgeries related to other VHL manifestations were calculated as number of surgeries divided by person-years at risk, using all available post-treatment follow up (151 person-years; median [range] per patient: 29.2 [4.2-37.5] months) and equivalent person-years in the pre-treatment period. Complication risks per surgery and unit costs of surgeries and complications were obtained from a retrospective study on VHL within the Optum Clinformatics Data Mart (2000-2020). Annual per-patient costs of surgeries and complications were estimated in 2020 US dollars over the pre- and post-treatment periods from a US third-party payer perspective. Results: Among trial participants (N=61), the rate of RCC surgeries (surgeries/person-year) decreased 87% (0.108 to 0.014) after belzutifan initiation. The rate of other surgeries decreased 98% (0.265 to 0.007), with CNS Hb surgeries decreasing from 0.185 to 0.007, pNET surgeries from 0.013 to 0, adrenal lesion surgeries from 0.007 to 0, and retinal Hb surgeries from 0.060 to 0. Belzutifan was accordingly estimated to reduce per-patient average annual costs of surgeries and complications from $57,259 to $2,536. Conclusions: Healthcare costs of surgeries and surgical complications are substantial among patients with VHL-RCC. In a trial-based cost-consequence analysis, belzutifan was estimated to decrease annual surgery and complication costs by 96%, based on observed reductions in VHL-related surgeries. [Table: see text]

Electrochemical discharge machining (ECDM) is an emerging micromachining method to drill advanced non-conductive materials such as Hexagonal boron nitride (hBN). Physical contact of micro tools with work material could cause machining inaccuracies, excessive tool wear, and even tool breakage. In this study, a control system based on monitoring the force generated by the ECDM gas film has been developed to achieve non-contact machining of ECDM by dynamically adjusting the tool feed rate. The accuracy of the control system was verified by accelerometer and Fast Fourier Transformation (FFT) data. In the modules, it was found that a non-contact machining process requires the FFT amplitude to be lower than 42 V for a 1200 rpm tool rotation. The experimental results show consistent micro-holes with an average diameter of 650 µm and less than 20 µm error in the overcut achieved using this control system.

OBJECTIVE. Dual-energy CT (DECT) involves the acquisition of CT attenuation data at two different energy levels. In musculoskeletal imaging, gout detection is the most validated clinical indication for DECT. However, there is emerging evidence for several other clinical musculoskeletal applications, including metal artifact reduction and bone marrow imaging for traumatic, neoplastic, and inflammatory processes. CONCLUSION. In this article, we review the current role of DECT in musculoskeletal imaging, primarily focusing on nongout entities.

4543 Background: Prior research shows that post-nephrectomy recurrence is correlated with significantly increased mortality in patients (pts) with intermediate-high (int-high) risk and high risk RCC. However, no study has quantified the incremental OS associated with increased time to recurrence (ToR). Additionally, limited evidence is presented on the variation of recurrence rate and OS by stage of RCC. Methods: The SEER-Medicare database (2007–2016) was used in this retrospective observational study. Post-nephrectomy pts with newly diagnosed, int-high risk (pT2 N0 high grade, pT3 N0 any grade) or high-risk (pT4 N0 any grade, pT any N1 any grade) RCC were identified and stratified based on tumor stage and grade. Grade was defined based on Furhman grading system and was reported in SEER Registry. Post-nephrectomy recurrence free rates and OS by disease stage were described using Kaplan-Meier analyses. OS from nephrectomy in pts with recurrence vs pts without recurrence was compared by disease stage. Multivariable regression analysis was used to quantify the incremental OS associated with increased ToR post-nephrectomy in all pts with recurrence. Results: 643 pts met the inclusion criteria (269 with vs 374 without recurrence; median follow-up: 23 months). The mean age was 75.5 years (yrs), 61% male, and 86% white. Results presented in the table showed wide variance in 5-yr recurrence-free rate in int-high risk group (28%-63%) and indicated substantial risk of disease recurrence in all subgroups of int-high risk pts. Among those with T3 Grade 1-2, T3 Grade 3, and T3 Grade 4 disease, pts with recurrence had significantly higher risk of death than those without (all ps

4539 Background: VHL disease is an inherited condition associated with tumors in multiple organs; RCC may affect up to 70% of patients with VHL. Patients often need many tumor reduction procedures (TRP) to manage renal neoplasms. This study evaluated TRP treatment patterns, costs, and complications among patients with VHL-RCC. Methods: Using an algorithm based on VHL manifestations, patients with VHL were identified from the Optum Clinformatics claims database. Patients were then selected with a prior RCC diagnosis. Minimum continuous enrollment of 12 months before and 3 months after first observed RCC diagnosis was required. TRPs for RCC included nephrectomy, renal ablation, and cryotherapy. Time to first TRP from initial observed RCC diagnosis was estimated using Kaplan-Meier analysis. Mean hospitalization costs per TRP type were estimated. Costs associated with TRP complications were estimated via linear regression; the explanatory variable was the presence of a given complication. Short-term complications were evaluated for 4 weeks post-TRP; long-term ones were evaluated over 6 months. Renal function was evaluated using chronic kidney disease (CKD) stages before and after TRPs, using diagnosis codes and eGFR lab values. Results: 160 patients with VHL-RCC were identified; mean follow-up time was 34.1 months. 115 (71.8%) patients incurred ≥1 RCC TRP over their study period. 68.4% had a TRP in the first year after RCC diagnosis and 76.5% had TRPs by year 5. Of the 125 observed TRPs, 97 (77.6%) were nephrectomies and 28 (22.4%) were ablation/cryotherapy. The mean costs for nephrectomy were nominally higher vs. ablation/cryotherapy ($29,313 vs. $18,290). The most common short-term complications were respiratory related (20.8%) and vascular injury/anemia (13.6%). The most common long-term complications were CKD stage 1-5 (24.0%) and end-stage renal disease (chronic dialysis dependence) (4.0%). The most expensive complications were related to impaired renal function: acute renal failure ($21,013 over 4 weeks), CKD ($26,032 over 6 months) and end stage renal disease ($65,338 over 6 months). At baseline, the proportion of patients with a diagnosis of CKD ≥ stage 3 was similar between patients who had TRPs (n = 115) and those who did not have TRPs (n = 45): 24.3% and 24.4%, respectively. After the first TRP, the proportion of patients with CKD ≥ stage 3 increased from 24.3% to 41.7%. Conclusions: Patients with VHL-RCC incur a significant clinical and economic burden related to TRPs for managing their renal tumors. This is in addition to the burden that VHL-RCC patients incur from the management of other VHL tumors. This study underscores the need for novel effective therapies to prevent or delay the recurrence of VHL-related renal neoplasms to mitigate the burden of morbidity and long-term medical management related to VHL.

e16526 Background: Real world evidence (RWE) on patient outcomes among early-stage non-metastatic renal cell carcinoma (RCC) patients (pts) of different risk groups are limited. This RWE study evaluated disease free survival (DFS) and overall survival (OS) patterns and risk of OS among pts with non-metastatic RCC in the US. Methods: This retrospective analysis identified pts, age ≥18 years, with non-metastatic RCC diagnosis between 01/01/2012-12/31/2015, and surgical treatment for RCC prior to metastatic diagnosis. Pts were identified from the ConcertAI Oncology Dataset which draws electronic medical records from 100 community oncology clinics in the US and followed until 08/19/2021. Pts were stratified into intermediate (int)-high (pT2N0 high grade, pT3N0) or high risk (pT4N0, pTanyN1) RCC. Time to event outcomes (DFS, OS) were examined using Kaplan-Meier methods, and association of recurrence and 5yr OS was examined using Cox proportional hazard model, controlling for baseline and clinical characteristics. DFS was defined as time from initial nephrectomy to first recurrence or death, whichever occurred first. OS was defined as time from initial nephrectomy to death. Results: The study included 274 pts (87% int-high risk, N = 239; 13% high risk, N = 35). Overall, pts were 63.5 yrs (median age), 66% male, 78% White, and 73% had clear cell RCC. Median follow-up was 49.5 months (mths). 54% int-high and 69% high risk pts had recurrence. As seen in the table, median DFS ranged from 14.6-64.8 mths and 5yr DFS rates ranged from 10-61% across risk groups. Median OS was 83.4 mths for int-high and 78.4 mths for high risk pts; 5yr OS rate was 69% for int-high and 58% for high risk. Compared to patients without recurrence, pts with recurrence had shorter median OS (93.8 vs 69.6 mths) and lower 5yr OS rate (85% vs 57%). In pts with recurrence, 5yr OS rate was similar between int-high and high risk groups (58% and 57%). Pts with recurrence were 2.4 times (HR = 2.4; 95% CI = 1.5, 3.9) more likely to die 5 yrs post initial nephrectomy compared to pts without recurrence. Conclusions: This study confirms findings from our previous research with SEER data that pts with recurrence had an increased risk of death, compared to pts without. The DFS and OS rates observed in this RWE study are supportive of DFS and OS rates observed in the placebo arm of the KEYNOTE-564 trial. Additionally, poor DFS rates were observed within subgroups of int-high risk pts. The study results indicate the high real-world unmet need in post-nephrectomy int-high or high risk localized RCC pts, highlight the need for effective adjuvant treatments, and inform the design of future interventional trials in non-metastatic RCC pts.[Table: see text]

This retrospective observational study aimed to compare healthcare resource utilization and costs of Medicare beneficiaries with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who received ibrutinib versus chemoimmunotherapy (CIT) in first line (1 L).Fee-for-service (FFS) and Medicare Advantage (MA) claims data were used to identify adults with a CLL/SLL diagnosis initiating 1 L ibrutinib single agent or CIT between 4 March 2016 and 30 September 2017 (index date). HRU and costs (Medicare spending) were evaluated during 1 L Oncology Care Model (1 L OCM) episodes (the first six months post-index) and over the observed 1 L duration. Patients' baseline characteristics were balanced using inverse probability of treatment weighting. Mean monthly cost differences (MMCDs) obtained from ordinary least square regressions were used to compare costs between ibrutinib and CIT cohorts.In the Medicare FFS dataset (ibrutinib:In Medicare patients with CLL/SLL, 1 L ibrutinib single agent was associated with total monthly cost savings relative to 1 L CIT, driven by lower monthly medical costs that fully offset higher monthly pharmacy costs.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common adult leukemia, accounting for ≈ 37% of all leukemias in the United States. Limited real-word evidence is available on the outcomes of ibrutinib use among previously untreated patients in the U.S. Veterans Health Administration (VHA) population diagnosed with CLL/SLL.To (a) evaluate time to next treatment (TTNT) among U.S. veterans with CLL/SLL who initiated ibrutinib versus chemoimmunotherapy (CIT) in first line (1L) and 1L ibrutinib versus ibrutinib in later lines (2L+) and (b) compare health care resource utilization (HRU) and costs between the 1L ibrutinib and CIT cohorts.Adults with CLL/SLL and claims for 1L single-agent ibrutinib or CIT (index date = first prescription claim date) were included from Veterans Health Administration Data (April 1, 2013-March 31, 2018). A subset of the CIT 1L cohort with evidence of ibrutinib in 2L/3L was defined as the ibrutinib 2L+ cohort. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate TTNT, and generalized linear models were used to determine all-cause per patient per month (PPPM) HRU and costs during 1L among propensity score-matched (PSM) cohorts.After PSM, 614 patients were included in each of the 1L ibrutinib and 1L CIT cohorts, and 149 were included in each of the 1L ibrutinib and 2L+ ibrutinib cohorts. The 1L ibrutinib cohort had significantly longer TTNT compared with each of the 1L CIT and 2L+ ibrutinib cohorts (These findings demonstrate that among U.S. veterans with CLL/SLL, 1L ibrutinib use was associated with significantly longer TTNT versus that of 1L CIT. Similarly, early treatment with ibrutinib was associated with longer TTNT as compared to ibrutinib use in later lines of therapy. Moreover, 1L ibrutinib was associated with lower HRU and medical costs compared with 1L CIT, completely offsetting the higher pharmacy costs related to 1L ibrutinib treatment.This research was sponsored by Janssen Scientific Affairs. The analyses were performed by STATinMED Research. Huang is an employee of Janssen Scientific Affairs and may own company stock. Sundaram was an employee of Janssen Scientific Affairs at the time this study was conducted. Borra and Janjan are employees of STATinMED Research, a paid consultant to the study sponsor. Wang, Li, and Shrestha were employees of STATinMED Research at the time this study was conducted.

To determine whether ultrasound-guided percutaneous sural nerve needle biopsy yields sufficient tissue for analysis in a patient with suspected vasculitis-related peripheral neuropathy. With real-time ultrasound guidance, a hydrodissection of the sural nerve from the adjacent small saphenous vein was first performed. A 14-gauge biopsy needle was then manipulated under real-time ultrasound guidance to obtain two transverse samples of the sural nerve at the lateral distal calf. The biopsy was technically successful and yielded adequate tissue for routine processing. The specimen showed mild epineurial perivascular chronic inflammation with marked loss of myelinated axons. These histologic findings are not diagnostically definitive for vasculitis-related peripheral neuropathy but were supportive of the diagnosis in combination with the patient’s physical examination, laboratory, and electromyography findings. The patient suffered no immediate complications after the procedure. This ultrasound-guided sural nerve needle biopsy, like many surgical biopsies, did not yield a definitive result in a patient with suspected vasculitis-related peripheral neuropathy; however, the procedure was technically successful. Given that percutaneous needle procedures offer many advantages over surgical procedures, we believe that this procedure warrants further investigation.

Introduction Prior studies have reported that hidradenitis suppurativa (HS) is accompanied by a myriad of physical and mental conditions. However, given the small sample sizes and the limited number of pre-selected comorbidities, these studies do not provide a complete picture of the comorbidity burden of HS in the USA. Moreover, the relationship between HS severity and comorbidity burden has yet to be characterized. Using a large US claims database, we estimated the comorbidity burden associated with HS, stratified by disease severity. Methods A retrospective matched cohort design was used. Patients with HS were classified into two severity cohorts (milder and more severe) using an empirical algorithm based on treatments received. The comorbidity burden was compared between each HS cohort and their matched HS-free cohort, and between patients with milder vs. those with more severe forms of HS. Results Several physical and mental comorbidities were found to be more prevalent in both cohorts of patients with milder and more severe forms of HS than in their matched HS-free cohorts. The comorbidity burden also increased greatly as the disease progressed to more severe forms. Conclusions The results of this study highlight the complexity of the comorbidity burden of HS patients and the need for a multidisciplinary approach to optimize the management of HS and its numerous associated comorbidities. Funding AbbVie, Inc. Electronic supplementary material The online version of this article (10.1007/s13555-018-0264-z) contains supplementary material, which is available to authorized users.

Psoriasis is a risk factor for cardiovascular events.To assess the risk of major cardiovascular events and the effect of cumulative treatment exposure on cardiovascular event risk in patients with psoriasis treated with tumor necrosis factor-α inhibitors (TNFis) versus phototherapy.Adult patients with psoriasis were selected from a large US administrative claims database (from the first quarter of 2000 through the third quarter of 2014) and classified in 2 mutually exclusive cohorts based on whether they were treated with TNFis or phototherapy. Cardiovascular event risk was compared between cohorts using multivariate Cox proportional hazards models. Cumulative exposure was defined based on treatment persistence.A total of 11,410 TNFi and 12,433 phototherapy patients (psoralen plus ultraviolet A light phototherapy, n = 1117; ultraviolet B light phototherapy, n = 11,316) were included in this study. TNFi patients had a lower risk of cardiovascular events compared to phototherapy patients (adjusted hazard ratio 0.77, P .05). The risk reduction associated with 6 months of cumulative exposure was 11.2% larger for patients treated with TNFis compared to phototherapy (P .05).Information on psoriasis severity and mortality was limited/not available.Patients with psoriasis who were treated with TNFis exhibited a lower cardiovascular event risk than patients treated with phototherapy. Cumulative exposure to TNFis was associated with an incremental cardiovascular risk reduction compared to phototherapy.

305 Background: VHL disease is an inherited condition characterized by the formation of benign and malignant tumors in multiple organs, and RCC affects up to 40-70% of patients with VHL disease. However, real-world evidence on HRU and direct healthcare costs related to VHL-RCC is lacking. This study sought to address the gap in the literature by evaluating HRU and healthcare costs associated with the disease. Methods: Patients with VHL disease were identified from the Optum Clinformatics claims data using an algorithm based on combinations of manifestations of the disease. Among the patients identified, those with at least 1 diagnosis of RCC were further selected. The index date was defined as the date of first observed RCC diagnosis in the data, and the study period extends up to 5 years after index date or the end of continuous enrollment, whichever was earlier. A minimum continuous enrollment of 12 months prior to and 3 months after the index date was required. All-cause and RCC-related HRU and healthcare costs were evaluated among eligible patients with VHL-RCC. HRU was expressed as events per person-month and cost was expressed as average monthly cost. HRU and healthcare costs related to other VHL disease-related tumors were also assessed, including central nervous system (CNS) hemangioblastomas (Hb), retinal Hb, and pancreatic neuroendocrine tumors (pNETs). Results: 160 patients with VHL-RCC were included in the analyses. Mean age of the patients was 51.5 years and 89 (56%) were male. During the study period, patients with VHL-RCC incurred 0.10 hospitalizations (0.52 inpatient days), 1.49 outpatient visits, 0.09 emergency department (ED) visits, and 0.17 other medical visits per person-month on average. This translated to a monthly all-cause healthcare cost of $4,276, which included $2,222 inpatient, $1,318 outpatient, $188 ED, $63 other medical visits, and $485 pharmacy costs. $1,627 out of the all-cause cost per month was RCC-related, which was mainly driven by inpatient costs for RCC ($1,184/month). There were also notable costs associated with other tumor types: $2,159/month for CNS Hb, $601/month for retinal Hb, and $3,306/month for pNETs on average. Among patients with VHL-RCC who received surgical procedures for different tumors, the average hospitalization or outpatient visit costs were $28,356 for nephrectomies, $70,515 for CNS Hb surgeries, $2,887 for laser therapy of retinal Hb, and $81,825 for pNET surgeries. Conclusions: VHL-RCC is associated with significant HRU and healthcare costs due to the needs of managing RCC as well as tumors in other organs caused by VHL disease. This highlights the multi-disciplinary nature of VHL disease and the need for novel effective therapies to prevent or delay the recurrence of VHL-related tumors in order to mitigate the economic burden related to the disease.

To compare outcomes between adalimumab and etanercept in the treatment of moderate to severe plaque psoriasis.Study groups included patients randomized to adalimumab or placebo (REVEAL and CHAMPION trials) and those randomized to etanercept or placebo (M10-114 and M10-315 trials). Week 12 outcomes were compared between patients receiving adalimumab and those receiving etanercept after adjusting for cross-trial differences in patient characteristics using propensity score weighting and after subtracting effects of placebo. Outcomes included proportion of patients achieving 75% or more, 90% or more, and 100% reductions from baseline in the Psoriasis Area and Severity Index (PASI75, PASI90, PASI100, respectively), symptom resolution (pruritus = 0; psoriatic pain = 0), lesion resolution (minimal scores for plaque signs erythema, desquamation, and induration, and by body regions head, upper limbs, trunk, and lower limbs), absence of skin-related quality-of-life impact (Dermatology Life Quality Index [DLQI] = 0), "complete disease control" (patient's global assessment [PtGA] = 0), and adverse events.After adjustment, baseline characteristics were balanced among study groups (adalimumab = 875 vs. placebo = 427; etanercept = 260 vs. placebo = 130). Compared with etanercept, adalimumab was associated with significantly better placebo-adjusted outcomes (PASI75: 62.3% vs. 42.6%; PASI90: 35.9% vs. 12.1%; PASI100: 13.1% vs. 4.9%; pruritus: 24.7% vs. 13.0%; psoriatic pain: 27.4% vs. 8.7%; DLQI: 27.7% vs. 11.7%; and PtGA: 16.4% vs. 10.6%; all P0.05), except for similar rates of adverse events and head-specific lesion resolution.Compared with etanercept, adalimumab treatment for moderate to severe plaque psoriasis was associated with greater PASI reduction, higher rates of resolution of skin signs and symptoms, and greater improvements in dermatological life quality.

To determine the diagnostic yield of CT-guided percutaneous biopsy of densely sclerotic bone lesions. We retrospectively analyzed CT-guided percutaneous bone biopsies performed at our institution from September 2008 through August 2011 (329 cases) and from September 2012 through August 2015 (324 cases) after adoption of a battery-powered drill system (OnControl). Bone lesions were included in the analysis if they were >70% sclerotic by visual inspection, had a density > 2 times that of adjacent trabecular bone, and had an attenuation of ≥250 HU. Pathological fractures, diskitis–osteomyelitis, and osteoid osteomas were excluded. Eligible cases were characterized by lesion location, maximum lesion diameter, mean density, biopsy needle type and gauge, reported complications, and histological diagnosis. Clinical and imaging follow-up was used to confirm histological diagnosis. Cases in which a benign histological diagnosis could not be confirmed by imaging over a minimum period of 1 year were excluded. A total of 37 biopsies of sclerotic bone lesions met the inclusion criteria, 17 of which were performed with a power drill needle and 20 of which were performed with a manually driven needle. The mean lesion density was 604.1 HU. The overall diagnostic yield was 78.4%; overall diagnostic accuracy was 94.6%, and the false-negative rate was 5.4%. Diagnostic yield and accuracy were 82.4% and 100% respectively, with a power drill and 75% and 90% respectively, with a manual device. Diagnostic yield for lesions ≥700 HU was 90% (9 out of 10). Densely sclerotic bone lesions are amenable to percutaneous needle biopsy.

Osteoid osteoma is a common benign tumor that is typically found in young adults and children, usually in the long bones of the lower extremity. Radiofrequency ablation (RFA) under computed tomography guidance is the standard of care for symptomatic osteoid osteomas. However, patients with osteoid osteoma of the hand or foot are often treated with open surgery because of the risk of injury to vascular and neural structures from RFA. This risk is more pronounced in pediatric patients because of the small lesion size and proximity of lesions to important neurovascular structures. Here, we present 2 pediatric patients, one with an osteoid osteoma in the hand and the other with an osteoid osteoma in the foot. In both patients, a 22-gauge, 2.5-mm active tip ablation probe was used. The smaller ablation volume achieved with this probe protected neighboring neurovascular structures while effectively ablating the osteoid osteoma nidus. Based on our success in these cases, we recommend the application of this method for cases in which neurovascular proximity to the osteoid osteoma lesion makes ablation challenging.

informCLL is the first United States-based registry of patients with chronic lymphocytic leukemia that initiated enrollment after approval of novel targeted agents. Prognostic/predictive testing rates and chronic lymphocytic leukemia treatment selection with availability of novel agents have not been previously investigated in clinical practice. Results from this interim analysis demonstrate that prognostic/predictive testing was infrequently used to guide treatment selection, potentially inhibiting beneficial outcomes for patients. Introduction: The therapeutic landscape for chronic lymphocytic leukemia (CLL) has significantly shifted with the approval of novel agents. Understanding current prognostic testing and treatment practices in this new era is critical. Beginning enrollment in 2015, informCLL is the first United States-based real-world, prospective, observational registry that initiated enrollment after approval of novel agents. Patients and Methods: Eligible patients were age ≥ 18 years, started CLL treatment within 30 days of enrollment, and provided consent. For this planned interim analysis, treatments were classified into 5 groups: ibrutinib, chemoimmunotherapy, chemotherapy, immunotherapy, and other novel agents. Results: Frequency of prognostic testing and treatment patterns are reported among 840 patients (459 previously untreated; 381 relapsed/refractory), enrolled largely (96%) from community practice settings. Testing for chromosomal abnormalities by fluorescence in situ hybridization, TP53 mutation, or IGHV mutation status occurred infrequently among all patients (31%, 11%, and 11%, respectively). Chemoimmunotherapy was the most common treatment in previously untreated patients (42%), whereas ibrutinib was the most common treatment among relapsed/ refractory patients (51%). Of patients who tested positive for del(17p) or TP53 mutation, 34% and 26% received chemoimmunotherapy, respectively. Among patients who did not have fluorescence in situ hybridization or TP53 mutation testing prior to enrollment, 33% and 32% received chemoimmunotherapy, respectively. Conclusion: Our findings indicate that prognostic testing rates were poor, and approximately one-third of high-risk patients (del[17p] and TP53) received chemoimmunotherapy, which is not aligned with current CLL treatment recommendations. This represents an opportunity to educate and alert health care professionals about the necessity of prognostic testing to guide optimal CLL treatment decisions.

4581 Background: Intermediate endpoints (e.g., disease free survival [DFS]) have gained traction lately as potential surrogates for OS in oncology as they require shorter follow up to show clinical benefit. Given the high post-nephrectomy survival in patients (pts) with localized RCC, evidence on if DFS can be used as a predictor of OS in the disease is warranted. We assessed the association between DFS and OS in pts with newly diagnosed, completely resected, intermediate-high (pT2N0 high grade, pT3N0) or high-risk (pT4N0, pTanyN1) RCC post-nephrectomy. Methods: This retrospective observational study used the SEER-Medicare database (2007–2016). DFS was defined as time from initial nephrectomy date to first recurrence (diagnosis of metastatic disease, additional surgery, starting systemic treatment for advanced RCC) or death, whichever occurred first. OS from time of recurrence in pts with recurrence were compared with OS from comparable time point in pts without, using Kaplan-Meier analyses and adjusted Cox models. OS was also compared between pts with and without recurrence by landmark time points at 1, 2, 3, 4 and 5 years (yrs) post-nephrectomy; hazard ratios (HRs) between the two cohorts were estimated using adjusted Cox models. Correlation between DFS and OS was assessed using the Kendall’s τ rank correlation. Monthly healthcare costs were compared between the two cohorts using generalized linear model. Results: 643 post-nephrectomy RCC pts (269 with recurrence vs 374 without) met the inclusion criteria (Median follow-up: 23 months). The mean age was 75.5 yrs, 61% male, and 86% white. The median post-nephrectomy OS and DFS was 8.61 and 4.44 yrs, respectively. Pts with and without recurrence had comparable baseline characteristics. Pts with recurrence had significantly shorter OS than those without [median: 2.53 yrs vs not reached; adjusted HR (95% confidence interval [CI]): 6.00 (4.24–8.48)]. Pts with recurrence by each landmark time point had significantly shorter OS than those without [1 yr post-nephrectomy median OS: 2.35 vs 9.66 yrs, and the OS 1, 3, and 5 after the 1 yr landmark was 69.9 vs 96.5%, 41.8 vs 83.8%, and 37.0 vs 70.1%, respectively; all Ps (log-rank test) < 0.001]. Cox models indicated that pts with recurrence by each landmark time point had 2.6–3.5 times increased risk of death compared with those without. Kendall’s τ rank correlation model demonstrated a statistically significant correlation between DFS and OS (Kendall’s τ = 0.70; 95% CI: 0.65–0.74; P < 0.001). Pts with recurrence had $4,924 and $1,387 higher adjusted all-cause medical costs and pharmacy costs per month (P < 0.001). Conclusions: Post-nephrectomy recurrence is associated with significantly shorter OS among pts with intermediate-high or high-risk RCC, resulting in a strong positive association between DFS and OS in the population. Higher healthcare cost was also seen among pts with recurrence.

Bisphosphonates have been widely used in the treatment of osteoporosis with well-documented long-term efficacy and safety, particularly in postmenopausal patients. But over the past decade, low-energy atypical subtrochanteric and proximal diaphyseal femoral fractures have emerged as an unexpected complication of prolonged bisphosphonate use. To the radiologist unfamiliar with this entity, the findings may be subtle and often missed, potentially evolving from an early incomplete fracture to a displaced complete fracture with a delay in diagnosis. In such instances where the radiographic findings are negative or equivocal and patients present with prodromal symptoms of aching or dull groin or thigh pain, additional work-up with advanced imaging techniques, such as magnetic resonance imaging, computed tomography, or bone scintigraphy, may prove diagnostic owing to their multiplanar capabilities and earlier detection of subtle periosteal changes. It is imperative that radiologists develop a search pattern to help identify such fractures and consider imaging evaluation of the contralateral extremity in suspected cases with prodromal symptoms to assess for an incomplete asymptomatic or minimally symptomatic fracture.

Objective Hidradenitis suppurativa (HS) is often treated by surgery. The risk of recurrence after surgery is common and the consequences are substantial, but neither has been quantified using a claims database. This study aimed to estimate the burden associated with non-curative surgery in HS patients. Methods A retrospective analysis was performed of health insurance claims data from Q1 1999 to Q2 2011 in a US claims database. The analysis included 2668 adults with ≥1 diagnosis of HS and ≥1 claim for skin surgery within 6 months after diagnosis. Healthcare resource utilization and medical costs were compared using multivariate regressions. Results Overall, 46% of HS patients had ≥1 indicator of non-curative surgery. The incidences of inpatient, emergency department, and outpatient visits were 88%, 40%, and 30% higher, respectively, for patients with non-curative surgery vs patients without indicator of non-curative surgery (all p

To describe the radiological features of pes anserine bursitis with intramedullary extension and cortical scalloping and to determine the prevalence of these bony changes among patients with pes anserine bursitis. Reports of knee magnetic resonance imaging (MRI) examinations performed at our institution between July 2007 and June 2017 in patients with pes anserine bursitis were retrospectively reviewed, and a total of 542 cases showing MR evidence of pes anserine bursitis were identified. From these, cases of pes anserine bursitis with intramedullary extension and cortical scalloping were identified. Two experienced musculoskeletal radiologists evaluated the MRI by consensus. The medical records of these patients were also reviewed. Eight patients were diagnosed with pes anserine bursitis with bony changes (prevalence, 1.47% [8 out of 542]), over the study period. All of these patients had a history of chronic knee pain. Seven patients also underwent radiography at the time of diagnosis; these images demonstrated variable appearances depending on the depth of the cortical scalloping and intramedullary extension. On MRI, all patients demonstrated a mass-like fluid extension around the pes anserine bursa and into the bone. None of the patients underwent biopsy; diagnosis was based on MRI features alone. Pes anserine bursitis with intramedullary extension is an unusual presentation of bursitis that may simulate a neoplasm clinically and radiologically. To avoid misdiagnosis, radiologists should be aware of the occurrence of osseous changes in the tibia confluent with pes anserine bursitis.

Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa.PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1:1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12.We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences.Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. (Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively.).

A 32-year-old woman presented with progressive enlargement of the distal phalanx of her great left toe and associated mild to moderate pain.

Previous studies suggest that efficacy is more important than side-effect risks to psoriasis patients. However, those studies did not consider potentially fatal risks of biologic treatments.To quantify the risks patients are willing to accept for improvements in psoriasis symptoms.Adults with a self-reported physician diagnosis of psoriasis were recruited through the National Psoriasis Foundation. Using a discrete-choice experiment, patients completed a series of nine choice questions, each including a pair of hypothetical treatments. Treatments were defined by severity of plaques, body surface area (BSA), and 10-year risks of tuberculosis, serious infection and lymphoma.For complete clearance of 25% BSA with mild plaques, respondents (n = 1608) were willing to accept a 20% (95% confidence interval: 9-26%) risk of serious infection, 10% (5-15%) risk of tuberculosis and 2% (1-3%) risk of lymphoma. For complete clearance of 25% BSA with severe plaques, respondents were willing to accept a 54% (48-62%) risk of serious infection, 36% (28-49%) risk of tuberculosis and 8% (7-9%) risk of lymphoma.Respondents were asked to evaluate hypothetical scenarios. Actual treatment choices may differ.Respondents were willing to accept risks above likely clinical exposures for improvements in psoriasis symptoms. Individual risk tolerances may vary.

Psoriasis (Ps) is a chronic inflammatory immune-mediated skin disease that has been identified as a risk factor for various conditions including neoplasms.To compare prevalence of cancer between Ps and Ps-free patients.Adult patients continuously enrolled for ≥12 months (≥1 month in 2014) were selected from a large United States (US) claims database (Q1:2010-Q4:2014) and classified as Ps patients (≥2 Ps diagnoses; International Classification of Diseases 9th Revision, [ICD-9] code: 696.1x) and Ps-free patients (no Ps diagnosis). Patients were exactly matched (1:1) based on age, gender, state of residence, and insurance plan type. Prevalence of cancer was compared between cohorts over patients' last 12 months of continuous healthcare plan enrollment using logistic-regression models.A total of 179,066 pairs of Ps and Ps-free patients were selected. Median age was 54.0 years, 51.7% were females. Prevalence of cancer was higher among Ps patients for any type of neoplasms (OR [95% confidence interval (CI)]=1.86 [1.83; 1.89]), malignant neoplasms (OR [95% CI]=1.53 [1.49;1.57]), as well as malignant skin neoplasms (OR [95% CI]=1.87 [1.79; 1.95]), lymphatic and hematopoietic tissues (OR [95% CI]=1.70 [1.57;1.84]), genital (OR [95% CI]=1.33 [1.26;1.41]), breast (OR [95% CI]=1.32 [1.24;1.40]), digestive organs and peritoneum (OR [95% CI]=1.24 [1.13;1.35]), urinary organs (OR [95% CI]=1.49 [1.36;1.64]), respiratory and intrathoracic organs (OR [95% CI]=1.30 [1.17;1.44]), and metastatic cancer (OR [95% CI]=1.14 [1.06;1.24]), all P less than 0.01.Impact of Ps severity could not be assessed.Ps patients had a higher prevalence of cancer than Ps-free patients. J Drugs Dermatol. 2018;17(2):180-186.

Background: The clinical benefits of biologic therapies for moderate-to-severe psoriasis are well established, but wide variations exist in patient response. Objectives: To determine the number needed to treat (NNT) to achieve a 75% and 90% reduction in the Psoriasis Area and Severity Index (PASI-75/90) with FDA-approved agents and evaluate the incremental cost per PASI-75 or PASI-90 responder. Methods: The relative probabilities of achieving PASI-75 and PASI-90, as well as NNTs, were estimated using a network meta-analysis. Costs (2017 USD) included drug acquisition and administration. The incremental cost per PASI-75 or PASI-90 responder for each treatment was estimated for the clinical trial period, and annually. Results: Compared with supportive care, the NNT to achieve PASI-75 was 1.18 for ixekizumab, 1.29 for secukinumab 300 mg, 1.37 for infliximab, 1.48 for adalimumab, 1.53 for secukinumab 150 mg, 1.58 for ustekinumab, 2.25 for etanercept, and 3.71 for apremilast. The one-year incremental cost per PASI-75 responder relative to supportive care was $59,830 for infliximab, $88,775 for secukinumab 300 mg, $91,837 for adalimumab, $95,898 for ixekizumab, $97,363 for ustekinumab, $105,131 for secukinumab 150 mg, $129,665 for apremilast, and $159,328 for etanercept. Results were similar for PASI-90. Conclusion: The NNT and incremental cost per responder are meaningful ways to assess comparative effectiveness and cost effectiveness among psoriasis treatments.

Two patient-reported outcome (PRO) questionnaires, the Hidradenitis Suppurativa Symptom Assessment (HSSA) and Hidradenitis Suppurativa Impact Assessment (HSIA), were developed to measure signs, symptoms and impacts of HS in treatment efficacy studies.In accordance with FDA guidelines and published best practices, four stages of research were conducted to create the questionnaires: concept elicitation, questionnaire construction, content evaluation and psychometric evaluation.Subjects (N = 20) who participated in the concept elicitation stage reported 15 unique HS-related signs and symptoms and 51 impacts. Following this, eight sign and symptom concepts and 21 impacts were selected for construction of the HSSA and HSIA, respectively. During content evaluation, cognitive debriefing interviews with HS subjects (N = 20) confirmed subjects could read, comprehend and meaningfully respond to both questionnaires. Modifications made after this stage of work resulted in a nine-item HSSA and a 17-item HSIA. The HSSA and HSIA were subsequently entered into a US-based observational study (N = 40), and the scores produced by each were found to be reliable, construct valid, and able to distinguish among clinically distinct groups.The HSSA and HSIA are content-valid, HS-specific, PRO questionnaires with demonstrated ability to generate reliable, valid scores when administered to patients with HS in a research setting.

Background Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. Objective This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. Methods Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). Results Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [ P .001]) and all ranked secondary end points. The serious adverse event rates (placebo vs adalimumab) in period A were 4.6% versus 7.3%; the serious infections rates were 1.9% versus 3.7%. Limitations Patients with less than 5% BSA involvement were not eligible for enrollment. Conclusions After 26 weeks of adalimumab treatment, significant improvements were seen in the primary and all ranked secondary end points and in signs and symptoms of moderate-to-severe nail psoriasis versus with placebo and no new safety risks were identified.

dear editor, Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic, inflammatory skin disease affecting terminal hair follicles in apocrine-gland-bearing skin.1 Associated comorbidities include depression,2 obesity3 and metabolic syndrome.4 The objective of the current analysis of patients with moderate-to-severe HS was to identify the most common comorbidities, their prevalence according to the level of HS disease burden (high vs. medium) and any association between baseline characteristics and the risk for the comorbidity. These patients, representing one of the largest HS groups to be evaluated to date, were adults from a 52-week, phase 2, randomised, double-blind, placebo-controlled trial of adalimumab treatment,5 who had at least moderate disease [HS Physician's Global Assessment (HS-PGA) grade ≥ 3; 0–5 scale]. Additional inclusion/exclusion criteria were published previously.5 Baseline comorbidities were identified with patient reports and medical histories. The following conditions were defined: hypertension, use of antihypertensive medication and/or self-reported history; uncontrolled hypertension, systolic/diastolic blood pressure (SBP/DBP) ≥ 140/≥ 90 mmHg; depression, Patient Health Questionnaire 9 (PHQ-9) score ≥ 10;6 morbid obesity, body mass index (BMI) ≥ 40 kg m−2; hyperlipidaemia, total cholesterol ≥ 240 mg dL−1; high HS disease burden, HS-PGA > 3 and/or Hurley stage III; and medium HS disease burden, HS-PGA ≤ 3 and Hurley stage II.5 All patients with available baseline values were included in this analysis. All statistical tests were two-sided and significant at 0·05. Associations between the most common comorbidities and baseline characteristics were evaluated by logistic regression. The odds ratio (OR) with 95% Wald confidence interval (CI) was provided. Final models were chosen by stepwise selection with a P-value of 0·15 for both entry and stay. Model selection was conducted per Akaike information criteria and Bayesian information criteria, which confirmed the final models selected by the stepwise selection method. Of the 154 patients in this analysis, 60 (39·0%) had high HS disease burden and 94 (61·0%) had medium burden. Mean high-sensitivity C-reactive protein (CRP) was almost four times higher in the high vs. medium disease burden groups (32·7 mg L−1 vs. 8·7 mg L−1). Combining self-report and medical examination results, 39·6% of patients had hypertension, 38·3% were morbidly obese and 48·1% had depression. The incidence of modifiable cardiovascular risk factors (Table​(Table1)1) revealed that > 50% of patients were smokers, overweight or had hypertension. Other cardiovascular risk factors included hyperlipidaemia (11·7%) and diabetes mellitus (6·5%). Over one-third of patients (35·7%) had two cardiovascular risk factors (Table​(Table11). Table 1 Baseline status of enrolled patients with hidradenitis suppurativa (HS) Of the 40·3% of patients who had and/or were diagnosed with hypertension, or were receiving antihypertensive medication (Fig.​(Fig.1a),1a), 53% had been diagnosed with hypertension, and 31% had been both diagnosed and treated. Of the latter, 53% had reached the treatment goal (SBP/DBP