Weeks Of Corticosteroids Research Articles

Feasibility and Improvement in Survival with a Risk-Adapted Treatment Regimen for Childhood Acute Lymphoblastic Leukemia in a Limited Resource Setting

Introduction: High-intensity therapeutic regimens results in ALL have not been reproduced in limited resource settings, due to the lack of appropriate support therapy, diagnostic methods, limited access to drugs, and high treatment related mortality. For low and middle-income countries, treatment of these patients represents a challenge. In Mexico acute leukemia represents 49% of all pediatric cancers, with a 5-year overall survival between 50 and 60%, a relapse rate of 26%, induction related mortality of 3-10%, and a mortality in remission of 14%. We report the results of an adjusted treatment regimen based on an adapted risk stratification for a limited-resource setting. Objective: To implement a risk stratified treatment protocol for a limited resource setting, with the aim of reducing induction related mortality, and improving EFS and OS. Materials and Methods: From January 2017 to March 2020, all patients diagnosed with ALL between 0 and 15 years of age in a single center in northeast México were captured in a prospectively maintained database. Depending on risk stratification, patients received an adjusted treatment protocol with variations on intensity and duration for the different phases. The main differences were the amount of anthracycline doses during induction (2 for low, 3 for intermediate/high patients), the requirement of at least 20 doses of L-asparaginase for intermediate/high risk patients, and the use of Capizzi-style methotrexate for intermediate risk and high-dose methotrexate only for high-risk patients (Table1). Demographic data was reported using distribution analysis, and the Kaplan-Meier method was used to analyze and predict OS and EFS. Results: There were 59 male and 41 female patients; the median age at diagnosis was 5.5 years. B-cell and T-cell lymphoblastic leukemia was the diagnosis in 94% and 6% patients, respectively, with a follow-up of 41 (0.33-65) months. Regarding risk stratification, 42%, 34%, and 24% children were classified as high, intermediate, and low-risk, respectively. After one week of corticosteroids 80% of patients had a good response, and 84% of patients achieved a negative measurable residual disease (MRD) after induction chemotherapy. Estimated EFS and OS at 5 years were 70% and 77.5% respectively. Of the 93 patients evaluable for response, MRD positivity (16%), induction related mortality (6%), and relapse (16%) rates were lower in this cohort when contrasted with previous protocols. EFS for low, intermediate, and high-risk groups was 73%, 85%, and 56% and OS 88%, 90% and 61% (Figure 1) Conclusions: The implementation of a risk-adjusted chemotherapy regimen adapted for our limited-resource center, improved treatment continuity and was associated with better OS, and EFS. Early relapse rates were also reduced, without increasing induction mortality associated with toxicity. Periodic and prospective outcome evaluation in a limited-resource setting is fundamental to adjust and standardize therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Sweet Syndrome in Early Infancy

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an uncommon inflammatory disease in pediatrics. It presents with fever, blood neutrophilia, and painful erythematous plaques with a dermal neutrophilic infiltrate. In general, it is associated with infections, hematologic and solid tumor, immunodeficiency, and certain drugs. It can easily be mistaken for infection and can lead to prescribe antibiotics or antiviral agents. Here, we describe a case of a 6-week-old infant who developed SS following a pulmonary infection. The patient presented with ocular manifestations and fully recovered after 1 week of corticosteroids.

Treatment Patterns and Bleeding Events Among Patients with Immune Thrombocytopenia Based on Duration of Corticosteroid Treatment

Background: Oral corticosteroids (CS) are often the first line of therapy for immune thrombocytopenia (ITP). Recent guidelines recommend against prolonged CS use (>6 weeks) for adults with ITP and suggest switching to second-line treatments for non-responsive or CS-dependent patients. The duration and potential overuse of CS among newly treated with CS adult ITP patients has yet to be described in a real-world setting. This study quantified the real-world duration of CS use among adult ITP patients newly treated with CS and assessed the clinical and economic consequences of prolonged CS use. Objectives: 1) To describe treatment patterns, bleeding events, and side effects of CS among patients with ITP; 2) To describe healthcare resource utilization (HRU) and costs among patients with ITP treated with CS. Methods: A retrospective observational cohort study was conducted using claims contained in the IBM® MarketScan® Commercial and Medicare Databases. Adult patients with an ITP diagnosis between January 1, 2013 and June 30, 2018 were selected for the study. Patients were required to be newly treated with CS (prednisone, dexamethasone, methylprednisolone) (first CS claim=index date) with at least 12 months of continuous enrollment prior to and 12 months following index. Patients with a diagnosis for any other thrombocytopenia and evidence of causes of secondary thrombocytopenia were excluded. Patients were categorized into cohorts based on CS duration during the follow-up period: CS days' supply ≤6 weeks, >6 weeks to 8 weeks, or >8 weeks. Discontinuation was defined as a gap of >30 days of the index CS following the run-off date of the last observed claim. Bleeding events, incidence of CS side effects (defined as new events occurring during the follow-up period only), HRU and costs (2018 USD), and treatment patterns were described during the follow-up period. Results: Among 1,720 patients who met study inclusion criteria, 65% had ≤6 weeks of CS use, 6% had >6-8 weeks, and 29% had >8 weeks. Median age among all patients was 48 years and majority were female (61%). About three quarters (71%) of patients started on prednisone as the index CS treatment, 16% on methylprednisolone, and 13% on dexamethasone. Patients with higher CS duration of use (>6-8 and >8 week) had a shorter time to CS treatment start following ITP diagnosis (mean 69 and 92 days, respectively; median 5 days for both) compared to the ≤6 week cohort (mean 306, median 152 days). All but one patient discontinued their index CS therapy. Patients with >8 weeks of CS had higher CS restart rates following discontinuation (49%) compared to patients with ≤6 weeks (23%). Among patients who switched therapies following CS discontinuation, those in the ≤6 week cohort had higher utilization of second line ITP agents compared to the >8 week cohort, including eltrombopag (16% vs. 11%) and romiplostim (23% vs. 11%). Patients in the >8 week cohort had higher rates of switching to splenectomy (15%) and rituximab (33%) following CS discontinuation compared to the ≤6 cohort (6% and 26%). About a fifth (19%) of patients experienced a bleeding event during the follow-up period. Bleeding event rates were higher for those with >8 weeks of CS than those with ≤6 weeks (23% vs. 17%). Nearly 40% of all patients experienced a CS side effect and rates were similar among the three cohorts. Patients with greater use of CS (>8 weeks) had higher rates of inpatient admissions (34%) compared to the ≤6 week (22%) and >6-8 week (32%) cohorts. Mean annual all-cause costs were $24,800, $42,706, and $51,896 for the ≤6 week, >6-8 week, and >8 week cohorts, respectively. Conclusions: Patients with ≤6 weeks of CS had the shortest switch time to a non-CS ITP treatment, with higher utilization of thrombopoietin receptor agonists, as compared to patients with greater CS use. Patients with a higher duration of CS use had significantly higher inpatient and outpatient HRU and more than double the healthcare costs compared to patients with ≤6 weeks of CS. The rate of bleeding events was lowest among patients with ≤6 weeks of CS use. Approximately 35% of patients in this study were treated with >6 weeks of CS, indicating a need for earlier intervention with more effective ITP therapies that may reduce CS use and risk of bleeding events, and subsequently decrease the economic burden incurred by patients with prolonged CS exposure. Further study is needed to assess the clinical and economic outcomes related to duration of CS use. Figure Disclosures Hatfield: Amgen Inc.: Current Employment. Manjelievskaia:Amgen Inc.: Consultancy; IBM Watson Health: Current Employment. Evans:Amgen Inc.: Consultancy; IBM Watson Health: Current Employment. Chan:Amgen Inc.: Consultancy; IBM Watson Health: Current Employment. Shah:Amgen Inc.: Current Employment. Saad:Amgen Inc: Current Employment.

CYTOMEGALOVIRUS (CMV) INFECTION CAUSING HEMOPHAGOCYTIC LEUKOHISTIOCYTOSIS (HLH) IN A PATIENT WITH MYASTHENIA GRAVIS

TYPE: Abstract Publication TOPIC: Critical Care PURPOSE: We describe a rare case of CMV-induced HLH in an immunocompromised adult with myasthenia gravis being managed with azathioprine, illustrating the challenge of making the diagnosis of HLH and initiating early treatment. METHODS: A 63-year-old female with medical history significant for myasthenia gravis managed with azathioprine (AZA) presented with fevers, shortness of breath, malaise and night sweats for one week. She was tachycardic, and initial labs were significant for pancytopenia. CT pulmonary embolism and CT abdomen/pelvis studies showed splenomegaly. Further labs suggested CMV infection; she also had hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia, suggestive of HLH, prompting bone marrow biopsy, which was consistent with CMV with early HLH; NK cell activity was undetectable, with high sCD25. She was started on ganciclovir and dexamethasone; once her liver failure and CMV viremia improved, she received etoposide. Fibrinogen, ferritin levels and CMV titers improved but her cytopenias worsened - further etoposide was held. Unfortunately, the patient’s clinical status deteriorated and she passed. RESULTS: HLH is a rare, underdiagnosed disease characterized by hyperinflammation and cytokine dysregulation, leading to severe infections and death. Five of eight HLH-2004 diagnostic criteria are required for acquired HLH, including fever; splenomegaly; cytopenias; hyperferritinemia; hypertriglyceridemia, hypofibrinogenemia; histological evidence of hemophagocytosis; low/absent NK-cell activity, and high levels of sCD25. Treatment involves eight weeks of corticosteroids and etoposide. CONCLUSIONS: CMV-induced HLH is a rare disease and few cases have been reported. Clinicians should consider HLH as a differential diagnosis as early treatment may reduce mortality. CLINICAL IMPLICATIONS: HLH is an underdiagnosed disease associated with high mortality, making a timely diagnosis imperative. DISCLOSURE: No significant relationships. KEYWORDS: hemophagocytic leukohistiocytosis, cytomegalovirus

Vasculitic Peripheral Neuropathy, Differences Between Systemic and Non-Systemic Etiologies: A Case Series and Biopsy Report.

Vasculitic peripheral neuropathy (VPN) is caused by vessel inflammation leading to peripheral nerve injury of acute-to-subacute onset. When VPN occurs in the context of systemic disease it is classified as Systemic Vasculitic Neuropathy (SVN) and as Non-Systemic Vasculitic Neuropathy (NSVN) when restricted to the nerves. This study aimed to compare the clinical characteristics, biopsy findings and disease outcome in patients with VPN. Clinical records of adult patients with VPN diagnosed at our institution between June-2002 and June-2019 were retrospectively reviewed. Demographic characteristics, clinical manifestations, nerve conduction studies, nerve biopsies, treatment and clinical evolution were analyzed in all patients with at least 6 months follow-up. Twenty-five patients with VPN were included (SVN, n = 10; NSVN, n = 15). No significant differences in demographic or clinical features were found between groups. The median delay between symptom onset and nerve biopsy was significantly longer in NSVN patients (10 vs 5.5 months, p = 0.009). Erythrocyte sedimentation rate (ESR) values over 20 mm/h were significantly more common in SVN patients (100% vs. 60%, p = 0.024). Nerve biopsies showed active lesions more frequently in treatment-naive patients compared to those who had received at least 2 weeks of corticosteroids (92% vs 38%; p = 0.03), with a higher proportion of definite VPN cases (92 vs 46%; p = 0.04). Although the clinical manifestations are similar, ESR is an important tool to help distinguish between both conditions. Early nerve biopsy in untreated patients increases diagnostic accuracy, avoiding misdiagnosis.

Changing the Fate of Children with Acute Lymphoblastic Leukemia (ALL) in a Limited Resources Setting

Introduction Pediatric acute Lymphoblastic Leukemia (ALL) patients have about 90% overall survival (OS) in developed countries. However, many children in low-middle income countries (LMIC) do not have access to appropriate drugs at optimal doses, a multidisciplinary medical team, laboratory resources for diagnosis and follow-up, and appropriate support therapy for morbidities and treatment-related toxicities. A 50-60% five-year OS has been reported in children with ALL in Mexico, and our center is not the exception. This low survival rate has pushed Mexican centers to develop strategies highlighting collaboration between centers with economic, research and teaching resources ("Mexico en Alianza con St. Jude MAS"), and outpatient treatment. However, each center must adapt their chemotherapy protocol to its own supplies and possibilities. We report the results of a risk adapted therapy protocol in a limited-resource treatment setting. Materials and Methods All pediatric patients with a diagnosis of ALL from January 2017 to December 2018 were classified according to risk as shown in Figure 1. Depending on risk classification, modifications to the induction, consolidation and intermediate maintenance regimens were made. The higher the risk, the higher the intensity of the regimen, as defined by the number of anthracycline doses, the presence or absence of high-dose methotrexate, and the duration of the consolidation and maintenance phases (Table 1). Demographic data is reported using distribution analysis, and the Kaplan-Meier method is used to analyze and predict overall survival, event-free survival (EFS) and relapse. Our results were compared with previous results from our institution. Results There were 35 male and 25 female patients; median age at diagnosis was 5.5. B-cell and T-cell lymphoblastic leukemia was the diagnosis in 57 (95%), and 3 (5%) patients, respectively, with a follow-up of 16 (8-30) months. Twenty-three (38%), 21 (35%), and 16 (26%) children were classified as high, intermediate and low risk ALL, respectively. After one week of corticosteroids 46 (77%) of patients had a good response. At the end of induction 53 patients had an evaluable MRD (88%), out of which 9 were positive (17%). Median follow-up was 16 (0.6-30) months. Mortality at induction was 6 (10%) patients. Very early relapse was observed in 3(5%) of patients. Estimated 2-year relapse rate was 6%, event-free survival was 84.1%, and OS was 85%. A comparison of results obtained with previous regimens (protocols 1 and 2) and the risk-adapted treatment (protocol 3) is observed in Table 2. Conclusions The implementation of a modified chemotherapy regimen based on adjusted stratification risk was associated to improved responses as reflected by MRD. A decrease in very early relapse rate to 5%, without increasing the toxicity and death during induction was observed. Periodic and prospective outcome evaluation in a limited-resource setting is fundamental to adjust and to standardize therapy. Long-term follow-up of this patient group is required to compare OS and EFS at 5 years. This is a preliminary report, but it seems that we are changing the fate of Mexican children with ALL. Disclosures Gomez-Almaguer: Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

Early combined immunosuppression may be effective and safe in older patients with Crohn's disease: post hoc analysis of REACT.

Physicians may be reluctant to prescribe combined immunosuppression in older patients with Crohn's disease due to perceived risk of treatment-related complications. To evaluate the impact of age on risk of Crohn's disease-related complications in patients treated with early combined immunosuppression vs conventional management in a post hoc analysis of the randomised evaluation of an algorithm for Crohn's treatment (REACT), a cluster-randomised trial. We compared efficacy (time to major adverse outcome of Crohn's disease-related surgery, hospitalisation or serious complications; corticosteroid-free clinical remission) and safety outcomes at 24months, between patients aged <60 vs ≥60years randomised to early combined immunosuppression or conventional management, using Cox proportional hazard analysis or modified Poisson model. In the early combined immunosuppression arm, patients with failure to achieve clinical remission within 4-12weeks of corticosteroids were treated with a combination of tumour necrosis factor-α antagonist plus anti-metabolite and sequentially escalated in a stepwise algorithm. Of 1981 patients, 311 were ≥60years (15.7%; 173 randomised to early combined immunosuppression and 138 to conventional management). Over 24months, 10% of older patients developed Crohn's disease-related complications (early combined immunosuppression vs conventional management: 6.4% vs 14.5%) and 14 patients died (3.5% vs 5.8%). There was no difference between younger and older patients in risk of achieving corticosteroid-free clinical remission (<60years, early combined immunosuppression (72.6%) vs conventional management (64.4%): relative risk [RR], 1.06 [95% CI, 0.98-1.15] vs ≥60years, early combined immunosuppression (74.8%) vs conventional management (63.0%): RR, 1.09 [0.90-1.33], P-interaction=0.78) or time to major adverse outcome (<60years: hazard ratio [HR], 0.71 [0.53-0.96] vs ≥60years: HR, 0.69 [0.31-1.51], P-interaction=0.92) with early combined immunosuppression vs conventional management. We observed no difference in efficacy and safety of early combined immunosuppression compared to conventional management in older and younger patients. Early combined immunosuppression may be considered as a treatment option in selected older patients with Crohn's disease with suboptimal disease control. Clinical Trial Identifier: NCT01030809.

3424 Serial Biomarker Monitoring Predicts Long Term Outcomes in Acute Graft Versus Host Disease

OBJECTIVES/SPECIFIC AIMS: The first aim of the study is to evaluate the accuracy of serum biomarkers of acute GVHD measured after four weeks of corticosteroid therapy to predict 6 month NRM. The second aim of this study is to compare the accuracy of the biomarker algorithm to that of clinical response to corticosteroids after four weeks. The third aim of the study is to develop a novel regression model that uses weekly biomarker measurements over the first month of corticosteroid therapy to predict 6 month NRM. METHODS/STUDY POPULATION:. Patients who received HCT at one of 22 IRB-approved centers and provided blood samples to the Mount Sinai Acute GVHD International Consortium (MAGIC) biorepository and developed GVHD between January 2008 to May 2018 are included in this study. Patients were divided by time into a training set (Jan 2008-Dec 2015, n=233) for model development and a validation set (Jan 2015-May 2018, n=357) to evaluate the predictive performance of the model. The later time of the validation set was chosen deliberately to model contemporaneous GVHD treatment practices. The size of each group was designed so that there would be roughly equal numbers of deaths in both groups. RESULTS/ANTICIPATED RESULTS:. Serum concentrations of GVHD biomarkers after one month of corticosteroid therapy were measured in the validation set, and the predicted probability of NRM ($\hat{\rm p}$) was computed according to the previously published algorithm: $\log[-\log(1 - \hat{\rm p})]=-11.263 + 1.844({\rm logST}2)+ 0.577({\rm logREG}3\alpha)$. The performance of the biomarker algorithm was evaluated by creating receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC) in the validation set. The AUC of the biomarker algorithm was a significantly better predictor of 6 month NRM than clinical response to treatment after four weeks of corticosteroids (0.84 vs. 0.64, p&lt;0.001), which is a clinically relevant improvement in accuracy. To evaluate serial biomarker monitoring, serum biomarker concentrations will be measured weekly at five time points from treatment initiation to one month after corticosteroid therapy. We will use these values in the training set to develop a regression model for 6 month NRM that accounts for repeated biomarker measurements. The performance of this model will be tested in the validation set and the accuracy of the serial biomarker measurements will be compared to the accuracy of measuring biomarkers at the single time point after four weeks of corticosteroid therapy. An AUC improvement of 0.05 would be considered clinically significant. DISCUSSION/SIGNIFICANCE OF IMPACT: Clinical response to treatment after four weeks has been the standard endpoint in GVHD interventional trials for decades. If biomarkers measured at the same time more accurately predict long term mortality, this study would provide the basis for a novel endpoint in GVHD trials and enable more accurate determination of effect size of experimental interventions. An accurate biomarker algorithm will prove useful in guiding immunosuppressive treatment decisions for patients with GVHD. Patients identified by the algorithm as low-risk may benefit from reduced-dose corticosteroid therapy, potentially reducing lethal opportunistic infections. Patients identified as high-risk will be candidates for more intensive immunosuppression or investigational therapies. This precision medicine approach tailors therapy to the individual patient’s biology.

P036 EXPLORING EARLY-RESPONSIVE PHARMACODYNAMIC BIOMARKERS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE (IBD)

The generation of high-quality pilot data that leads to “go/no-go decisions” regarding new or repurposed drugs is often problematic, particularly with a high placebo response rate. In short duration trials, pharmacodynamic (PD) biomarkers can demonstrate proof-of-concept of drug action that may or may not be bridged to clinical outcomes. We sought to identify early-changing PD biomarkers in patients with IBD. Clinical scores and serum were obtained at baseline and after 1–2 weeks of corticosteroids in 5 IBD patients. Using the SOMAscan assay, 45 published chronic steroid and infliximab-responsive proteins were evaluated. All were log-transformed and normality verified using the Shapiro-Wilk test. Pre- to post- treatment comparisons were performed using a paired t-test (p<0.01). Label-free proteome profiling using mass spectrometry was performed. Thirteen proteins responded consistently to 1–2 weeks of corticosteroids. These included biomarkers previously shown to be responsive in pediatric IBD patients after 2 doses of infliximab (CCL23, carnosinase, p-cadherin, CCL25, testican-2, AGT, and FAM3B) and after longer courses of corticosteroid therapy (AGT, afamin, GHBP, CCL22, MMP12, PROT C, Ly9). Four were detected by label-free mass spectrometry (AGT, afamin, PROT C, and carnosinase). Most are involved in regulation of inflammation, immune homeostasis, and extracellular matrix binding. In this small sample, change in some biomarkers correlated with short-term clinical response (carnosinase, testican-2, FAM3B). We have identified treatment-responsive proteins in IBD patients after several weeks of steroids, after 2 doses of infliximab, and within 1–2 weeks of treatment with steroids; these biomarkers may be useful for screening trials of anti-inflammatory drugs. For selection of candidates to study in larger, controlled trials, short-duration biomarker-based trials would be beneficial for patients.

Preformed Complement-Activating Low-Level Donor-Specific Antibody Predicts Early Antibody-Mediated Rejection in Renal Allografts

BACKGROUND.: Donor-specific anti-HLA antibodies (DSA) are a major cause of alloimmune injury. Transplant recipients with negative complement-dependent cytotoxic crossmatch (CDC-XM) and donor cell-based flow cytometric crossmatch (flow-XM) but low level DSA (i.e., by Luminex) have worse outcomes compared with nonsensitized patients. The aim of this study was to establish whether complement-activating ability in this low-level DSA, present before transplantation, as determined by this technique is important in dictating pathogenicity. METHODS.: We retrospectively studied 52 patients with preformed DSA detected by single-antigen flow cytometric fluorescent beads (SAFBs). Patients were transplanted using a steroid-sparing regimen consisting of alemtuzumab induction, 1 week of corticosteroids and tacrolimus monotherapy.Fifteen (29%) of 52 patients experienced antibody-mediated rejection (AMR), whereas 37 (71%) patients did not. There were no demographic differences between patients with AMR and those without. Pretransplant sera were retested using a modified (SAFB) assay, which detects the presence of the complement fragment C4d as a result of DSA-induced complement activation. RESULTS.: C4d+DSA were detected in 10 (19%) of 52 patients. Biopsy-proven AMR occurred in 7 (70%) of the 10 patients with C4d+DSA and in 8 (19%) of 42 patients with C4d-DSA. AMR-free survival was worse in patients with C4d+DSA (P<0.001). CONCLUSIONS.: The ability of preformed, low-level, DSA to trigger C4d fixation in vitro in patients with negative conventional crossmatch tests is predictive for AMR. C4d SAFB is potentially a powerful tool for risk stratification prior to transplantation and may allow identification of unacceptable donor antigens, or patients who may require enhanced immunosuppression.

A Phase Two Randomised Controlled Double Blind Trial of High Dose Intravenous Methylprednisolone and Oral Prednisolone versus Intravenous Normal Saline and Oral Prednisolone in Individuals with Leprosy Type 1 Reactions and/or Nerve Function Impairment

BackgroundLeprosy Type 1 reactions are a major cause of nerve damage and the preventable disability that results. Type 1 reactions are treated with oral corticosteroids and there are few data to support the optimal dose and duration of treatment. Type 1 reactions have a Th1 immune profile: cells in cutaneous and neural lesions expressing interferon-γ and interleukin-12. Methylprednisolone has been used in other Th1 mediated diseases such as rheumatoid arthritis in an attempt to switch off the immune response and so we investigated the efficacy of three days of high dose (1 g) intravenous methylprednisolone at the start of prednisolone therapy in leprosy Type 1 reactions and nerve function impairment.ResultsForty-two individuals were randomised to receive methylprednisolone followed by oral prednisolone (n = 20) or oral prednisolone alone (n = 22). There were no significant differences in the rate of adverse events or clinical improvement at the completion of the study. However individuals treated with methylprednisolone were less likely than those treated with prednisolone alone to experience deterioration in sensory function between day 29 and day 113 of the study. The study also demonstrated that 50% of individuals with Type 1 reactions and/or nerve function impairment required additional prednisolone despite treatment with 16 weeks of corticosteroids.ConclusionsThe study lends further support to the use of more prolonged courses of corticosteroid to treat Type 1 reactions and the investigation of risk factors for the recurrence of Type 1 reaction and nerve function impairment during and after a corticosteroid treatment.Trial RegistrationControlled-Trials.comISRCTN31894035

Longitudinal study of anti-myeloma treatment patterns in a U.S. commercial population before and after approval of bortezomib (BOR).

e18533 Background: During the past decade, the IMiDs [thalidomide (THA) and lenalidomide (LEN)] and BOR received FDA approval for multiple myeloma (MM). Our objectives were to characterize treatment patterns before and after introduction of BOR in 6/2003. Methods: This was a retrospective cohort study using enrollment and claims data from a large managed care organization with an annual enrollment ranging from 9-15 million. Patients ≥ 18 years with MM, newly diagnosed between 7/1/2000 and 12/31/2007, and treated with anti-MM therapies were included. Patients were identified by ICD-9-CM diagnosis code and followed from diagnosis to end of continuous enrollment or 12/31/2008. Anti-MM regimens were defined as sequentially administered groups of anti-neoplastic drugs or stem cell transplant (SCT) procedure(s) identified from Rx and medical claims and grouped into mutually exclusive regimens: SCT, BOR, THA, LEN, ALK (melphalan or cyclophosphamide), VIN (vincristine) or STE (≥ 6 weeks of corticosteroids). Results: 2,210 patients were included. The mean age was 59.9 yrs; 44.5% were female. 29.4% and 70.6% were diagnosed pre and post 6/2003. Patients received a mean of 2.16 regimens (med: 2; range 1-18) over 1.68 years of follow up (SD= 1.29). 40.3% of the patients died by the death file cutoff date 2/2009. Regimens most commonly used are shown below (Table). Conclusions: After 6/2003, THA and SCT displaced VIN and ALK as most frequently administered 1st line or 2nd line therapies. BOR and LEN displaced STE and VIN as 3rd line therapy. Line oftherapy Pre 6/2003 Post 6/2003 N % N % 1 650 STE 21.8 ALK 21.4 VIN 18.2 THA 14.9 1,560 THA 26.3 STE 21.8 SCT 13.3 VIN 9.4 2 312 THA 27.2 STE 19.2 VIN 17.9 SCT 12.8 809 THA 27.3 STE 19.4 SCT 12.7 BOR 12.4 3 170 THA 33.5 STE 19.4 SCT 12.9 VIN 10.0 429 THA 23.8 BOR 19.6 STE 14.7 LEN 13.3 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck Merck

Hepatitis B Virus-Associated Polyarteritis Nodosa

Hepatitis B virus-associated polyarteritis nodosa (HBV-PAN) is a typical form of classic PAN whose pathogenesis has been attributed to immune-complex deposition with antigen excess. We conducted the current study to 1) analyze the frequency of HBV infection in patients with PAN, in light of the classification systems described since 1990; 2) describe the clinical characteristics of HBV-PAN; 3) compare the evolution according to conventional or antiviral treatment; and 4) evaluate long-term outcome. One hundred fifteen patients were included in therapeutic trials organized by the French Vasculitis Study Group and/or referred to our department for HBV-PAN between 1972 and 2002. To determine the frequency of HBV-PAN during the 30-year period, we analyzed a control group of patients with PAN without HBV infection, followed during the same period and diagnosed on the same bases. Depending on the year of diagnosis, different treatments were prescribed. Before the antiviral strategy was established, some patients were given corticosteroids (CS) with or without cyclophosphamide (CY). Since 1983, treatment for patients with HBV markers has combined 2 weeks of CS followed by an antiviral agent (successively, vidarabine, interferon-alpha, and lamivudine) combined with plasma exchanges (PE).Ninety-three (80.9%) patients entered remission during this period and 9 (9.7%) of them relapsed; 41 (35.7%) patients died. For the 80 patients given the antiviral strategy as intention-to-treat, 4 (5%) relapsed and 24 (30%) died vs 5 (14.3%) relapses (not significant [NS]) and 17 (48.6%) deaths (NS) among the 35 patients treated with CS alone or with CY or PE. HBe-anti-HBe seroconversion rates for the 2 groups, respectively, were: 49.3% vs 14.7% (p < 0.001). Patients who seroconverted obtained complete remission and did not relapse.Thus, HBV-PAN, a typical form of classic PAN, can be characterized as follows: when renal involvement is present, so is renal vasculitis; glomerulonephritis due to vasculitis is never found; antineutrophil cytoplasmic antibodies (ANCA) are not detected; relapses are rare, and never occur once viral replication has stopped and seroconversion has been obtained. Combining an antiviral drug with PE facilitates seroconversion and prevents the development of long-term hepatic complications of HBV infection. The major cause of death is gastrointestinal tract involvement. Importantly, the frequency of HBV-PAN has decreased in relation to improved blood safety and vaccination campaigns.