Expression of EGF receptor (EGFR) is frequently elevated in squamous cell carcinoma of the head and neck (SCCHN). Cetuximab is an anti-EGFR monoclonal antibody that has been shown to improve overall survival in patients with locally advanced SCCHN when combined with radiotherapy. Data from Phase II trials suggest an interesting activity of cetuximab in patients with recurrent or metastatic SCCHN who are refractory to cisplatin. The Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer (EXTREME) Phase III trial compared platin-5-fluorouracil alone versus combined with cetuximab as first-line treatment in recurrent or metastatic SCCHN. In the cetuximab arm of this study, a significant improvement in the overall survival (the main objective), progression-free survival and response rate were observed. The quality of life analyses (QLQ-C30 and QLQ-H&N35) showed no significant differences in most of the studied scores between the two treatment arms. Nevertheless, patients in the cetuximab arm displayed significant improvements in pain, swallowing problems and scores for speech and social eating problems. The results of the EXTREME study (and other studies evaluating cetuximab for the treatment of SCCHN) suggest a lack of a predictive value for the expression of EGFR (determined by immunohistochemistry) by the tumor and other biomarkers need to be investigated. The role of other targeted drugs and of possible combinations of these new drugs with cetuximab should be investigated in properly designed preclinical studies and clinical trials.

Background and objectives Because of its beneficial off‐target effects against non‐mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID‐19). Using samples from participants in a placebo‐controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID‐19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS‐CoV‐2. Methods This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID‐19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ‐irradiated SARS‐CoV‐2‐infected or mock‐infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single‐cell immunophenotyping was made by flow cytometry. Results BCG vaccination, but not placebo vaccination, reduced SARS‐CoV‐2‐induced secretion of cytokines known to be associated with severe COVID‐19, including IL‐6, TNF‐α and IL‐10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4+ and CD8+ T cells, and an activation of eosinophils in response to SARS‐CoV‐2. Conclusions The immunomodulatory signature of BCG’s off‐target effects on SARS‐CoV‐2 is consistent with a protective immune response against severe COVID‐19.

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Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory condition impacting multiple organ systems.1,2SLE affects approximately 1.5 million Americans, disproportionately females of reproductive age, and is more prevalent in non-Caucasian populations.3Fatigue and pain are some of the most prominent symptoms of SLE, contributing to the heavy disease burden and disruption to daily life.4This study aimed to further understand the burden of SLE. Lilly worked with the Lupus Foundation of America (LFA) and Evidera to develop the SLE-UPDATE (Understanding Preferences, Disease Activity and Treatment Expectations) survey.Objectives:To understand the patient-perceived symptom burden of SLE, in particular pain and fatigue, within the current landscape of therapeutic options. This study also focused on current treatment patterns in SLE patients.Methods:This was a cross-sectional, non-interventional, online survey study conducted in partnership with the LFA. English-speaking United States patients aged ≥18 years with a self-reported diagnosis of SLE completed the survey following online screening and informed consent. Descriptive data are presented by means (standard deviation [SD]) for continuous measures, and frequency (n, %) for dichotomous measures. Demographic, clinical, and patient-reported outcomes were collected including the FACIT-Fatigue (range 0-52, higher scores indicate less fatigue), Pain Numerical Rating Scale (NRS) (0 [none] to 10 [worst imaginable]), Worst Joint Pain NRS (0 [none] to 10 [worst imaginable]), and the LupusPRO, a validated, lupus-specific quality of life (QoL) instrument (range 0-100, higher scores indicate better QoL).Results:A total of 500 patients with SLE completed the survey. Patients were predominantly female (75%), white/Caucasian (76%), with a mean age of 42.6 years and mean disease duration of 11.1 years.Most patients with SLE rated their overall condition as either good (38%) or fair (31%), with 8% rating poor and 7% excellent. Current non-biologic prescription medication use included: antimalarials 42%, corticosteroids 33%, immunosuppressants 33%, nonsteroidal anti-inflammatory drugs (NSAID) 32%, other analgesics 15% and 10% were using tofacitinib. Biologic therapies were being used by only 19%, including intravenous (IV) Benlysta (37%),subcutaneous(SC) Benlysta (25%), rituximab (17%), and 22% were using other biologics. Fatigue was the most commonly reported symptom (69%), with 40% of patients ranking fatigue as their most bothersome SLE symptom. Forty eight percent of patients with current fatigue rated the severity as moderate and 33% as severe. The mean (SD) FACIT-Fatigue score was 22.9 (12.0). The next most commonly reported symptoms were joint stiffness (57%), sleep problems (55%), joint pain/swelling (53%), and muscle pain (52%). Sixty percent of patients reported experiencing pain all or most of the time over the past seven days. A total of 30% of patients with current joint pain/swelling rated it as severe, and 24% of patients with current joint stiffness rated it as severe. The mean scores for Worst pain NRS and Worst Joint Pain NRS were both 5.8 out of 10.The LupusPRO domains indicated by respondents as the most impacted by SLE were Emotional Health, Pain/Vitality, and Lupus Medications.Conclusion:Fatigue, followed by pain and joint stiffness, were the most common patient-reported symptoms contributing to the overall SLE disease burden. Further research could highlight the efforts required to address the inadequacies in treatment and management of pain and fatigue in this patient population.Disclosure of Interests:Julie Birt Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Monica Hadi: None declared, Nashmel Sargalo: None declared, Ella Brookes: None declared, Paul Swinburn: None declared, Leslie Hanrahan: None declared, Karin Tse: None declared, Natalia Bello Vega Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Kirstin Griffing Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Maria Silk Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Laure Delbecque Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Diane L Kamen Consultant of: Consulted on SLE survey development for Lilly and consulted on SLE trial protocol development for EMD Serono in 2019

BackgroundThe Fibromyalgia Rapid Screening Tool (FiRST) has been proposed as a self reported screening questionnaire comprising only 6 questions for detection of fibromyalgia (FM)1. A patient is considered FM in case of answering “yes” at least 5 out of the 6 questions. Such questionnaire is independent from tender points at physical examination and, therefore, of particular interest in Spondyloarthritis (SpA) patients.ObjectivesTo evaluate the FiRST questionnaire validity and reliability in a SpA population.MethodsPatients: SpA patients (according to the rheumatologist) consecutively consulting at the rheumatology department of a tertiary care university hospital. Data collection: Apart from the FiRST questionnaire other variables were collected: a) Demographics: age, gender. b) SpA characteristics: clinical, imaging and treatment. c) Other collected data: history of depression and the consumption (ever) of psychotropic medication (e.g antidepressants, myorelaxants, anxiolytics, strong opioids). Statistical analysis: The following was evaluated: a) percentage of patients answering “yes” to ≥5/6 questions (here referred as FM+); b) classification performance of each question of the FiRST by assessing the positive likelihood ratio (LR+); c) percentage of patients with history or current intake of psychotropic medication and history of depression in FM+ and FM-groups respectively (χ2); d) reliability of the questionnaire was assessed by the prevalence – adjusted bias – adjusted kappa statistics (PABAK) in 22 patients in two consecutive visits with stable disease activity and no treatment changes.ResultsOf the 222 patients who completed the questionnaire, 195 were retained for our analysis and 42 (21.5%) patients were classified as FM+. The LR+ per question was 4.3 [CI 95% 2.85; 6.43], 1.8 [CI 95% 1.52; 2.07], 2.7 [CI 95% 2.17; 3.42], 3.4 [CI 95% 2.44; 4.59], 2.6 [CI 95% 1.99; 3.40] and 2.1 [CI 95% 1.80; 2.51] for questions 1 to 6 respectively; suggesting that question 1 performed the best. The percentage of patients with either history of depression or consumption of psychotropic medication was significantly higher in the FM+ group (67%vs.36%, p≤0.01). Concerning the reliability, agreement was good with a PABAK=0.64 (0.314; 0.958).ConclusionsThis study suggests: 1) the acceptable simplicity, feasibility and reliability of the FiRST questionnaire in clinical practice; 2) potentially the first question related to full body pain might be the most relevant; 3) the good external validity of FiRST when considering the higher percentage of patients with either history of depression or consumption of psychotropic medications. Such tool might facilitate the management of SpA in daily practice.ReferencesPerrot S, Bouhassira D, Fermanian J. Development and validation of the Fibromyalgia Rapid Screening Tool (FiRST). Pain 150, 250–256 (2010).AcknowledgementsN.B wishes to acknowledge to the Spanish Rheumatology Foundation (FER) for a training bursary.Disclosure of InterestNone declared

BackgroundFibromyalgia (FM) can coexist with Spondyloarthritis (SpA) leading to diagnostic and treatment dilemmas, especially in the presence of enthesitis. The Fibromyalgia Rapid Screening Tool (FiRST) is a self-reported questionnaire, independent from tender points, which can be used for FM screening1.ObjectivesTo estimate the prevalence of FM in a SpA cohort according to the FiRST, to compare the prevalence of FM with regard to the fulfilment of the ASAS classification criteria, to compare the clinical/disease features and TNFi treatment in terms of initiation and first TNFi retention rate, in patients with/without FM respectively.MethodsPatients: SpA patients (according to the rheumatologist) consecutively consulting on a tertiary care hospital. FM definition: according to the FiRST questionnaire, patients answering “yes” at ≥5/6 questions were considered FM+. Data collection: All patients completed the FiRST questionnaire. Demographics, patients/disease characteristics, activity/severity and TNFi initiation as well as the retention of the first TNFi treatment, were collected. Statistical analysis: The percentage of FM+ according to the FiRST was calculated in the global population and in the different arms of the ASAS criteria. Demographics, disease characteristics, activity and severity were compared in FM+ and FM- groups. The percentage of patients ever initiating a TNFi was compared in both groups. The retention rate of the first TNFi in both groups was estimated by Kaplan-Meier curves and tested by the Log-rank test. Predisposing factors for first TNFi retention rate were estimated by Cox models.ResultsOf the 222 patients who completed the FiRST questionnaire, 195 were included for the analysis, among them 42 (21.5%) fulfilled the FM definition. From the total, 185 (94.8%) met the ASAS criteria with a similar % of FM in the different subgroups [e.g imaging (21.5%) and clinical (18.7%), p=NS]. Patients fulfilling the FM definition presented with more enthesitis (59.5% vs.39.5%, p=0.02), more frequent history of depression (41.0% vs.18.4%, p<0.01), higher total BASDAI [4.6 (±2.3) vs. 2.6 (±2.0), p<0.01] and BASFI [4.8 (±3.7) vs. 2.0 (±1.5), p<0.01]. Furthermore, patients in this group reported more frequently analgesics (92.7%vs.72%, p<0.01) and psychotropic medications (e.g. myorelaxant or antidepressants or anxiolytic or strong opioids) (66.7%vs.35.9%,p<0.01). Regarding TNFi treatment, TNFi were initiated in 79%vs.70% in FM+ and FM- groups, respectively (p=NS). The retention rate of the first TNFi was significantly shorter in the FM+ group. After 1 and 2 years, 55%vs.50% and 28.1%vs.41.2% of patients were still under treatment in the FM+vs.FM- groups, respectively,(Cox p=0.03).ConclusionsOur study suggests the following:1) the similar percentage of FM in the imaging and clinical arms of the ASAS criteria is an argument in favor of the validity of these criteria; 2) the coexistance of FM might impact the score of the instrument used to evaluate disease activity and also the retention rate of the TNFi treat...

R0 resections after IC and before RT could indicate an improvement in OS in patients with T4b-SCHNC that obtain less than a 90% PR at primary after IC. We consider that this approach deserves further research in prospective clinical trials.

Background:SLE is managed by variable combinations of five drug classes: antimalarials, biologics, corticosteroids, non-steroidal anti-inflammatory agents, and immunosuppressants. Opioids are commonly prescribed to SLE patients despite not being effective for the management of long-term musculoskeletal pain.1Objectives:To describe corticosteroid and opioid use among SLE patients in the United States, and the impact of belimumab initiation on prescribing patterns.Methods:This retrospective study used MarketScan administrative claims databases to select insured adults, age ≥18, with a diagnosis (ICD-9/10 710.0 & M32) of SLE between 1/1/2012 and 5/31/2018 (earliest SLE diagnosis = index date). Patients were followed from index through the earliest of health plan disenrollment or 5/31/2019 (minimum of 12 months). Corticosteroid use was measured in the 12 months following SLE index date. Average daily dose of oral corticosteroids in prednisone equivalents was measured for 12 months after corticosteroid initiation. Opioid use was measured overall, and by strength and length of treatment (chronic use defined as >90 days of supply). Oral corticosteroid and opioid use were compared in the 6 months before and after initiation of belimumab.Results:Of 49,413 SLE patients eligible for analysis, mean [SD] age was 50.1 [14.0] years, 90.2% were female, and average follow-up was 3.6 [1.9] years. 89.8% of patients received any SLE treatment and 68.5% received corticosteroids. The average number of corticosteroid prescriptions was 4.6 [4.1] during 12 months of follow-up. 52.6% of patients had ≥1 claim for an opioid prescription in the 12 months after SLE index and 34.6% were identified as having chronic opioid treatment. Among patients with oral corticosteroid treatment and 12 months of study enrollment post-corticosteroid initiation, the average daily dose for oral corticosteroids was 19.4 [14.2] mg and 59.6% had a high average daily dose of >15mg (Figure 1). Among 1,710 patients with belimumab treatment and 6 months of study enrollment after the first prescription, use of oral corticosteroids decreased by 9.1% (p=0.001), average daily dose decreased from 14.5 [18.4] mg to 11.9 [18.0] mg (p<0.001) in the 6 months post initiation as compared to the 6 months prior. However, 48.6% of patients remained on a medium (7.5mg – <15mg) or high dose (≥15mg). Initiation of belimumab resulted in no change in opioid use (Table 1).Table 1.Before BelimumabAfter Belimumabp-value, pre vs.(N =1,710)(N =1,710)post BelimumabPatients with an oral steroid prescription (N, %)1,24272.6%1,08663.5%0.001Number of prescriptions (Mean, SD)2.32.32.12.3<0.001Average daily dose (Mean, SD)14.518.411.918.0<0.001Low average daily dose (>0 to <7.5 mg) (N, %)21012.3%25514.9%0.037Medium average daily dose (7.5 - <15 mg) (N, %)38922.7%33419.5%0.041High average daily dose (15 mg or more) (N, %)64337.6%49729.1%<0.001Patients with an opioid prescription (N, %)90152.7%86150.4%0.341Weak opioids35620.8%31218.2%0.089Strong opioids69940.9%69540.6%0.915Acute Opioid Use53859.7%48656.4%0.165Chronic opioid use36340.3%37543.6%0.165Conclusion:These results suggest that a strikingly high proportion of patients with SLE are treated with corticosteroids to control the disease and opioid therapy to manage chronic pain. While there was no change in opioid use, corticosteroid use decreased following initiation of belimumab.References:[1]Chen SK, Feldman CH, Brill G, et al. Use of prescription opioids among patients with rheumatic diseases compared to patients with hypertension in the USA: a retrospective cohort study. BMJ 2019;9:e027495Disclosure of Interests: :Julie Birt Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jianmin Wu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Kirstin Griffing Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Natalia Bello Vega Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Nicole Princic Employee of: I work for IBM Watson Health who was paid by Eli Lilly who funded this research., Isabelle Winer Employee of: I work for IBM Watson Health who was paid by Eli Lilly who funded this research., Carolyn Lew Employee of: I work for IBM Watson Health who was paid by Eli Lilly who funded this research., Karen Costenbader Grant/research support from: Merck, Consultant of: Astra-Zeneca