Management of autoimmune complications in patients with lymphoid cancer

Autoimmune conditions can occur at any temporary relationship with malignant lymphomas. In many instances, treatment at diagnosis is not required, but symptomatic autoimmune conditions represent an indication for treatment particularly in chronic lymphoproliferative diseases. Treatment is selected depending on the predominant condition - autoimmune disease (immunosuppression) or lymphoma (anti-lymphoma therapy). Steroids as well as anti-CD20 antibodies are effective against both and may suppress the autoimmune complication for a prolonged period. Efficacy of B-cell receptor inhibitors has provided us with novel insights into the pathophysiology of antibody-producing B-cells. Screening for underlying autoimmune conditions is part of the lymphoma work-up since other drugs like immunomodulators or checkpoint inhibitors should be avoided or used with caution. Here we discuss diagnostic challenges and treatment approaches for different situations involving lymphomas and autoimmune cytopenias.

Liver and kidney function in patients with Covid-19 treated with remdesivir

For the treatment of Covid-19 patients with remdesivir, poor renal- and liver function were both exclusion criteria in randomized clinical trials (RCTs) and contra-indication for treatment. Also, nephrotoxicity and hepatotoxicity are reported as adverse events. We retrospectively reviewed renal- and liver functions of covid-19 patients who received remdesivir in the 15 days after treatment initiation. Approximately 20% of the patient population met RCT exclusion criteria. In total, 11% of the patients had a decrease in estimated glomerular filtration rate larger than 10 ml/min/1.73m2. Also, 25% and 35% had increased alanine transaminase and aspartate transaminase levels, respectively. However, serious adverse events were limited. Therefore, contra-indications based on kidney- and liver function should not be absolute for remdesivir treatment in patients with Covid-19 if these functions are monitored regularly.

The effect of TEE on treatment change in patients with acute ischemic stroke

Background and purpose Ischemic stroke is a widespread disease carrying high morbidity and mortality. Transesophageal echocardiography (TEE) is considered an important tool in the work-up of patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients; its utility is limited by a semi-invasive nature. The purpose of this study was to evaluate the probability of treatment change due to TEE findings (yield) in the work-up of AIS and TIA patients. Methods Retrospective data on patients with AIS or TIA who underwent TEE examination between 2000–2013 were collected from the institutional registry. Results The average age of 1284 patients who were included in the study was 57±10.4, 66% of patients were male. The most frequent TEE findings included aortic plaques in 54% and patent foramen ovale (PFO) in 15%. TEE findings led to treatment change in 135 (10.5%) patients; anticoagulant treatment was initiated in 110 of them (81%). Most common etiology for switch to anticoagulation was aortic plaques (71 patients); PFO was second most common reason (26 patients). Significant TEE findings (thrombus, endocarditis, tumor) were found in 1.9% of patients, they were more common in young patients (<55; 56% of the patients). Conclusions The beginning of anticoagulation treatment in patients with thick and complicated plaques was found frequently in our study. Significant TEE findings, were infrequent, constituted an absolute indication for treatment change and were more common in younger patients.

Recanalization and Stenting of the Celiac and the Superior Mesenteric Artery Supported by Use of a Steerable Introducer Sheath: Report on 2 Years’ Experience

Purpose: To compare technical parameters and success of recanalization of celiac (CA) or superior mesenteric artery (SMA) with usage of steerable vs not steerable introducer sheaths. Methods: A retrospective analysis was performed on all consecutive patients who underwent recanalization with stent implantation of CA or SMA between 2015 and 2019. Data regarding technical success (successful stent placement with restoration of sufficient blood flow by the first attempt without changing kind of introducer sheath or access site), indication for treatment, vascular access, kind of introducer sheath, fluoroscopy time and radiation dose were collected. Preinterventional CT were analyzed to classify the difficulty of catheterization of target vessels. Technical parameters were compared with independent t-test (p ≤ 0.05). Results: 66 patients underwent recanalization of CA or SMA. Usage of steerable introducer sheaths was associated with higher technical success compared to not steerable introducer sheaths with transfemoral approach respectively of 8/8 vs 15/19 for the CA and 11/11 vs 17/20 for the SMA. Steerable introducer sheaths were used in recanalization considered more technically difficult compared to not steerable introducer sheaths (58% vs 33%). Usage of steerable introducer sheath showed a statistically significant reduction of radiation dose in the recanalization of the SMA (respectively 32035 ± 15716 cGy cm2 vs 60102 ± 28432 cGy cm2; p = 0.005). Conclusion: Even if used in more difficult interventions, steerable introducer sheaths showed a higher technical success compared to not steerable introducer sheaths with transfemoral access.

Neuropathy with IgM Gammopathy: Incidence, Characteristics and Management, a Rory Morrison W.M.U.K Registry Analysis

Background IgM paraprotein-associated peripheral neuropathies (PN) are a heterogenous group of disorders seen in patients with IgM MGUS and Waldenström's Macroglobulinaemia (WM). Anti-myelin associated glycoprotein (MAG) antibodies are causally identified in ~50% of such cases, but other neuropathies with other IgM-targets are described, along with AL amyloidosis and cryoglobulinaemic vasculitis amongst others. Presence of neuropathy alone is typically not an indication for treatment, but progressive disability is. Due to their relative rarity and heterogeneity, the true prevalence and optimal management of these neuropathies is currently unclear. Methods The Rory Morrison WMUK Registry, a national IgM-related disorders database incorporating 18 centres, was searched for all patients with PN and retrospective data clinical data extracted. Research ethics approval was obtained. Results IgM-related PN was identified 153 patients, of whom 99 (64.7%) had underlying WM and 54 (35.3%) had IgM MGUS. Anti-MAG neuropathy was present in 83 (54.6%) patients, anti-ganglioside in 3 (2%), AL amyloid in 7 (4.3%), cryoglobulinemia in 6 (3.7%), one (0.6%) case of CANOMAD syndrome, and a non-MAG IgM-neuropathy in 53 (34.5%%). PN was present at diagnosis in 143 (93.5%) whereas 10 (6.5%) were diagnosed during the course of their disease. Median age at diagnosis was 64 years (30-92) and 101/153 (66%) were male. Table 1 details results at diagnosis. κ-light chain was present in 80.3%, λ in 11.8% and 7.9% had multiple M-protein bands expressing both light chains. MYD88L265P was identified in 44/55 tested patients (80%) and in 23/30 (76.7%) cases of anti-MAG. In those with an IgM-related disorder, 13/20 (65%) had MYD88L265P, higher than in other IgM MGUS patients (7/14, 50%). CXCR4MUT were found in 3/22 (13.6%). Median bone marrow infiltration on trephine was 13% (range 0-85%), but 10 patients had no evidence of disease, 5 had disease on flow cytometry only, 2 an isolated finding of MYD88L265P and 1 isolated CXCR4MUT on PCR. IgM-related PN was seen in 99/719 (13.8%) of all registry patients with WM. At diagnosis, the bone marrow burden, M-protein and B2M were all significantly lower (p&lt;0.001) than in those with WM without PN, despite identical median age. Therapy had been required in 81 (53.3%) patients, including at time of diagnosis in 23 (15%). Median time from diagnosis to treatment was long, at 6.7 years (95% CI 3.2-9.1 years). PN was the sole treatment indication in 64/81 (79%) cases. Time to treatment commencement did not appear to be affected by M-protein quantity or marrow burden, but patients with WM were more likely to have received treatment for their PN (59/108, 54.6%). Frontline treatment incorporated rituximab (R) in 66/81 (81.5%) patients, including R-monotherapy in 30, DRC 20, R-CHOP/R-CVP eight and BR in seven. A major biochemical response was seen in 19/34 (55.9%) patients. Clinical response was seen in 34 of 45 evaluable cases (75.6%), with improvement in 13 (28.9%) and stabilisation in 21 (46.7%). Clinical response or stabilisation was significantly more likely with R-containing therapy (82.1% vs 33.3%, p 0.04), non-amyloid related PN (82% vs 0%, p = 0.01) and attainment of ≥ partial response. All patients (n=12) with normal BMAT or isolated MYD88L265P responded to R-containing frontline therapy, another positive prognostic factor (p = 0.08). Progression of PN occurred after an initiation period of clinical response in 7/34 (20.5%), necessitating re-treatment at a median of 4.3 years after frontline therapy. Median time to 2nd line therapy was 6.7 years, longer than for other WM treatment indications (p = 0.04). Conclusions IgM-related PN is a cause of morbidity for a significant proportion of patients with WM, with a prevalence of 13.7%. However, a third of cases occur in those with IgM MGUS and even very small clonal populations seem capable of causing disease but appear responsive to rituximab therapy. Patients typically have comparatively low systemic disease burden and low rates of CXCR4MUT, perhaps representing a more indolent phenotype or a product of earlier diagnosis. PN is frequently the sole indication for treatment, reflecting this. Clinical improvement or stabilisation was seen in 75% of treated patients, and attainment of ≥50% reduction in IgM (PR) and treatment with rituximab is associated with a more favourable outcome, whereas AL amyloid neuropathy appears to be more treatment resistant. Disclosures Lindsay: Amgen: Other: Travel Expenses; Takeda: Honoraria, Other: Travel Expenses; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses. Carr:Lupin: Honoraria; CSL: Honoraria; Grifols: Other: Travel support. McCarthy:Janssen: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees. El-Sharkawi:Roche: Other: Conference fees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Pratt:Binding Site Ltd: Other: Personal fees; Amgen: Other: Personal fees; Janssen: Other: Personal fees; Celgene: Other: Personal fees; Takeda: Other: Personal fees; Gilead: Other: Personal fees; Sanofi-Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. D'Sa:Janssen: Honoraria, Research Funding; Sanofi: Honoraria; BeiGene: Honoraria, Research Funding.

1339. Antibiotic Prescribing Varies among Patients with a Documented Penicillin or Cephalosporin Adverse Drug Reaction

Background Studies have shown that over half of hospitalized children receive an antibiotic during their encounter, of which between 30-50% is considered inappropriate. Antibiotic prescribing is further complicated as approximately 10% of children are labeled beta-lactam allergic, resulting in the use of either broad-spectrum or suboptimal therapy. The purpose of this study was to compare antibiotic prescribing between patients with a documented ADR vs. those without using a nationwide sample of hospitalized children. Methods We performed a point prevalence study among 32 hospitals between July 2016-December 2017 where data were collected via chart review on pediatric patient and antimicrobial characteristics, including the indication for all antimicrobials. In additional, ADR history data were collected on which antimicrobial(s) were documented (e.g., penicillin, cephalosporins). Patients were mutually assigned into either: 1) no documented ADR; 2) penicillin ADR-only; 3) cephalosporin ADR-only; and 4) ADR for both penicillin and cephalosporin. The distribution of antibiotics were compared between the ADR groups, stratified by the indication for treatment. Results A total of 12,250 pediatric patients (17,929 antibiotic orders) who were actively receiving antibiotics were identified. A history of penicillin and cephalosporin ADR was documented in 5.5% and 2.8% of these patients, respectively. When compared to patients with no documented ADR, penicillin ADR patients were more likely to receive a fluoroquinolone for a SSTI infection (odds ratio [OR]: 5.6), surgical prophylaxis (OR: 18.8) or for surgical treatment (OR: 5.2) (see Figure). Conversely, penicillin ADR patients were less likely to receive first-line agents, such as narrow-spectrum penicillin for bacterial LRTI (OR: 0.08) and piperacillin/tazobactam for GI infections (OR: 0.22). Cephalosporin ADR patients exhibited similar patterns with increased use of carbapenems and fluoroquinolones when compared to patients with no ADR. Figure 1: Odds of Receiving Select Antimicrobials Among PCN ADR Patients When Compared to Non-ADR patients, by Indication Conclusion A large, nationwide sample of pediatric patients who were actively prescribed antibiotics helped identify several diagnoses where comprehensive guidelines for appropriate ADR prescribing and increased ADR de-labeling initiatives are needed to ensure optimal treatment. Disclosures Brian R. Lee, MPH, PhD, Merck (Grant/Research Support) Jason Newland, MD, MEd, FPIDS, Merck (Grant/Research Support)Pfizer (Other Financial or Material Support, Industry funded clinical trial)

High Effectiveness of a 14-Day Concomitant Therapy for Helicobacter pylori Treatment in Primary Care. An Observational Multicenter Study

Background: The current cure rates with triple therapy combining a proton-pump inhibitor, amoxicillin and clarithromycin are unacceptably low. Aims: To evaluate the efficacy of a 14-day concomitant therapy as an empirical first-line treatment for curing Helicobacter pylori (Hp) infection in primary care. Methods: Patients from six primary care centers in Catalonia -Spain- were included consecutively. Hp status pre and post treatment was assessed according to local clinical practice protocol. A 14-day concomitant therapy (amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg plus omeprazole 20 mg, all drugs administered twice daily) was prescribed. Adherence to therapy and adverse events were assessed by personal interview. Results: 112 patients were enrolled. Mean age was 46.7 ± 16.1 years. Main indication for treatment was non-investigated dyspepsia (83%). Hp eradication was achieved in 100 of the 112 patients. Eradication rates were 89.3% (95% CI: 81.7–94.1) by intention-to-treat (ITT) analysis and 91.7% (95% CI; 84.6–95.9) per protocol (PP). No major side effects were reported; 104 (92.8%) patients complete the treatment. Forty-seven patients (42%) complained of mild side effects (metallic taste, nausea). Low adherence to treatment (p = 0.004) and significant adverse events (p = 0.004) were the variables associated with treatment failure. Conclusions: In primary care, a 14-day concomitant therapy is highly effective and well tolerated.

SAT0478 OSTEOPOROSIS TREATMENT IN PORTUGUESE PATIENTS WITH PSORIATIC ARTHRITIS – WHAT IS THE VALUE OF THE FRACTURE RISK ASSESSMENT TOOL (FRAX)?

Background:Few studies have evaluated the prevalence and treatment of osteoporosis (OP) in patients with psoriatic arthritis (PsA), and many of these patients are not screened using dual-energy X-ray absorptiometry (DXA). FRAX makes it possible to stratify the risk and define which patients may benefit from anti-osteoporotic treatment, but its usefulness in this population is not well established.Objectives:The aim of this study was to determine whether the application of FRAX changes the indication for anti-osteoporotic treatment in PsA patients, according to the Portuguese guidelines.Methods:In this cross-sectional study, we evaluated PsA patients from a tertiary hospital, registered in a national database (Reuma.pt), aged between 40 and 90 years and with a last consultation in 2019. FRAX was applied in all of them, regardless of being under anti-osteoporotic treatment and, when DXA was available, the femoral neck bone mineral density was used. Patients were stratified according to the risk of fracture, and those at high risk were considered candidates for anti-osteoporotic treatment, according to national guidelines [FRAX ≥11% for major osteoporotic fracture (MOF) or ≥ 3% for hip fracture (HF) without DXA; FRAX ≥9% for MOF or ≥ 2.5% for HF, with DXA].Results:We included 100 patients, 52 females, with a mean age of 54,4 ±8,9 years and a median disease duration of 10 (6-17) years. Only 43 had already performed DXA and 6 had OP according to World Health Organization criteria. Seven patients were identified as having a high risk of fracture; applying femoral neck bone mineral density, 2 more patients with indication for treatment were recognized, totalizing 9 patients. There was a low agreement between the indication for treatment based only on DXA and FRAX (Cohen’s k 0.066). There was a moderate and significant correlation between percentage of risk of MOF by FRAX with and without DXA (Spearman’s ρ 0.804, p <0.001); for the risk of HF by FRAX with and without DEXA the correlation was weaker but still significant (Spearman’s ρ 0.439, p = 0.004). There was no association between the indication for treatment by FRAX and the performance of DXA (chi-square test, p = 0.597), nor the fact of performing DXA significantly affected the risk of MOF (Wilcoxon test, p = 0.185) or of HF (Wilcoxon test, p = 0.785) by FRAX.Conclusion:In line with Portuguese guidelines, FRAX seems to be, in itself, a very useful tool in patients with PsA, and the performance of DXA does not significantly alter the indication for anti-osteoporotic treatment.References:[1]Rodrigues AM, Canhao H, Marques A, Ambrosio C, Borges J, Coelho P, et al. Portuguese recommendations for the prevention, diagnosis and management of primary osteoporosis - 2018 update. Acta Reumatol Port. 2018;43(1):10-31.[2]Del Puente A, Esposito A, Parisi A, Atteno M, Montalbano S, Vitiello M, et al. Osteoporosis and psoriatic arthritis. J Rheumatol Suppl. 2012;89:36-8.[3]Gulati AM, Michelsen B, Diamantopoulos A, Grandaunet B, Salvesen O, Kavanaugh A, et al. Osteoporosis in psoriatic arthritis: a cross-sectional study of an outpatient clinic population. RMD Open. 2018;4(1):e000631.[4]Adami G, Fassio A, Rossini M, Caimmi C, Giollo A, Orsolini G, et al. Osteoporosis in Rheumatic Diseases. Int J Mol Sci. 2019;20(23).[5]Kanis JA, Harvey NC, Johansson H, Oden A, Leslie WD, McCloskey EV. FRAX Update. J Clin Densitom. 2017;20(3):360-7.Disclosure of Interests:Filipe Pinheiro: None declared, Maria Rato: None declared, Bruno Miguel Fernandes: None declared, Salomé Garcia: None declared, Sara Ganhão: None declared, Pedro Madureira: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Lúcia Costa: None declared