323 Comparison of circulating immune complex and interleukin-6 with standard biomarkers to determine sle disease activity

BackgroundManagement of certain immune mediated adverse events (irAEs) can be challenging and may require prolonged/chronic immune suppression with corticosteroids or other immunosuppressant which could compromise and even reverse the efficacy of immune checkpoint inhibitors (ICI). While the exact immunobiology of irAEs is not fully understood there is enough evidence that IL-6 induced Th-17 that may play critical role in the pathogenesis. Herein, we describe our clinical experience using interleukin-6 receptor (IL-6R) blockade in management of irAEs in melanoma patients.MethodsWe searched MD Anderson databases to identify cancer patients who had received ICIs between January 2004 and March 2020. Of 11,391 ICI-treated patients, 21 patients with melanoma who received IL-6R blockade after ICI infusion were identified and their medical records were reviewed.ResultsMedian age was 61 years (41–82), 52% were females, 90% received anti-programmed cell death-1 antibodies. Fourteen patients (67%) had de novo onset irAEs (11 had arthritis, and 1 each with polymyalgia rheumatica, oral mucositis, and CNS vasculitis), and 7 patients (33%) had flare of their pre-existing autoimmune diseases (5 had had rheumatoid arthritis, and 1 each with myasthenia gravis and Crohn’s disease). Median time from ICI initiation to irAEs was 91 days (range, 1–496) and to initiation of IL-6R blockade was 6.6 months (range, 0.6–24.3). Median number of IL-6R blockade was 12 (range, 1–35), and 16 patients (76%) were concomitantly receiving corticosteroids of median dose of 10 mg (range, 5–20 mg). Of the 21 patients, irAEs improved in 14 (67%) (95% CI: 46%-87%). Of 13 evaluable patients with arthritis, 11 (85%) achieved remission or minimal disease activity as defined by the clinical disease activity index. Median time from initiation of IL-6R blockade till improvement of irAEs was 2.9 months (range, 1.5–36.9). Nineteen patients tolerated well IL-6R blockade, while two patients stopped treatment due to abdominal pain and sinus tachycardia. The median CRP levels at irAEs was 84 mg/L (0.6–187) and decreased to 1.9 mg/L (0.56–12) at 10 weeks after initiation of IL-6R blockade (P=0.02). Of the 17 evaluable patients, the overall tumor response rate by RECIST-1.1 criteria was similar before and after IL-6R blockade initiation (41% vs. 53%).ConclusionsOur data demonstrated that IL-6R blockade could be an effective therapy for irAEs management without dampening the efficacy of ICIs. Prospective clinical trials with longitudinal blood, tumor, and inflamed tissue biopsies are planned to accurately validate these findings and better study the immunobiology of irAEs.Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center intuition’s Ethics Board, approval number PA19-0089

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SAT0111 THE RELATIONSHIP BETWEEN THE ADMINISTRATION OF IL-6 INHIBITORS AND INSULIN RESISTANCE IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6509 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 989.3-989

Author(s):

A. Jitaru ◽

C. Pomirleanu ◽

M. M. Leon-Constantin ◽

F. Mitu ◽

C. Ancuta

Keyword(s):

Rheumatoid Arthritis ◽

Insulin Resistance ◽

Insulin Sensitivity ◽

Beneficial Effect ◽

Disease Activity ◽

Interleukin 6 ◽

Normal Weight ◽

Diabetic Patients ◽

Model Assessment ◽

Inflammatory Status

Background:Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, due not only to the traditional risk factors (hypertension, insulin resistance/diabetes, obesity, smoking), but to the inflammatory status as well. The blockade of interleukin-6 (IL-6) can regulate the glucose metabolism, reducing the glucose level and insulin resistance (IR). This beneficial effect is seen more in patients with normal values of body mass index (BMI), compared to the obese population.Objectives:Given the mentioned existing data, we aim to demonstrate the positive effect of IL-6 inhibitors in active RA patients with normal or increased BMI.Methods:We recruited 56 consecutive patients with definite and active RA, non-responders/partial responders to conventional synthetic Drug Modifying Anti-Rheumatic Drugs (csDMARDs)/biological therapy. For a period of 52 weeks, patients received subcutaneous Tocilizumab (TCZ) in a dose of 162mg once a week, according to European League Anti Rheumatism (EULAR) recommendation and National Protocol. We assessed demographics, RA-related parameters (clinical, inflammatory and immune) and metabolic markers, as well as the peripheral response to insulin, quantified by Homeostasis Model Assessment for insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). We did not include in the study the patients known with diabetes mellitus (DM) and those undergoing glucocorticoids.Results:After 52 weeks of treatment, most of the patients showed a statistically significant reduction of HOMA-IR (3.61 ± 1.21 at the onset vs. 2.45 ± 1.46 at the end of the study, p<0.001), while QUICKI registered a slight increase (0.32 ± 0.01 at the onset vs. 0.33 ± 0.01 at the end of the study, p<0.001). Also, the decrease in insulin and glucose levels were more obvious in patients with normal BMI, strictly related to disease activity.Conclusion:Long-term administration of TCZ in active RA is associated with a significant reduction of disease activity and IR, especially in normal weight patients. This confirms that obesity, as a CV risk factor, represents one of the main causes of IR.References:[1]Castañeda S, Remuzgo-Martínez S, López-Mejías R et al. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis.Clin Exp Rheumatol. 2019; 37(3):465-473.[2]Lehrskov LL, Christensen RH. The role of interleukin-6 in glucose homeostasis and lipid metabolism.Semin Immunopathol. 2019; 41(4):491-499.[3]Ursini F, Russo E, Ruscitti P, Giacomelli R, De Sarro G. The effect of non-TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis.Autoimmun Rev. 2018 Apr;17(4):399-404.Disclosure of Interests:Alexandra Jitaru: None declared, Cristina Pomirleanu: None declared, Maria-Magdalena Leon-Constantin: None declared, Florin Mitu: None declared, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly

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