A Phenome Wide Association Study of Severe COVID-19 Genetic Risk Variants

BackgroundGenetic loci associated with risk of severe COVID-19 infection have been identified and individuals with complicated COVID-19 infections often have multiple comorbidities.ObjectiveIdentify known and unidentified comorbidities associated with genetic loci linked to risk of severe COVID-19 infection.MethodsA Phenome Wide Association Study (PheWAS) was conducted in 247,448 unrelated, white individuals from the UK Biobank to test the association of 1,402 unique phenotypes with ten genome-wide significant severe-COVID risk single nucleotide polymorphisms (SNP) identified from prior studies. A validation PheWAS was conducted in 2,247 white individuals from the CATHGEN.ResultsFour of the ten tested genetic loci showed significant phenotypic associations in UK Biobank after FDR adjustment. Vascular dementia significantly associated with rs7271165 near TMEM65 on 8q24.13 in individuals with the C risk allele (OR 5.66 [95% CI 2.21-11.85], q=0.049). We identified 40 novel phenotype associations with rs657152 on 9q34.2 coinciding with the ABO gene with individuals with the A COVID risk allele having higher odds of heart failure (OR 1.09 [95% CI 1.03-1.14], q=0.004), diabetes mellitus (OR 1.05 [95% CI 1.02-1.07], q=0.004) and hypercholesterolemia (OR 1.04 [95% CI 1.02-1.06], q=6.3×10−5). Eight phenotypes associated with rs1819040 near KANSL1 on 17q21.31 in individuals with the A risk allele including atrial fibrillation and flutter (OR 1.07 [95% CI 1.04-1.10], q=0.0084) and pulmonary fibrosis (OR 0.80 [95% CI 0.71-0.89], q=0.035). Ten novel phenotypic associations were identified in association with rs74956615 on 19p13.2 near the TYK2 gene including individuals with the A COVID risk allele having lower odds of psoriatic arthropathy (OR 0.31 [95% CI 0.20-0.47], q=4.5×10−5), rheumatoid arthritis (OR 0.83 [95% CI 0.64-0.83], p=1.4×10−6) and thyrotoxicosis with or without goiter (OR 0.77 [95% CI 0.68-0.87], p-6.9×10−5). Two associations for rs1819040 (KANSL1) and seven associations for rs74956615 (TYK2) validated in CATHGEN.ConclusionsUsing a broad PheWAS approach in a large discovery and validation cohort, we have identified novel phenotypic associations with risk alleles for severe COVID-19 infection. Interestingly, the ABO locus was associated with comorbidities that are also risk factors for severe COVID-19 infection, suggesting that this locus has pleiotropic effects and provides a potential mechanism for this association. The 19p13 locus was associated with lower risk of autoimmune disease, these findings may have broad implications for the importance of multiple comorbidities across both infectious and non-infectious diseases and may provide insight in the molecular function of the genes near these genetic risk loci.

Experience of therapy of psoriasis patients with methotrexate in the form of subcutaneous and intramuscularly injections

Псориаз является одним из наиболее распространенных хронических дерматозов, в мире зарегистрировано около 125 млн больных этим заболеванием, причем частота встречаемости в структуре дерматологических заболеваний составляет около 40%. Несмотря на то, что в большинстве случаев псориаз не представляет угрозы для жизни, тем не менее он является непосредственной причиной появления весьма серьезных патологических проблем, социальной дезадаптации. В последнее время все большее число исследователей говорят о псориазе не как об изолированном кожном заболевании, а как о системной псориатической болезни с доминирующими проявлениями на коже. Системность заболевания проявляется в частом вовлечении в процесс не только кожного покрова, но и других систем и органов, в частности опорно-двигательного аппарата при артропатической форме псориаза (псориатическом артрите). Распространенность псориатического артрита у больных псориазом колеблется от 7% до 47%, причем у 15% пациентов артрит развивается до поражения кожи, при обычном псориазе артрит бывает в 6-7% случаев, а при уже выявленной псориатической артропатии у 73,2% больных встречается пустулезный или экссудативный псориаз, а также псориатическая эритродермия. В статье представлены результаты применения в терапии больных среднетяжелым и тяжелым псориазом препарата метотрексат в виде подкожных инъекций в сравнении с аналогичной схемой использования внутримышечных инъекций метотрексата. Показана высокая эффективность курса терапии метотрексатом в лечении псориаза и псориатического артрита. Приведены данные о более высокой безопасности, более значимом позитивном влиянии на качество жизни, о лучшей переносимости и более длительной ремиссии, достигнутых в группе пациентов, получавших подкожные инъекции метотрексата. Psoriasis is one of the most common chronic dermatoses. About 125 million patients with this disease are registered in the world, and the frequency of occurrence in the structure of dermatological diseases is about 40%. Despite the fact that in most cases psoriasis does not pose a threat to life, but, nevertheless, it is the direct cause of the appearance of very serious pathological problems, social maladjustment. Recently, an increasing number of researchers speak of psoriasis not as an isolated skin disease, but as a systemic psoriatic disease with dominant skin manifestations. The systemic nature of the disease is manifested in the frequent involvement in the process of not only the skin, but also other systems and organs, in particular, the musculoskeletal system in the arthropathic form of psoriasis (psoriatic arthritis). The prevalence of psoriatic arthritis in patients with psoriasis ranges from 7 to 47%, and in 15% of patients arthritis develops before skin lesions, with ordinary psoriasis, arthritis occurs in 6-7% of cases, and with already identified psoriatic arthropathy in 73,2%, pustular or exudative psoriasis, as well as psoriatic erythroderma. The article presents the results of the use of methotrexate in the form of subcutaneous injections in clinical practice in the treatment of patients with moderate and severe psoriasis, in comparison with a similar scheme of using intramuscular injections of methotrexate. The course of methotrexate therapy has been shown to be highly effective in the treatment of psoriasis and psoriatic arthritis. The data on higher safety, a more significant positive effect on the quality of life, better tolerability and longer remission of the process achieved in a group of patients receiving subcutaneous injections of methotrexate are presented.

Etanercept-Induced Anti-Glomerular Basement Membrane Disease

Anti-glomerular basement membrane (anti-GBM) disease is a rare form of small-vessel vasculitis that typically causes rapidly progressive glomerulonephritis with or without alveolar haemorrhage. Previously, there has only been one reported case of tumour necrosis factor-α (TNF-α) antagonist-induced anti-GBM disease. Here, we describe the first reported case of etanercept-induced anti-GBM disease. A 55-year-old Caucasian man was referred to our tertiary specialist renal centre with a history of painless macroscopic haematuria. The patient has been receiving weekly etanercept injections over the past 12 months for psoriatic arthropathy. The serum immunology panel results highlighted a significantly raised anti-GBM titre (370.1 U). Etanercept was stopped, and the patient was empirically commenced on pulsed methylprednisolone, cyclophosphamide, and plasma exchange. A renal biopsy showed crescentic glomerulonephritis. Few days after admission, he tested positive for coronavirus disease 2019 (COVID-19), and a decision was made to withhold cyclophosphamide. There was further decline in renal function with hyperkalaemia for which he received 2 sessions of haemodialysis. He was restarted on cyclophosphamide upon discharge. The patient was switched to rituximab treatment afterwards as he developed leucopenia 2 weeks following the commencement of cyclophosphamide. The serum creatinine level continued to improve and remained dialysis-independent. In conclusion, with the increased use of etanercept and other TNF-α antagonists, the prescribing clinician must be aware of the rare but life-threatening drug-induced vasculitis. We recommend careful monitoring of renal indices with the use of this class of medications.

Frequency of Different Types of Arthritis in patients of Psoriasis

Background: Psoriatic arthritis (PsA) is type of inflammatory arthritis associated with psoriasis. There are multiple patterns of joint involvement in patients with psoriasis Aim: To determine the frequency of arthritis and its different types in patients of psoriasis presenting at a tertiary care hospital in Lahore Methods: This cross Sectional study was conducted in Dermatology Department of Services Hospital, Lahore from 11th April, 2017 to 10th October, 2017. Two hundred and sixty patients having psoriasis were enrolled in the study, Patients’ detailed history about psoriasis, duration of psoriasis and joint pain or stiffness was taken. After written and informed consent Physical examination was done to determine the type of psoriasis and nail involvement. All the joints were examined for tenderness and deformities to assess the evidence of arthritis and its different types according to the site of involved joints. Results: Total numbers of patients included in the study was 260; in which 176 (67.7%) patients were males and 84 (32.3%) were females with the total mean age of 38 ±13.22 years. Out of 260 patients, 62(23.8%) patients had psoriatic arthritis (PsA), Out of these 62 patients having PsA, 23(37.1%) patients had Oligoarthritis, followed by Symmetric arthritis 19(30.6%) patients, Distal interphalangeal arthritis (DIP) in 15 (24.2 %). Conclusion: Our study concluded that almost one fourth of psoriasis patients had arthritis, asymmetrical oligoarthritis/monoarthritis came out to be the most common type in our study followed by symmetric polyarthritis, distal interphalangeal arthritis (DIP), Arthritis mutilans and axial arthritis Keywords: Psoriasis, types of psoriasis, arthritis, psoriatic arthropathy

POS0287 USE OF BIOLOGIC DISEASE MODIFYING ANTI-RHEUMATIC DRUGS IN RELATION TO THE RISK OF LYMPHOMA: A COHORT STUDY OF US VETERANS WITH RHEUMATOID ARTHRITIS

Background:Epidemiologic studies suggest that disease duration and degree of inflammatory activity of rheumatoid arthritis (RA) contribute to lymphoma development. However, the association of the use of biologic disease modifying anti-rheumatic drugs (bDMARDs) in patients with RA on lymphoma risk needs further evaluation.Objectives:Examine the effect of administration of bDMARDS on the incidence of lymphoma in an inception cohort of RA.Methods:We identified patients diagnosed with RA in any US Veterans Affairs (VA) facility from 1/1/2002 and 12/31/2018 using the Veteran’s Health Administration (VHA) databases. To be included, each patient was required to meet the following criteria: 1) 2+ RA diagnostic codes at least 7 days apart but no more than 365 days apart 2) a prescription for a conventional synthetic DMARD (csDMARD) within 90 days of the first RA diagnosis 3) One inpatient or outpatient visit 30 days to 2 years preceding first RA diagnosis (indicating they are a regular user of the VHA). We excluded patients for any of the following if they preceded the first RA diagnosis: 1) a prior single RA diagnostic code 2) a prescription for any DMARD medication 3) a concomitant diagnosis of another inflammatory arthritis (e.g. psoriatic arthropathy) 4) a diagnosis of lymphoma. Index date for the study is the date of the first qualifying RA diagnosis. Lymphoma diagnoses were identified through VHA records using the International Classification of Diseases-Oncology codes.Results:We identified 27,536 veterans with RA in the study period meeting the inclusion and exclusion criteria. Of these, 53% (n=14,705) were in the age range 60 to 80 years. The cohort was 89% male, 75.5% White, 13.7% African American. Over the study period, 1.2% (n=332) of the study population developed a lymphoma.Conclusion:Using the nationwide VHA we have identified a large inception cohort of patients with RA of whom 1.2% developed lymphoma over study follow-up. This data will be used in future analyses to produce estimates of the effect of biologic medications on lymphoma risk, adjusting for confounding by indication and other variables.Table 1.Baseline characteristics of the cohort based on bDMARD exposure statusCharacteristicbDMARD-naive (n= 19,095)bDMARD-exposed (n=8,441)Overall Lymphomas Age (years)171161 18-4046 40-606378 60-8010074 >8043 Males17,206 (90%)7,270 (86%)Race White14,150 (74%)6,627 (76%) Black2,674 (14%)1,090 (13%) Asian96 (0.5%)46 (0.5%) Native American or Pacific Islander371 (2%)187 (2.2%) Missing1,804 (9%)491 (6%)Acknowledgements:The work in this abstract is supported by Investigator Award from the Rheumatology Research Foundation to Dr Singh.Disclosure of Interests:None declared

Peloids as Thermotherapeutic Agents

The use of peloids as heat-providing therapeutic systems dates back to antiquity. Such systems consist of a liquid phase and an organic or inorganic solid phase. The latter facilitates the handling, preparation and stability of the solid–liquid system, modifying its organoleptic and phy-sicochemical properties, and improves its efficacy and tolerance. Peloids enable the application of heat to very specific zones and the release of heat at a given rate. The aims of this work are to study 16 reference peloids used in medical spa centers as thermo-therapeutic agents as well as to propose nine raw materials as a solid phase for the preparation of peloids. The physical properties studied are the centesimal composition, the instrumental texture and the thermal parameters. In conclusion, the peloids of the medical spas studied are used as thermotherapeutic agents in the treatment of musculoskeletal disorders, especially in knee osteoarthritis and to a lesser extent in back pain and psoriatic arthropathy. The clinical experience in these centers shows that the main effects of the application of their peloids are the reduction of pain, an increase in the joint’s functional capacity and an improvement in the quality of life. As thermotherapeutic agents, all the peloids of the me-dical spas studied and the pastes (raw materials with distilled water) examined showed a heat flow rate of up to four times lower than that shown by the same amount of water. The raw materials studied can be used as solid phases for the preparation of peloids with mineral waters.

OP0073 RISK OF DEVELOPING RHEUMATIC DISEASES IN PATIENTS WITH PALINDROMIC RHEUMATISM IN SOUTH KOREA: A NATION-WIDE POPULATION-BASED STUDY

Background:Palindromic rheumatism (PR) has known to be three patterns of disease course: clinical remission of attacks, persistent attacks, and evolution to chronic arthritis or systemic disease. The spectrum in progression to chronic diseases of PR, however, is quite variable; rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren’s syndrome (SjS), ankylosing spondylitis (AS), relapsing polychondritis (RP), Behçet’s disease (BD), sarcoidosis, and psoriatic spondylitis and arthropathy. Because of the small numbers in case-control studies and too aged investigations, now we needs to shed new light on the fate of PR.Objectives:The aim was to investigate the epidemiology of PR and the risk of developing various rheumatic diseases compared with non-PR individuals, employing the National Health Insurance Service (NHIS) medical claims data, which covers all medical institutions of South Korea.Methods:The study used 2007-2018 claims data from the Korean Health Insurance Review and Assessment Service (HIRA). The identified 19,724 PR patients from 2010 to 2016 were assessed for the incidence rate (IR) compared with the population in the given year by 100,000 person-year (py). The date of diagnosis was the index date. After matching with non-PR individuals (1:10) for age, sex and the year of index date, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs). The risk of developing the various rheumatic diseases and adult immunodeficiency syndrome (AIDS) as the outcome diseases in PR cohort was estimated. This risk was compared with that of matched non-PR cohort.Results:Of 19,724 PR patients (8,665 males and 11,059 females), the mean age was 50.2 ± 14.9 years (47.7 ± 14.4 years in males and 52.6 ± 14.9 years in females,p< 0.001). The ratio of male to female patients with PR was approximately 1:1.28. The annual IR of PR was 7.02 (6.92-7.12) per 100,000 py (6.22 (6.09-6.35) and 7.80 (7.66-7.95) per 100,000 py in males and females, respectively). The mean duration to develop the outcome diseases was significantly shorter in PR cohort compared that of non-PR cohort (19.4 vs. 35.8 months,p< 0.001). The most common outcome disease was RA (7.34% of PR patients; 80.0% of total outcome diseases), followed by AS, SLE, BD, SjS, MCTD, DM/PM, SSc, RP, psoriatic arthropathy, and AIDS in PR cohort. The patients with PR had an increased risk of RA (HR 46.6, 95% CI [41.1-52.7]), psoriatic arthropathy (44.79 [15.2-132.4]), SLE (24.5 [16.2-37.2]), MCTD (22.0 [7.7-63.3]), BD (21.0 [13.8-32.1]), SjS (12.4 [8.5-17.9]), AS (9.0 [6.7-12.2]), DM/PM (6.1 [2.6-14.8]), and SSc (3.8 [1.5-9.6]) but not of AIDS. The risk of developing RA was greater in male patients (HR 58.9, 95% CI [45.6-76.2] vs. 43.2 [37.4-49.8],pfor interaction = 0.037) while female patients encountered a higher risk of developing AS (15.8 [8.9-28.1] vs. 7.2 [5.0-10.3],pfor interaction = 0.023). The risk of developing RA, SLE, SjS, and BD were significantly more highly affected in younger age (pfor interaction < 0.001, = 0.003, 0.002, and 0.017, at each).Conclusion:This nationwide, population-based cohort study demonstrated that patients with PR had an increased risk of developing various rheumatic diseases, not only RA but also psoriatic arthropathy. Therefore, patients with PR needs to be cautiously followed up for their potential of diverse outcome other than RA: RA, SLE, SjS, and BD in younger patients, RA in males, and AS in females, in particular.Disclosure of Interests:None declared

AB0184 ADHERENCE TO TREATMENT IN AN ITALIAN COHORT OF PATIENTS AFFECTED BY CHRONIC INFLAMMATORY ARTHROPATHIES TREATED WITH BIOLOGIC AGENTS

Background:The lack of adherence to treatment in patients affected by chronic diseases, such as rheumatic diseases, remains a relevant issue. Indeed, “inefficacy” or “intolerance” to therapies prescribed could hide a scarce compliance of a considerable percentage of patients.Objectives:We aimed to evaluate the adherence to treatment in a series of patients affected by chronic inflammatory arthropathies treated with biologic agents.Methods:We recruited 175 consecutive patients (M/F: 56/120; mean age 52.6±12.3 years) affected by rheumatoid arthritis (98), psoriatic arthropathy (45) or ankylosing spondylitis (32) treated with subcutaneous biologic agents. All patients completed the Morisky Medication Adherence Scales (MMAS-8)1, in order to estimate their adherence to therapy. Moreover, we achieved from all cases the Patient Global Assessment (PGA), the Visual Analogue Scale (VAS) for articular pain, the Health Assessment Questionnaire (HAQ), and the report of eventual adverse events.Results:Considering MMAS-8, 23/175 (13.1%) patients were low adherent to treatment (score <6), and 59/175 (33.7%) presented medium-grade adherence (score 6-7).Adherence to treatments tended to be higher in males (mean MMAS-8 7.3±1.1 vs. 6.9±1.6; p=0.073), while it was not associated with age, education level, type of articular disease, presence of adverse events, or treatment with the type of traditional or biologic DMARDs.Higher mean levels of PGA (51.3 vs. 38.8; p=0.012), VAS (52.6 vs. 44.3; p=0.08), and HAQ (0.9 vs. 0.5; p=0.001) was reported in low-adherent patients compared with full adherent subjects.Conclusion:Our study confirmed that the percentage of patients showing low adherence to therapy is relevant. Moreover, the association of lower adherence to treatments with higher values of the subjective clinimetric indexes suggests to pay attention to the apparent ineffectiveness or loss of efficacy of therapy.References:[1]Morisky DE et al. J Clin Hypertens 2008; 10:348–354.Disclosure of Interests:None declared