THU0454 SOMATIC SYMPTOMS IN FIBROMYALGIA AND THEIR CORRELATION WITH DRUG TREATMENT

Background:Drug treatment in fibromyalgia (FM) is often disappointingly ineffective, and there are currently very few data to support therapeutic choices towards a personalized medicine approach.Objectives:To evaluate the prevalence of selected somatic symptoms in FM, and to study their relationship with drug treatments.Methods:The study population consisted of 526 patients (471 F 55 M, mean age 47.31±11.33 yrs) affected by FM not associated with other rheumatic diseases. All patients were required to compile a questionnaire reporting the presence of 42 somatic symptoms -as suggested (1) – in the last 7 days. Drug usage was assessed by interview.Results:On average, patients reported the presence of 17.04±6.68 symptoms (range 4-35), with ample variations in the prevalence of different symptoms (Fig. 1), ranging from over 95% (fatigue and muscle pain) to less than 10 %, seizures being reported by only 2 patients (0.4%). 31.1% of patients were not taking any drug for their FM. The most frequently used drugs were analgesics (ANA, 41.7%) followed by benzodiazepines (BD, 29.1%), SSRIs (16%), gabapentinoids (GABA, 14,4%), and NSRI (14.3%) (Fig. 2). Different drugs were associated with a different spectrum of somatic symptoms: as compared to non users, BD users reported a significantly higher (p< 0.05 by chi-square test) prevalence of irritable bowel (65.4% vs 52.3%), fatigue (98.7% vs 94.9%), thinking difficulties (78.4% vs 68.5%), muscle weakness (94.1% vs 81.7%), abdominal pain (55.6% vs 43.9%), insomnia (73.9% vs 56.6%), depression (63.4 % vs 37.2%), constipation (60.1% vs 42.9%), pain in upper abdomen (50.3% vs 40.2%), nausea (53.6% vs 38.3%), nervousness (71.9% vs 61.5%), chest pain (49.0 vs 37.75), blurred vision (65.4% vs 53.6%), dry mouth (72.5% vs 52.3%), itching (56.2% vs 44.5%), vomiting (13.7% vs 7.8%), taste change (22.2% vs 12.7%), dry eyes (55.6% vs 41.0%), breath shortness (56.9% vs 47.7%), appetite loss (33.3% vs 19.7%), painful urination (15.0% vs 8.4%), and bladder spasms (18.3% vs 8.6%). NRSI users reported a significantly higher prevalence of thinking difficulties, constipation, blurred vision, dry mouth, wheezing, dry eyes, easy bruising. Among GABA users, there was a higher prevalence of thinking difficulties, numbness, insomnia, constipation, nausea, dry mouth, dry eyes, appetite loss, sun sensitivity, easy bruising, and bladder spasms. In no cases a higher prevalence of symptoms was recorded in drug non users vs users.Conclusion:The usage of different drugs in FM is associated with different somatic symptoms. The higher prevalence of symptoms in drug users as compared to non users raises serious questions concerning the opportunity or the appropriateness of drug selection in FM.References:[1]Wolfe F., et al. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10Disclosure of Interests: :None declare

POS0090 RISK OF QT INTERVAL PROLONGATION ASSOCIATED WITH CHRONIC USE OF HYDROXYCHLOROQUINE IN RHEUMATIC PATIENTS AND THE EFFECT OF COTREATMENTS

Background:Hydroxychloroquine (HCQ) has been used safely for over 60 years in rheumatic patients. However, following its recent use in covid-19 disease, its safety has been questioned, following controversial reports of cardiac toxicity1, possibly related to a prolongation of the QT interval2.Objectives:To explore the influence of chronic treatment with hydroxychloroquine on QT interval in rheumatic patients, and the possible effects of drug-to-drug interference3.Methods:12-lead electrocardiogram tracings were recorded with standard equipment in 229 ambulatory patients (SLE = 53, RA = 52, SSc = 56, UCTD = 38, Others = 30). The present analysis was performed on corrected QT intervals (QTc) calculated according to Framingham formula (QTc = QT+0.154 (1−RR)), with ULN = 449 ms in males, and 467 ms in females. Estimated glomerular filtrate rate (eGFR) was calculated from serum creatinine with the CKD-EPI equation. The influence on QTc values of demographic variables, chronic (≥3 months) HCQ treatment, and of the use of selected comedications -Statins, Angiotensin Converting Enzyme inhibitors (ACEi), Angiotensin Receptor Blockers (ARBs), Selective Serotonin Reuptake Inhibitors (SSRIs), Proton-Pump Inhibitors (PPI), Calcium Channel Blockers (CCBs) – were evaluated by parametric or non parametric statistical methods, as appropriate. All statistic al analyses were performed with the IBM SPSS statistical package version 25.Results:Table 1.Demographic and clinical variables in patients treated with HCQ (HCQ+) and in controls (HCQ-).NAgeYrs±SDFemaleN%eGFRmL/min/1.73m2StatinsN%ACEiN%ARBN%SSRIN%PPIN%CCBN%All22958.02±14.3620690.087.1418.962912.74821.8198.3146.113860.33013.1HCQ+13258.71±14.4912292.487.0020.041813.63224.2118.396.88060.61712.9HCQ-9757.51±14.308486.687.3217.471111.31616.588.255.25859.81313.4p0.5320.1830.8970.6900.1891.0000.7821.0001.000Demographic variables, and the use of evaluated comedications were not different in HCQ+ and HCQ- patients (Table 1). In the whole population, the QTc mean duration was 416.72 ± 20.70 ms, and was correlated with age (r = 0.215, p= 0.001), but not with gender (p = 0.548), eGFR (r = -0.93, p = 0.163), or disease (p = 0.092). In only 4 patients (HCQ+: 3 (2.3%) – HCQ-: 1 (1%), p = 0.639) QTc duration was above ULN.QTc duration was not associated with the use of Statins, ACEi, ARBs, or SSRIs (p = 0.454, 0.276, 0.475, and 0.131 respectively), but was significantly prolonged in patients treated with HCQ (421.26 ± 19.19 vs 410.55 ± 21.18 msec, p < 0.001), PPIs (420.57 ± 21.45 vs 410.89 ± 18.12 ms, p < 0.001), and CCBs (424.22 ± 25.97 vs 415.59 ± 19.62 ms, p < 0.033). Furthermore, as reported in Fig. 1, our data show a trend - albeit not statistically significant - towards an additive effect on QT prolongation of the association of PPIs and CCBs with HCQ, even more evident in the case of association of the 3 drug classes.Conclusion:In this study, the QTc interval was significantly prolonged in patients treated with hydroxychloroquine as compared to controls, although significant prolongation was extremely infrequent. Furthermore, our data revealed signs of drug-drug interference, suggesting that regular monitoring of the electrocardiogram is advisable in these patients, often undergoing cotreatment with multiple drugs.References:[1]Imad M. Tleyjeh, et al. The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis. Mayo Clin Proc Innov Qual Outcomes. 2020 Nov 2 doi: 10.1016/j.mayocpiqo.2020.10.005 [Epub ahead of print].[2]Teodoro J. Oscanoa, et al. Frequency of Long QT in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine: A Meta-analysis. Int J Antimicrob Agents.[3]Byung Jin Choi, et al. Risk of QT prolongation through Drug-drug Interactions between Hydroxychloroquine and Concomitant Drugs Prescribed in Real-world Practice. Preprint from Research Square, 22 Sep 2020 DOI: 10.21203/rs.3.rs-79572/v1 PPR: PPR217328.Disclosure of Interests:None declare

POS0230 INTESTINAL MICROBIOTA CHANGES TNF-INHIBITORS INDUCED IN IBD-RELATED SPONDYLOARTHRITIS

Background:the close relationship between joints and gut inflammation has long been known and several data suggest that the dysbiosis could represents the link between Spondyloarthritis (SpA) and Inflammatory Bowel Diseases (IBD). To date, the manipulation of the intestinal microbiota is considered the key to the cure or control of the natural history of several pathologies sustained or favored by dysbiosis. The introduction of biologic drugs, in particular Tumor Necrosis Factor inhibitors (TNFi), revolutionized the management of both these diseases, thanks to the strong inhibition of inflammation and partially indirectly with mechanisms not yet fully clarified. While the impact of conventional drugs on gut microbiota is well known poor data are available about TNFi.Objectives:to investigate the impact of TNFi on gut microbiota.Methods:we included CD or UC patients fulfilling criteria for axial or peripheral SpA (ASAS 2009) on a typical Mediterranean diet, naïve to biologics needing TNFi. Clinical history, physical examination, instrumental examinations, biochemical examination including C-reactive protein (CRP), erhytrocyte sedimentation rate (ESR), HLA-B27 and fecal calprotectin at the baseline and after 6 months were performed. TNFi included infliximab and adalimumab. Fecal samples were collected by patients themselves by 24 hours before the start of the therapy. The processing was performed through metagenomic NGS (next generation sequencing) including the amplification of the V3 and V4 regions of the 16S (V3 and V4) and sequencing on the Illumina MiSeq platform. All patients received the treatment at least until week 24. Clinical disease indices included Visual Analogue Scale (VAS)-pain and Visual Analgue Scale(VAS)-disease activity for all patients, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for axial involvement, clinical disease activity index (CDAI) and Health Assessment Questionnaire-Disability Index (HAQ-DI) for peripheral involvement, Harvey-Bradshaw Index for CD (HBI), or partial Mayo (pMAYO) score for UC, were assessed at baseline and at the end of the study. The study was approved by the ethics committee (approval code 0056924).Results:we evaluated 20 patients affected by enteropatic arthritis, naïve for biologic drugs, treated with TNFi. After six months of therapy we observed a significant increase in Lachnospiracae family (Δ +10.3, p 0.04) and in Coprococcus genus (Δ +2.8, p 0.003). We also observed a decrease trend in Proteobacteria (Δ -8.0 p 0.095) and Gammaproteobacteria (Δ -9, p 0.093) and an increase trend in Clostridia (Δ +8.2 p 0.083). We didn't find differences between TNFi responders (SpA improvement or IBD remission achieved) and not responders in terms of alpha and beta-diversity.Conclusion:the decrease of Proteobacteria and the increase of Lachnospiraceae and Coprococcus is consistent with the hypothesis that TNFi therapy, by decreasing inflammation, tends to restore the intestinal eubiosis. However further studies on larger cohort incuding the evaluation of gut virota and micobiota will be necessary to definitively clarify the effects of TNFi on the composition and function of the gut microbiota.References:[1]Bazin T et al. Sci Rep. 2018;8(1):5446.[2]Aden K et al. Gastroenterology. 2019;157(5):1279-1292.e11.Table 1.Comparison between clinical variables between baseline and T6 (six months)Clinical variablesT0T6P_valueFecal Calprotectin(μg/g)- median (IQR)207.5(125.5-446.2)81(50-197.2)0.004CRP(mg/L)- median(IQR)8.2(4.8-20.8)2.9(1-4)0.001ESR(mm/h)- median(IQR)21.5(10.8-34)11(7.8-21)0.003VAS_pain- median(IQR)50(38.8-60)35(10-42.5)0.001VAS_disease- median(IQR)50(38.8-50)37.5(25-42.5)0.006HAQ- mediana(IQR)0.6(0.1-0.8)0.2(0.1-0.6)0.004BASDAI_score- median(IQR)5.2(4.1-5.6)2.8(2.5-4.3)0.013CDAI_activity- median(IQR)13(10.5-16)7(5.2-11)0.004IBD activity n(%) - 011 (55%)20 (100%)0.174IBD activity n(%) - 16 (30%)0 (0%)IBD activity n(%) - 22 (10%)0 (0%)IBD activity n(%) - 31 (5%)0 (0%)Disclosure of Interests:None declared

Interessamento entesitico in bambini e adolescenti con malattia infiammatoria cronica intestinale: uno studio ecografico

Background: joint involvement is the most common extraintestinal manifestation in paediatric IBD patients. Several studies in adult population have shown that enthesis ultrasound (US) has a high sensitivity in the diagnosis of enthesitis. Objectives: The objective is to evaluate, using a high frequency ultrasound probe, the prevalence of subclinical entheseal involvement in paediatric IBD patients. Methods: 27 paediatric IBD patients [12 Crohn's disease, 13 ulcerative colitis and 2 IBD type unclassified; 15 females and 12 males, mean age of 13,7 years (ranging 7,2-21,0 years)] without clinical signs or symptoms of musculo-skeletal involvement were consecutively investigated with US (ESAOTE MyLAB 70 6-18 MHz linear array transducer) and compared with 24 healthy controls matched for age and sex. Twelve enthesis were scored according to the Madrid Sonographic Enthesis Index (MASEI) in both groups. Results: no patients reached the MASEI score value suggestive for an early spondyloarthritis involvement but the average MASEI score was significantly higher in IBD patients compared to controls (3.15\ub12.84 vs 0.96\ub11.12, p=0.0006).There was also a significantly higher percentage of patients with at least one enthesis with power Doppler (PD) score 652 (37% vs 16%; p= 0.037) and at least one enthesis with dishomogeneous echostructure (59% vs 0%; p= 0.000). No differences were found in terms of erosions, calcifications and structural thickness. In IBD patients, no correlation was found between MASEI total score and sex, age, disease duration and clinical activity scores. Conclusions: US detectable enthesopathy is frequent even in paediatric IBD patients