High Titers Of Rheumatoid Factor Research Articles

Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). Retrospective analysis was conducted on data from the ANSWER cohort comprising 3,623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention. Of these, 450 (12.4%) met the first two criteria of EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared to those under 65, HR = 0.46, 95% CI: 0.31 to 0.69), higher rheumatoid factor (RF) titres (HR = 1.005, 95% CI: 1.00 to 1.01), higher clinical disease activity index (HR = 1.02, 95% CI: 1.01 to 1.03), lower methotrexate dosage (HR = 0.97, 95% CI: 0.95 to 0.99), and comorbidities like hypertension (HR = 1.53, 95% CI: 1.2 to 1.95) and diabetes (HR = 1.37, 95% CI: 1.09 to 1.73). Anti-interleukin 6 receptor antibodies (aIL-6R, HR = 0.53, 95% CI: 0.37 to 0.75) and JAKi (HR = 0.64, 95% CI: 0.46 to 0.90) were associated with fewer discontinuations due to ineffectiveness compared to tumour necrosis factor inhibitors. Oral glucocorticoids usage (HR = 1.65, 95% CI: 1.11 to 2.47) was linked to increased discontinuation due to toxic adverse events. Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.

P106 Do high rheumatoid factor titres impact response to tumour necrosis factor inhibitors? Comparison of certolizumab pegol and adalimumab in patients with rheumatoid arthritis and high titres of rheumatoid factor: a post hoc analysis of a phase 4 trial.

Abstract Background/Aims In patients with rheumatoid arthritis (RA), high rheumatoid factor (RF) titres are considered a poor prognostic factor and are associated with higher disease activity, risk of radiographic progression and decreased response to TNF inhibitors (TNFis). Recent data suggests that patients with RA and high RF titre may achieve and maintain greater clinical improvement with TNFis without a crystallisable fragment (Fc) compared to TNFis with an Fc. In this analysis of the EXXELERATE trial, we assessed efficacy outcomes of certolizumab pegol (CZP), a PEGylated Fc-free TNFi, versus adalimumab (ADA; Fc-containing TNFi) in patients with RA and high RF titres. Methods The phase 4 EXXELERATE trial (NCT01500278) compared the efficacy and safety of CZP to ADA. Patients were randomised 1:1 to CZP 200 mg every two weeks (Q2W) plus methotrexate (MTX) or ADA 40 mg Q2W plus MTX. At Week 12 (Wk), patients were classified as responders or non-responders; non-responders were switched to the other TNFi with possible follow-up to Wk104. Here, we report drug plasma concentrations, mean disease activity score (DAS)28-CRP score and proportion of patients achieving low disease activity (LDA; threshold: DAS28-CRP ≤2.7) to Wk104. Results are stratified by RF titre quartile (≤Q3: ≤203 IU/mL; >Q3: >203 IU/mL; measured by Roche Tina-quant®) and reported as observed data. Results Baseline data by RF quartile were available for 453 CZP-randomised patients (≤Q3: n = 334; >Q3: n = 119) and 454 ADA-randomised patients (≤Q3: n = 347; >Q3 n = 107). Baseline characteristics were similar between CZP- and ADA-randomised patients across the RF titre quartiles. At Wk12, 66 CZP-treated patients switched to ADA and 59 ADA-treated patients switched to CZP. At Wk104, mean ADA concentrations were 22.9% lower in patients with RF >Q3 (mean [SD] 4.8 [3.0]) vs those with RF ≤Q3 (6.2 [4.0]); in CZP-treated patients, this difference was smaller (13.0%) in patients with RF >Q3 (23.3 [15.4]) vs those with RF ≤Q3 (26.7 [13.1]). For patients in RF ≤Q3, mean DAS28-CRP scores were similar between CZP- and ADA-treated patients through Wks0-104 (mean [SD] DAS28 at Wk104: 2.48 [1.18] CZP vs 2.49 [1.14] ADA). However, for patients in RF >Q3, mean [SD] DAS28-CRP scores were nominally lower in CZP- vs ADA-treated patients (Wk104: 2.50 [1.18] CZP vs 2.93 [1.22] ADA). A similar pattern was observed for the proportion of patients achieving LDA at Wk104 (≤Q3: 64.8% CZP vs 65.1% ADA; >Q3: 65.7% CZP vs 48.3% ADA). Conclusion CZP-treated patients with RA and high titre RF had similar drug concentrations and clinical responses to patients with RA and low titre RF, a pattern not observed in ADA-treated patients. These data, together with previous reports where CZP showed consistent efficacy irrespective of baseline RF titre, suggest CZP may be a suitable therapy for patients with RA and high RF titre. Disclosure J.S. Smolen: Honoraria; AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, R-Pharma, Roche, Samsung, Sanofi, and UCB Pharma. Grants/research support; AbbVie, AstraZeneca, Eli Lilly, Novartis and Roche. Other; Editor of Annals of the Rheumatic Diseases, Co-editor of Rheumatology 7E/8E, Convenor of EULAR Task Forces and T2T Task Forces. P.C. Taylor: Consultancies; AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead, GSK, Janssen, Nordic Pharma, Pfizer, Sanofi and UCB Pharma. Grants/research support; Galapagos. Y. Tanaka: Honoraria; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho, Taisho. Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho and Taisho. Grants/research support; Chugai, Eisai, Mitsubishi-Tanabe, Taisho. C. Cara: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. B. Lauwerys: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. R. Xavier: Consultancies; AbbVie, AstraZeneca, Janssen, Organon, UCB Pharma. Member of speakers’ bureau; AbbVie, AstraZeneca, Janssen, Organon, and UCB Pharma. J.R. Curtis: Consultancies; AbbVie, Amgen, BMS, Corrona, Crescendo, Genentech, Janssen, Pfizer, Roche, UCB Pharma. Grants/research support; AbbVie, Amgen, BMS, Corrona, Crescendo, Genentech, Janssen, Pfizer, Roche, UCB Pharma. T.R. Mikuls: Consultancies; Horizon Therapeutics, Pfizer, Sanofi, UCB Pharma. Royalties; Elsevier, Wolters Kluwer Health (UpToDate). Grants/research support; Horizon Therapeutics. M. Weinblatt: Consultancies; AbbVie, Aclaris, Amgen, Aqtual, BMS, CorEvitas, Eli Lilly, GSK, Gilead, Horizon, Johnson and Johnson, Prometheus, Pfizer, Rani, Revolo, Sanofi, Scipher, Sci Rhom, Set Point, UCB Pharma. Grants/research support; AbbVie, Aqtual, BMS, Janssen.

JACCOUD’S ARTHROPATHY IN SYSTEMIC LUPUS ERYTHEMATOSIS: A CASE REPORT

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical signs and symptoms. Musculoskeletal problems (e.g. arthralgia, inflammatory arthritis, and non-erosive arthritis) are the first symptom in roughly 80% of individuals. Jaccoud’s arthropathy, which is regarded as reversible, non-erosive, and deforming arthropathy, can be observed in patients with systemic lupus erythematosus in relation to tenosynovitis, capsule retraction, ligament laxity, and muscular imbalance. Risk factors include longer disease duration, higher titers of rheumatoid factor, and anti–double stranded deoxyribonucleic acid (anti-dsDNA) antibody positivity. In the current article, a case with SLE and associated Jaccoud’s arthropathy was presented.

A case report of pre-eclampsia-like endothelial injury in the kidney of an 85-year-old man treated with ibrutinib

BackgroundGlomerular endotheliosis is the pathognomonic glomerular lesion in pre-eclampsia that has also been described in those taking tyrosine kinase inhibitors for cancer treatment. Ibrutinib is a Bruton’s tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). We report the first known case of glomerular endotheliosis on kidney biopsy in a patient on ibrutinib monotherapy.Case presentationThe patient presented with acute on chronic kidney disease, proteinuria, low C3 and C4 and a high rheumatoid factor titer. A kidney biopsy was performed to confirm a preliminary diagnosis of membranoproliferative glomerulonephritis (MPGN), the most common glomerular disease in patients with CLL. Unexpectedly, the kidney biopsy showed pre-eclampsia-like lesions on light and electron microscopy: occlusion of glomerular peripheral capillary lumens by swollen reactive endothelial cells. Findings of glomerulonephritis were not seen, and there were no specific glomerular immune deposits by immunofluorescence or electron microscopy.ConclusionsCLL is known to cause glomerular lesions, mainly MPGN. There is increasing evidence that ibrutinib, a major treatment for CLL, can cause kidney disease, but the precise pathology is not characterized. We present a patient with CLL on ibrutinib with signs of glomerular endotheliosis. Based on the absence of CLL-induced kidney pathologies typically seen on the kidney biopsy and the non-selectivity of ibrutinib, we attributed the glomerular endotheliosis to ibrutinib. In pre-eclampsia, increased soluble fms-like tyrosine kinase 1 (sFlt1) levels induce endothelial dysfunction by decreasing vascular endothelial growth factor (VEGF). Ibrutinib has been demonstrated to have non-selective tyrosine kinase inhibition, including inhibition of VEGF receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR and EGFR inhibitors have recently been described in the literature to cause hypertension, proteinuria, and glomerular endotheliosis. Kidney biopsy should be performed in CLL patients on ibrutinib that present with acute kidney injury (AKI) or proteinuria to determine whether the clinical picture is attributable to the disease itself or a complication of the therapy.

Osteoprotegerin and MTHFR gene variations in rheumatoid arthritis: association with disease susceptibility and markers of subclinical atherosclerosis

We aimed to explore whether the rs2073618 variant (G1181C) of the osteoprotegerin (OPG) gene and the methylenetetrahydrofolate reductase (MTHFR) rs1801131 (A1298AC) and rs1801133 (C677T) gene polymorphisms contribute to rheumatoid arthritis (RA) susceptibility and RA related subclinical atherosclerosis. Overall 283 RA patients and 595 healthy controls (HC) were genotyped for common variants of the OPG and MTHFR genes using PCR based assays. Clinical and laboratory parameters were recorded following thorough chart review. Surrogate markers of subclinical atherosclerosis (Carotid/Femoral intima media thickness/plaque formation) along with traditional risk factors for atherosclerosis were assessed in all RA patients and 280HC. Increased prevalence of the CC genotype of the rs2073618 variant was detected in RA patients vs HC (42.4% vs. 33%, p-value: 0.04). RA patients with high serum titers of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibodies displayed increased prevalence of the CC genotype of the rs2073618 variant of the OPG gene compared to HC (48.6% and 47.5 vs 33.3%, p-values: 0.0029and 0.0077 respectively). Of interest, this genotype turned to be associated with higher carotid IMT scores (0.872 ± 0.264 vs 0.816 ± 0.284, p-value: 0.01) and marginally with higher rates of carotid plaque formation (66% vs 54.1%, p = 0.06). The MTHFR 1298CC genotype was more prevalent only in the anti-CCP positive group compared to HC, with no associations detected with markers of subclinical atherosclerosis, following adjustment for traditional cardiovascular (CVD) risk factors. Reduced rates of carotid/femoral plaque formation were detected among RA patients harboring the MTHFR TT genotype (52.4 vs 72.7, p-value: 0.009, respectively). This association remained significant following adjustment for classical CVD risk factors (OR [95% CI 0.364 [0.173–0.765], p-value: 0.008). Genetic variations of the osteoprotegerin and MTHFR genes seem to increase susceptibility for seropositive RA and potentially contribute to subclinical atherosclerosis linked to RA. Larger studies are needed to confirm these findings.

POS0647 DOES TNF INHIBITOR MOLECULAR STRUCTURE MATTER? ANALYSIS OF IMPACT OF BASELINE RHEUMATOID FACTOR TITERS ON DRUG LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS

BackgroundElevated rheumatoid factor (RF) in patients with rheumatoid arthritis (RA) is associated with higher disease activity and increased risk for disease progression1.Recent publications indicate significantly lower efficacy of TNF inhibitors (TNFi) in RA patients with high RF levels compared with low/negative RF subgroup2,3. Fab therapy with Certolizumab pegol (CZP), a PEGylated, Fc-free monoclonal antibody (mAb), has shown comparable efficacy and consistent serum levels irrespective of baseline RF4.RF binds the Fc region of IgG1, the subtype used to engineer the majority of mAbs5. Formation of large immune complexes may likely explain the inceased clearance of mAbs in patients with high RF titers and reported reduced TNFi efficacy.ObjectivesWe aimed to evaluate in clinical practice whether RF levels in RA patients influence serum drug levels of 3 TNFi with different molecular structures.MethodsWe evaluated retrospectively a cohort of RA patients from La Paz University Hospital (RA-Paz Registry, 1999-2019) treated with Infliximab (IFX), Adalimumab (ADA) or CZP. Clinical and demographic data were collected at baseline (T0) and after 6 months (T6) of treatment. RF titers and serum drug levels were measured at T0 and T6 using nephelometry and ELISA respectively. Association between baseline RF titers and drug levels was assessed using non-parametric test (Mann-Whitney).Results168 patients were evaluated: 90 received IFX, 48 ADA and 32 CZP. Characteristics at T0 are shown in Table 1. All patients had active disease at baseline and 76% were RF positive: ADA subgroup had lower percentage of positive RF than IFX and CZP subgroups. Patients were stratified into quartiles based on baseline RF titers: low (20-57 IU/ml), medium (57-380 IU/ml), high (>380 IU/ml) and seronegative (<20 IU/ml).Table 1.Baseline characteristics.CharacteristicsTotal (n=168)IFX (n=90)ADL (n=48)CZP (n=32)p valueAge, years*55.5(45.3-66)57(46-65)50(42-64)61(47-70)0.08Body mass index, Kg/m2*24.5(21.7-29)24.2(21.8-27.7)24.7(21.5-30.3)24.6(22.2-30.3)0.3Male, n(%)28(17%)14(15%)9(19%)5(17%)0.2Disease duration, years*8.7(4.5-14.3)8.4 (4.4-14.3)8.8 (3.9-16)9.7(5-12)0.06Smoking status, n(%)0.03Currently/ex-smoker66(39%)29(32%)22(48%)16(57%)Non-smoker96(57%)61(68%)24(52%)12(43%)RF, n(%)128(76%)75(83%)28(58%)25(81%)0.002ACPA, n(%)134(80%)73(81%)35(73%)27(84%)0.3DAS28**5.1(1.3)5.4(1.3)4.5(1.3)4.9(1.3)0.002CRP levels*7.8(3-21.8)10.3(3.2-25.2)5.1(1.4-10.1)7.8(2.3-18.2)0.1Prior bDMARDs, n(%)26(15%)10 (11%)10 (21%)6(20%)0.2Monotherapy, n(%)16(10%)8(9%)8(17%)00.2csDMARDS, n(%)152(90%)82(91%)82(91%)32(100%)Methotrexate, n(%)112(67%)64(78%)33(83%)17(53%)0.2Other csDMARDs, n(%)24(24%)18(22%)7(18%)15(50%)0.0008Prednisone, n(%)85(51%)49(54%)21(44%)16(50%)0.6*Median and interquartile range;**mean and standard deviationDrug levels of IFX and ADA at T6 were significantly lower in those patients who had higher RF titers at T0 compared to seronegative. In contrast, CZP levels remained stable irrespectively of baseline RF titers, without significant differences among quartiles (Figure 1).ConclusionHigher baseline RF titers are associated with lower IFX and ADA levels at T6 in a cohort of RA patients. A concentration-response association has been clearly established for TNFi, and baseline RF levels appear to influence drug levels.Reduced immune complexes formation with CZP may result in a limited impact of baseline RF titers on drug levels.

Disease characteristics in high versus low titers of rheumatoid factor or anti-citrullinated peptide antibody in rheumatoid arthritis patients

Aim of the workTo evaluate the impact of the level of rheumatoid factor (RF) or anti-citrullinated peptide antibody (ACPA) positivity on the clinical manifestations, disease activity, functional status, and treatment strategy among rheumatoid arthritis (RA) patients. Patients and methodsIn this study, 120 consecutive RA patients were grouped according to the level of RF or ACPA positivity. Group 1: patients with low positive RF or ACPA and Group 2: those with high titer. Disease activity score (DAS28) and functional status using modified health assessment questionnaire (MHAQ) were assessed ResultsThe patients mean age was 46.9 ± 10.9 years and female to male ratio was 7:1. 44 (36.7%) patients had low positive RF/ACPA titers, 59 (49.2%) had high titers and 17 (14.2%) had negative RF/ACPA and were excluded. Patients' global assessment of disease activity was significantly higher among patients with high RF/ACPA titer compared to those with low titer (p = 0.04) and MHAQ tended to be higher (p = 0.058). Subcutaneous nodules (p = 0.037) were more frequent among those with high RF/ACPA titer. The cumulative (p = 0.012) and the current (p = 0.006) steroid doses administered both turned out to be significantly higher in the high positive RF/ACPA patient group. ConclusionPatients with high titer RF and\\or ACPA have factors that may contribute to poor outcome as the presence of reduced functional status which indicated by the higher MHAQ score, the need for higher daily and cumulative steroid doses as an indirect indicator of increased disease activity and in turn poor outcome.

The new onset seropositive rheumatoid arthritis after COVID-19 infection: coincidental or related

Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The relationship of COVID-19 with rheumatological disorders has been researched since 2019. Rheumatoid arthritis (RA) is one of the most common rheumatoid diseases. The relationship between RA and COVID-19 is particularly interesting due to common cytokines in etiopathogenesis. SARS-CoV-2 was involved in triggering RF-positive and ACPA-positive arthritis, which might be diagnosed as rheumatoid arthritis, but we cannot rule out the possibility that the onset of this arthritis could have been coincidental. We report the case who has the first flare of RA with a high titer of Rheumatoid Factor (RF) and Anti Citrullinated Protein Antibody (ACPA) after mild SARS-CoV- 2 infection.

Differential efficacy of TNF inhibitors with or without the immunoglobulin fragment crystallizable (Fc) portion in rheumatoid arthritis: the ANSWER cohort study.

Rheumatoid factor (RF) binds to the fragment crystallizable (Fc) portion of immunoglobulin. It could bind to the Fc portion of anti-TNF inhibitors (TNFi) and attenuate the clinical efficacy. We tried to determine whether the therapeutic efficacy of TNFi with Fc might be lower than that of TNFi without Fc in rheumatoid arthritis (RA) patients with high titres of RF. The Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational multi-center registry of patients with RA in the Kansai district of Japan. RA patients treated with TNFi were included and divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, and etanercept) and TNFi without Fc (certolizumab pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was compared by Mann-Whitney U test between TNFi with and without Fc in each RF titre group. Multiple linear regression analysis was used to analyze the effect of TNFi without Fc for the change of DAS28-ESR adjusted after potential confounders. A total of 705 RA patients were classified into four groups (RF1; RF 0-15.0IU/mL, RF2; 15.0-55.0, RF3; 55.0-166, RF4; 166-7555). In RF4, RA patients treated with TNFi without Fc had a significantly lower DAS28-ESR than those treated with TNFi with Fc [3.2 (2.3-4.2) vs. 2.7 (2.0-3.0)] after 12months. This effect of TNFi without Fc for the change of DAS28-ESR after 12months treatment retained in multivariate analysis in RF4. TNFi without Fc may be more efficacious than TNFi with Fc in RA patients with high RF titres.

Amidst the chaos of late rheumatoid arthritis with no treatment

A 78-year-old man with 24 years history of Rheumatoid Arthritis (RA) came with neck pain. He always refused any treatment except for NSAIDs. From 2 years ago, he was bedridden. He was chronic cigarette smoker. On examination, he had rheumatoid nodules, severe both hands deformity, elbows flexion contracture and knee joints limitation of motion. His lab tests showed high titer of rheumatoid factor and anti cyclic citrullinated protein antibody, high ESR, CRP and vitamin D deficiency. Radiologic studies showed multiple vertebral osteoporotic fractures. Cervical spine CT scan (a and b) showed destruction of the odontoid process and fusion of facet joints of the C2, C3 and C4. MRI of cervical spine (c) showed destruction of odontoid process surrounding by inflammatory synovitis. CT scan of lung (e and f) showed multiple upper lobeand sub pleural nodules along fibrotic changes in base of right lobe. X-ray of knee and hip (d and g) showed severe osteoarthritis andsite of previouship nailing. The patient was diagnosed with advanced erosive nodular RA, severe secondary osteoporosis, osteoarthritis and rheumatoid lung. Standard treatment was recommended, although he again refused. RA can result in progressive joint destruction, deformity and disability [1]. In the spine, it has a predilection for the cervical area, leads to odontoid erosion, spinal instability, and subluxation. In the era of importance of early treatment, these complications are rarely seen, however despite biologic therapy, it has been shown that 15-30% of RA patients can still have preclinical cervical spine abnormalities [2]. The Osteoporosis (OP) is more frequent in patients with high disease activity, bone erosions, >10 years disease duration, and high titers of anti-CCP and RF positivity [3]. Our patient with multiple poor prognostic factors for erosive RA came with extra articular and complications of this disease due refusing treatment.

Lymphoid Interstitial Pneumonitis In Rheumatoid Arthritis

Lymphoid Interstitial Pneumonitis (LIP) is a rare interstitial lung disease in rheumatoid arthritis (RA). LIP occurs in a patient with high titers of rheumatoid factor (RF), absence of inflammatory pain and limited joint damage, despite long-standing RA. In these patients, extra-articular manifestations occur even if joint disease activity is low. RA is an autoimmune disease which affects mostly the diarthrodial joints but can also have extra-articular manifestations such as lung disease. Interstitial lung disease (ILD) is frequently encountered in patients with RA. Patterns of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), lymphoid interstitial pneumonitis (LIP) and organizing pneumonia (OP) have been described on surgical lung biopsies in RA patients [1].

High-titer rheumatoid factor seropositivity predicts mediastinal lymphadenopathy and mortality in rheumatoid arthritis-related interstitial lung disease

Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is a common connective tissue disease-related ILD (CTD-ILD) associated with high morbidity and mortality. Although rheumatoid factor (RF) seropositivity is a risk factor for developing RA-ILD, the relationship between RF seropositivity, mediastinal lymph node (MLN) features, and disease progression is unknown. We aimed to determine if high-titer RF seropositivity predicted MLN features, lung function impairment, and mortality in RA-ILD. In this retrospective cohort study, we identified patients in the University of Chicago ILD registry with RA-ILD. We compared demographic characteristics, serologic data, MLN size, count and location, and pulmonary function over 36 months among patients who had high-titer RF seropositivity (≥ 60 IU/ml) and those who did not. Survival analysis was performed using Cox regression modeling. Amongst 294 patients with CTD-ILD, available chest computed tomography (CT) imaging and serologic data, we identified 70 patients with RA-ILD. Compared to RA-ILD patients with low-titer RF, RA-ILD patients with high-titer RF had lower baseline forced vital capacity (71% vs. 63%; P = 0.045), elevated anti-cyclic citrullinated peptide titer (122 vs. 201; P = 0.001), CT honeycombing (50% vs. 80%; P = 0.008), and higher number of MLN ≥ 10 mm (36% vs. 76%; P = 0.005). Lung function decline over 36 months did not differ between groups. Primary outcomes of death or lung transplant occurred more frequently in the high-titer RF group (HR 2.8; 95% CI 1.1–6.8; P = 0.028). High-titer RF seropositivity was associated with MLN enlargement, CT honeycombing, and decreased transplant-free survival. RF titer may be a useful prognostic marker for stratifying patients by pulmonary disease activity and mortality risk.

Incident Rheumatoid Arthritis in HIV Infection: Epidemiology and Treatment.

To assess the incidence, presentation, and management of rheumatoid arthritis (RA) in patients with HIV, including the use of disease-modifying antirheumatic drugs (DMARDs) in this immunosuppressed population. Patients included in this study were from the Veterans Aging Cohort Study, a longitudinal cohort of veterans with HIV and age-, race-, and site-matched uninfected veterans. We identified all patients who had ≥1 rheumatologist-generated International Classification of Diseases, Ninth Revision (ICD-9) or Tenth Revision (ICD-10) code for RA and whose serum samples were tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. To further confirm the diagnosis of RA, medical charts were reviewed to verify whether patients met the American College of Rheumatology/European Alliance of Associations for Rheumatology 2010 criteria for RA. We recorded DMARD use and adverse effects during the first contiguous course of treatment (i.e., >6 months of no interruption in DMARD treatment). This study included 56,250 patients with HIV and 116,944 uninfected individuals over 2,384,541 person-years. Of the 2,748 individuals in this cohort who were reviewed for a diagnosis of RA based on ICD-9 or ICD-10 codes, incident RA was identified in 215 individuals, including 21 patients with HIV. The incidence rate ratio of RA for patients with HIV compared to uninfected individuals was 0.29 (95% confidence interval 0.19-0.48). Most of the patients diagnosed as having RA(88%) were seropositivefor RA-associated autoantibodies (RF and/or anti-CCP). However, high autoantibody titers were less frequent in RA patients with HIV compared to RA patients without HIV. In total, 5% of RA patients with HIV (1 of 21) had both high titers of anti-CCP and high titers of RF, compared to 41% of uninfected individuals (81 of 194). DMARDs were prescribed in 71% of RA patients with HIV (15 of 21) compared to 94% of RA patients without HIV (183 of 194). There was no indication that the DMARD safety profile was worse among RA patients with HIV who were prescribed DMARDs (n = 10 assessed) compared to RA patients without HIV who were prescribed DMARDs (n = 158 assessed). In this cohort, incident RA was less common in patients with HIV compared to uninfected individuals. Moreover, compared to RA patients without HIV, the seropositivity rate and titers of RA-specific autoantibodies were lower among RA patients with HIV, and those with HIV were prescribed DMARDs less frequently than those without HIV.

Bone Loss and Radiographic Damage Profile in Rheumatoid Arthritis Moroccan Patients.

BackgroundRheumatoid arthritis (RA) is a known cause of joint destruction and systemic bone loss. In this study, we aimed to evaluate the bone damage and bone loss profiles of established RA patients.MethodsWe designed a cross-sectional study on a cohort of established RA patients. The bone evaluation was performed by obtaining standard X-ray images of hands and feet combined with bone mineral density (BMD) measurements. Radiographic joint damage was calculated by the modified total Sharp /van der Heijde score (mTSS). BMD was obtained by performing dual energy X-ray absorptiometry of the lumbar spine and femoral neck. Data on age, smoking, alcoholism, steroid prescription, body mass index (BMI), disease duration, disease activity, and functional disability were collected.ResultsA total of 93 RA patients were recruited. Their mean age was 51.59±12.38 years, with a mean disease duration of 12.07±9.19 years. A total of 36.6% of patients had osteoporosis, and the mean mTSS was 70.33±48.93. Both hip (P=0.0005) and lumbar BMD (P=0.0005) were correlated with mTSS. Backward regression analyses determined that bone damage was associated with high titers of rheumatoid factor, low lumbar BMD, and low BMI. General bone loss was associated with gender, steroid dose, steroid duration, menopause, and BMI.ConclusionsBone damage was associated with low BMI and axial bone loss in our RA population.

Beyond the joints, the extra-articular manifestations in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease typically affecting the joints, but the systemic inflammatory process may involve other tissues and organs. Many extra-articular manifestations are recognized, which are related to worse long outcomes. Rheumatoid nodules are the most common extra-articular feature, found in about 30% of patients. Secondary Sjögren's syndrome and pulmonary manifestations are observed in almost 10% of patients, also in the early disease. Active RA with high disease activity has been associated with an increased risk of such features. Male gender, smoking habit, severe joint disease, worse function, high pro-inflammatory markers levels, high titer of rheumatoid factor, and HLA-related shared epitope have been reported as clinical predictors of occurrence of these rheumatoid complications. In addition, there is a little evidence deriving from randomized controlled trials in this field, thus the therapeutic strategy is mainly empiric and based on small case series and retrospective studies. However, considering that these extra-articular manifestations are usually related to the more active and severe RA, an aggressive therapeutic strategy is usually employed in view of the poor outcomes of these patients. The extra-articular features of RA remain, despite the improvement of joint damage, a major diagnostic and therapeutic challenge, since these are associated with a poor prognosis and need to be early recognized and promptly managed.

AB0552 CHARACTERISTICS OF MYOSITIS SPECTRUM DISEASE - RHEUMATOID ARTHRITIS OVERLAP CASES IN A HUNGARIAN COHORT

Background:Overlap syndromes are autoimmune disorders in which classification criteria of at least two connective tissue diseases (CTDs) are fulfilled. The Division of Clinical Immunology in Debrecen, Hungary oversees patients with idiopathic inflammatory myopathies (IIMs) since the 1980’s.Objectives:In a work called The Myositis Antibody Research Project, which is coordinated together with the Bath Institute for Rheumatic Diseases (UK), authors investigated 330 patients with myositis, all treated in this Hungarian center.Methods:The aim of this retrospective study was to investigate the frequency, clinical and serological parameters and therapeutic options in myositis – rheumatoid arthritis overlap cases in this group of 330 patients.Results:The frequency of overlap cases, as seen in literature, was 13.64%. The importance of myositis-associated antibodies (MAAs) can be seen on this results: 44.44% of overlap patients, while only 7.02% of not overlap patients were MAA positive. Out of our 45 overlap patients twenty-seven myositis - RA overlap patients could be identified. Among these 27 patients the women:men ratio was 12.5:1, PM:DM ratio was 2.375:1. Muscle weakness and sceletal involvement was present in every patient, myalgia in 77.78% and Raynaud’s phenomenon in 48.15% of the patients; general symptoms during disease relapse (fatigue, weight loss, fever) were present in 59.26%, 18.52% and 14.82%, respectively. Ten cases had seropositive rheumatoid arthritis, with high titer of rheumatoid factor. Authors underline the importance of lung involvement as internal organ manifestation: 8 patients had anti-synthetase antibodies (six anti-Jo-1, one anti-PL-7 and one anti-PL-12). In anti-PL-7 and anti-PL-12 positive patients interstitial lung disease (ILD) appeared some years before myositis and early agressive management of ILD resulted in fast remission of muscle weakness. Anti-Mi-2 and anti-SRP could be detected in two patients. Most frequent used disease modifying antirheumatic drugs were cyclophosphamide, methotrexate and cyclosporine, 19 patients received DMARD combination therapy. Biological therapy was used in 3 patients, intravenous or subcutaneous immuneglobulin in 4 patients and one patient with RA – myositis – antiphospholipid syndrome died because of asipartion pneumonia.Conclusion:Authors conclude that it is really challenging to treat these overlap cases: they form a very heterogenous group of patients and management has to be personalized.Disclosure of Interests:None declared

Phenotypic variability in a child with Felty\u2019s syndrome: a case report

BackgroundFelty’s syndrome (FS) is characterized by the triad of rheumatoid arthritis (RA), splenomegaly and neutropenia. The arthritis is typically severe and virtually always associated with high-titer rheumatoid factor. The presence of persistent neutropenia is generally required to make the diagnosis. Most patients diagnosed with FS are aged 50–70 years and have had RA for more than 10 years. It is rarely seen in patients with juvenile idiopathic arthritis (JIA), with only five cases having been reported throughout the world.Case presentationThe present study describes the case of a 14-year-old female with a seven-year history of polyarticular JIA, presenting with splenomegaly, hepatomegaly, cholestasis and thrombocytopenia. However, she occasionally developed neutropenia. Titers of rheumatoid factor and anti-CCP were persistently high, and the antinuclear antibody titer was 1:320, while the antibody results for anti-dsDNA and anti-Sm were negative. Serum levels of IgA, IgG, IgM and IgE were all persistently elevated, and the ratio of CD19+ lymphocytes in the subgroups of lymphocytes was persistently high. The level of complements was normal. No STAT3 and STAT5B mutations were found by next-generation sequencing. The patient did not respond to methotrexate, prednisolone, hydroxychloroquine (HCQ), sulfasalazine and etanercept but was responsive to rituximab.ConclusionsJIA, thrombocytopenia and splenomegaly are the most common and important features in six children with FS, while persistent neutropenia is not seen in all these patients. No complement deficiency has been found in children with FS so far. Manifestations of FS without neutropenia may be extremely rare. There are differences between adults and children in the clinical and laboratory features of FS.

Report of a Homeopathic Medication Regimen Containing Artemether/Lumefantrine in a Patient With Rheumatoid Arthritis.

Report of a Homeopathic Medication Regimen Containing Artemether/Lumefantrine in a Patient With Rheumatoid Arthritis.

Factors Associated with Extra Articular Manifestations in Rheumatoid Arthritis

Introduction: Rheumatoid arthritis is a chronic, systemic and inflammatory joint disease that primarily affects the joints and can be associated with a variety of extra-articular manifestations. The aim of this study is to determine the frequency and the factors associated with those extra-articular manifestations.Materials and methods: Cross-sectional study of hospitalized cases of rheumatoid arthritis in our department between January 2012 and January 2018. We studied the prevalence of the extra-articular manifestations and associated factors. The analysis was done by the software EPI INFO 3.5.4.Results : 294 cases of rheumatoid arthritis included. The average age was 53.2 years +/- 12.3 with female predominance F / M = 6.1. The diagnosis lag time was 10.7 +/- 6.9 years. Half of our patients (50.7%) had systemic manifestations. In order of frequency, we distinguish: Osteoporosis (39.6%), Sjögren's syndrome (22.1%), pulmonary involvement (16.1%), dermatological manifestations (8.8%), cardiac involvement (8.8%), ocular involvement (3.1%) carpal tunnel syndrom (1.3%) and vasculitis (1.3%). The extra-articular manifestations were associated with several factors on bivariate analysis : advanced age (p = 0.014), longer duration of disease (p = 0.006), deformities (p = 0.000), seropositivity (p = 0.02), high titers of rheumatoid factor (p = 0.03), destruction (p = 0.02), bone erosions (p = 0.012) and non-use of biotherapy (p = 0.04). Factors whose association was statistically significant, after multivariate logistic regression analysis, were: advanced age (p = 0.04, OR = 1.02 [1.001-1.043], and longer duration of disease (p = 0.02 OR = 1.04 [1.005-1.082]).Conclusion: In our Moroccan context, half of the patients with rheumatoid arthritis had extra-articular manifestations. Older patients with longer disease evolution are the most involved.

Rheumatoid Arthritis-Associated Interstitial Lung Disease: Clinical Characteristics and Predictors of Mortality

Introduction: Interstitial lung disease (ILD) is a serious extraarticular manifestation of rheumatoid arthritis (RA), but no evidence-based therapy exists. Ongoing studies investigate the role of antifibrotic therapies for progressive fibrosing ILD (PF-ILD), including RA-ILD. The aim of the present study was to investigate the frequency of PF-ILD and the clinical characteristics of RA-ILD in a well-characterised, population-based cohort. Methods: We identified patients with RA-ILD diagnosed and followed at the ILD referral centre in Aarhus, Denmark, from 2004 to 2016. Adjusted hazard rate ratios for death were estimated using Cox regression models. The presence of PF-ILD was assessed using recently proposed definitions of relative forced vital capacity (FVC) decline ≥10%, relative diffusion capacity of the lung for carbon monoxide (DLco) decline ≥15% or worsening symptoms or a worsening radiological appearance accompanied by a ≥5 to <10% FVC decline. Results: We identified 102 patients with RA-ILD, and 52% had PF-ILD. Mean follow-up was 3.8 years and median survival was 7.1 years. Thirty-eight patients died during follow-up, and most deaths were from respiratory causes. Predictors of mortality in a multivariate model were DLco and high titres of IgM rheumatoid factor. Conclusion: PF RA-ILD was common and the associated mortality was high.