Evripidis Kaltsonoudis

Demyelination and other neurological adverse events after anti-TNF therapy

Tumor necrosis factor (TNF) α inhibitors are an essential therapeutic option for several inflammatory diseases, like rheumatoid arthritis, spondyloarthropathies and inflammatory bowel diseases. As TNFα antagonists have become increasingly utilized, there have been a number of reports of neurological adverse events in patients receiving anti-TNFα therapy. The frequency of central nervous system adverse events after initiation of anti-TNFα therapy is unknown. However, questions have been raised about a possible causal association. Although several hypotheses have been proposed in an attempt to explain the possible relationship between TNFα antagonist and demyelination, none is considered to be adequate. Thus, in this report we deal with the implication of TNFα in multiple sclerosis and we discuss the possible relationship of TNFα antagonist and demyelinating diseases.

Fertility in male patients with seronegative spondyloarthropathies treated with infliximab

OBJECTIVES The majority of patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are affected during their peak reproductive years. Tumor necrosis factor (TNF)α plays a pivotal role in the pathogenesis of both diseases. Today, anti-TNFα blockers are an essential treatment for these patients. To identify male patients who achieved pregnancy development during their management with anti-TNFα blockers (infliximab). METHODS We reviewed the data of 65 patients with AS and 30 patients with PsA who were followed-up in our rheumatology outpatients clinic and they were on infliximab therapy between January 2001 and December 2010. RESULTS We identified overall seven male patients with AS and three male patients with PsA who had fathered 14 healthy infants. Moreover, we recognized one man with PsA who was on infliximab and on concomitant therapy with MTX at the time of conception, whose wife had to proceed to therapeutic abortion due to congenital abnormalities of the fetus (hydrocephalia), while she was on the first trimester of pregnancy. CONCLUSIONS We described male patients with AS and PsA who demonstrated no fertility problems while they were on infliximab treatment. The data designated in this report provide some supportive evidence for the safe use of infliximab in male patients who are affected of those inflammatory diseases during their peak reproductive years.

Adalimumab in the treatment of rheumatoid arthritis.

Adalimumab (ADA), a fully human monoclonal antibody against TNF-α is indicated for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, Crohns disease, ulcerative colitis and psoriasis. In RA, it may be prescribed in combination with methotrexate or other disease-modifying antirheumatic drugs or as monotherapy. Studies comparing ADA with other TNF-α inhibitors are limited and are based mainly on meta-analyses of randomised controlled trials and large observational cohorts. In this study, the effectiveness and safety of ADA is compared with that of etanercept and infliximab.

Unmet needs in the treatment of rheumatoid arthritis. An observational study and a real-life experience from a single university center

OBJECTIVES To estimate the size of unmet needs in the treatment of early Rheumatoid Arthritis (eRA), using all the conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or biological DMARDs (bDMARDs) in a long-term observational study. MATERIALS AND METHODS 538 patients with eRA were evaluated. The 2010 ACR/EULAR classification criteria were used. All patients were csDMARDs and bDMARDs-naive with disease duration less than one year. They were treated according to EULAR and ACR recommendations for RA. All the csDMARDs and bDMARDs were used. Clinical, laboratory findings with the disease activity score-28 and treatment decisions were all recorded as well as adverse drug reactions, reason of therapy termination, disease complications and comorbidities. RESULTS Methotrexate (58%) and Infliximab (37%) where the first csDMARD and bDMARD choice respectively. During follow-up, 14 patients were lost and 7 developed comorbidities. The final results are referred to 517 patients. Among those, 66% were treated with csDMARDs as monotherapy or in combination therapy with sustained low disease activity (LDA). However, 3.2% from this group neither achieved LDA, nor received bDMARDs, due to comorbidities. On the other hand, 34% were treated with bDMARDs with or without csDMARDs. The majority of them demonstrated sustained LDA. From this group, 17.7% never achieved LDA, despite that they switched and received all bDMARDs. Thus, 20.9% of our patients never achieved LDA. CONCLUSIONS Using the current recommendations for RA therapy we successfully treated the majority of our patients. However, we found that the size of gap and the unmet needs for treatment is about 20%.

Multicenter Cross-sectional Study of Patients with Rheumatoid Arthritis in Greece: Results from a cohort of 2.491 patients

Aim of the study: To evaluate the current disease characteristics, treatment and comorbidities of rheumatoid arthritis (RA) in Greece. Methods: Multicenter, cross-sectional study with a 9-month recruitment period between 2015 and 2016. Demographics, disease characteristics, treatment and comorbidities were collected via a web-based platform. Results: 2.491 RA patients were recruited: 96% from tertiary referral centers, 79% were females with a mean age of 63.1 years and disease duration of 9.9 years. Fifty-two percent were rheumatoid factor and/or anti-CCP positive, while 41% had erosive disease. Regarding treatment, 82% were on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), 42% on biologic DMARDs (TNFi: 22%, non-TNFi: 20%) and 40% on corticosteroids (mean daily dose: 5.2 mg). Despite therapy, 36% of patients had moderate and 12% high disease activity. The most frequent comorbidities were hypertension (42%), hyperlipidemia (33%), osteoporosis (29%), diabetes mellitus (15%) and depression (12%). Latent tuberculosis infection (positive tuberculin skin test or interferon gamma release assay) was diagnosed in 13 and 15.3% of patients, respectively. Regarding chronic viral infections, 6.2% had history of herpes zoster while 2% and 0.7% had chronic hepatitis B and C virus infection, respectively. A history of serious infection was documented in 9.6%. Only 36% and 52% of the participants had ever been vaccinated against pneumococcus and influenza virus, respectively. Conclusion: This is one of the largest epidemiologic studies providing valuable data regarding the current RA characteristics in Greece. Half of patients were seropositive but despite therapy, half displayed residual disease activity, while preventive vaccination was limited.

AB0542 Multiple sclerosis in patients with primary sjÖgren’s syndrome

Background Imaging and histopathologic studies in patients with primary Sjögren’s Syndrome (pSS) have demonstrated white matter lesions which are indistinguishable from those observed in multiple sclerosis (MS). Objectives The purpose of this study was to evaluate the frequency of MS in a cohort of patients with pSS. Methods One hundred and twenty-one patients with pSS had been evaluated and followed up in the outpatient Rheumatology Clinic at predefined times since 1994. All patients were classified according to the 2016 ACR-EULAR criteria for SS. During follow-up the clinical, laboratory and imaging findings were all recorded. In addition, Magnetic Resonance Imaging and electrophysiological studies as well as spinal fluid analysis were performed when indicated. The diagnosis of MS was based on the 2010 revised McDonald criteria. Results Seven patients were diagnosed as having MS. All patients with MS were female. Mean age at the time of MS diagnosis was 65.5±3.6 years, while pSS has been diagnosed at the mean age of 54.4±3.2 years. Mean time of MS development was approximately 10 years after the pSS diagnosis. pSS patients who developed MS had severe sicca symptoms without other extraglandular manifestations and had positive Ro (SSA) antibodies and a positive minor salivary gland biopsy. pSS patients with MS development were treated appropriately in the Neurology department with biological medications with some improvement of the sicca symptoms. Conclusions We found that 5.8% of pSS patients as having MS. This percentage of patients clearly indicates the possibility for the coexistence of a second autoimmune disease with similar if not common pathogenetic mechanisms. Thus patients with pSS should be evaluated carefully and screened appropriately for MS when indicated. Disclosure of Interest None declared

Dermatomyositis sine myositis – Case presentation

In this case, we present a patient with unilateral salivary gland enlargement and periorbital edema with erythematous rash. We discuss the differential diagnosis and the relevant therapy.

SAT0176 Patterns of biologic dmard monotherapy in a large nationwide rheumatoid arthritis cohort: data from 1036 patients

Background There are limited literature data regarding the characteristics of rheumatoid arthritis (RA) patients treated with biologic DMARD (bDMARD) monotherapy. Objectives To evaluate the disease and treatment characteristics of RA patients treated with bDMARD monotherapy. Methods Multicenter, cross-sectional RA epidemiological study in Greece (06/2015–05/2016, ERE RA Study Group). Demographics, disease characteristics, treatment and co-morbidity data were collected via a web-based platform Results 1036 RA patients treated with bDMARDs were identified during the one year recruitment period (female: 82%, mean age: 61.5±13 years, mean disease duration: 12.5±8.9 years, mean DAS28-ESR: 3.4±3.3). Among them, 26% (n=273) were receiving bDMARDs as monotherapy and 8% (n=23) of them had never tried conventional synthetic DMARDs (csDMARDs) before; The latter group (n=23) compared to the csDMARD-exposed (92%, n=250) group, had more often co-morbidities [cardiovascular disease (22% vs. 8%, p=0.029), chronic hepatitis (13% vs. 3%, p=0.02), hypertension (57% vs. 38%, p=0.08), COPD (13% vs. 4.4%, p=0.07)] or were active smokers (41% vs. 14%, p=0.001). csDMARD discontinuation was mainly due to adverse events (AEs, 58%) followed by inadequate response (IR, 44%). Compared to the cs- and b-DMARD combination therapy group, monotherapy treated patients were more frequently seropositive (64% vs. 57%, p=0.003), had lower DAS28-ESR (3.2 vs 3.5, p=0.009) and were more likely to have discontinued csDMARDs for AEs (58% vs. 21%, p<0.001) or IR (44% vs. 27%, p<0.001). Tocilizumab (22.3% vs. 12.7%, p<0.001) and rituximab (19.8% vs. 13.5%, p=0.013) were utilized more often, whereas adalimumab less often (8.8% vs. 14.8%, p=0.012) as monotherapy compared to as part of combination therapy. Conclusions In our large RA cohort, one out of four bDMARD treated patients, were receiving bDMARDs as monotherapy. Co-morbidities rather than RA characteristics influence the initial decision for bDMARD monotherapy whereas among those starting combination cs- and b-DMARD therapy, the majority discontinue csDMARDs due to AEs. Acknowledgements Grant support from the Hellenic Rheumatology Society and Professional Association of Rheumatologists. Disclosure of Interest None declared

SAT0118 Dyslipidemia Is Undertreated in Patients with Rheumatoid Arthritis: Results from A Large Cohort of RA Patients in Daily Clinical Practice

Background Existing guidelines advocate aggressive management of dyslipidemia in rheumatoid arthritis (RA) patients according to cardiovascular disease (CVD) risk scores generated for the general population (SCORE). More specific RA scores such as the ERS-RA score have not been extensively studied. Objectives To evaluate the use of lipid-lowering agents for CVD prevention (primary/secondary) in RA patients according to different CVD risk scores (SCORE, ERS-RA). Methods Prospective, multicenter (12 hospitals, 6 private offices), cross-sectional, epidemiological study in Greece (06/2015–01/2016, RA Study Group). Demographics, disease characteristics, treatment and comorbidities were collected and SCORE/ERS-RA were calculated. Results Among 1475 patients, 178 (12%) had CVD (44% coronary artery disease, 44% peripheral vascular disease, 27% stroke) and 43% were not receiving any hypolipidemic therapy. From those on therapy, only 12% achieved an LDL-cholesterol (LDL-C) level <70 mg/dl while 48% had LDL-C<100 mg/dl. 859 patients without CVD, diabetes or hypolipidemic therapy were further analyzed (79% women, mean age 59.5 yrs, mean disease duration 3.4 yrs, mean DAS28-ESR 3.4, mean HAQ 0.45). Complete data for SCORE calculation were available in 225/859 patients (26%). When stratified according to CVD risk, 31.5%, 66%, 2% and 0.5% of patients had a SCORE of <1% (low risk), ≥1 to <5% (moderate), ≥5 to <10% (high) and ≥10% (very high), respectively. In moderate risk (1–5%) patients, 78% had an LDL-C>100 mg/dl while among high or very high risk (≥5%) patients, 100% had an LDL-C>70 mg/dl (target groups for drug therapy). Among 996 patients (40–75 yrs old), without CVD events, there were 99 diabetic patients (10%) and less than half (48%) were on hypolipidemic therapy. For the rest, the ERS-RA score was calculated (619/897, 69% with available data); 50% of them (308/619) had a 10-year risk of ≥7.5% (therapeutic cutoff) but only 40% of patients in this group were being treated. Conclusions A substantial proportion of RA patients with established CVD or diabetes do not receive lipid-lowering therapy or they do not achieve therapeutic targets. Among those without CVD or diabetes, more than half belong to moderate to high CVD risk groups and are not receiving appropriate hypolipidemic therapy. Acknowledgement Supported by grants from the Hellenic Rheumatology Society and Professional Association of Rheumatologists. Disclosure of Interest None declared