Konstantinos Thomas

Hepatitis B Reactivation in Rheumatic Diseases : Screening and Prevention

Hepatitis B virus (HBV) reactivation (HBVr) has been an increasingly recognized and appreciated risk of immunosuppressive therapies in rheumatic patients. Despite its potential for significant morbidity and mortality, HBVr is a fully preventable complication with appropriate pretreatment screening and close monitoring of susceptible patients. Better knowledge of the risk for HBVr with the different antirheumatic agents and the establishment of the new-generation oral antivirals in clinical practice has greatly improved the design of screening and therapeutic algorithms. In this review, all available data regarding HBVr in rheumatic patients are critically presented and a screening and therapeutic algorithm is proposed.

Prevention of HBV reactivation in patients treated with biologic agents

ABSTRACT Owing to the sensitive equilibrium between the hepatitis B virus (HBV) and the host’s immune system in infected and exposed individuals, the immunosuppression caused by biologic treatment has been strongly linked to HBV reactivation (HBVr). HBVr in the setting of biologic therapy is a cause of considerable morbidity, hospitalization, interruption of treatment and mortality. However, recent literature has established that this is a largely preventable problem. Thus, it is essential for clinicians using biologic agents to be aware of HBVr potential and screen all susceptible patients. The risk for HBVr may vary depending on the host’s HBV infection status and the potency of immunosuppression. The appropriate pre-emptive antiviral prophylaxis or monitoring for individuals at risk is emphasized in the latest evidence-based guidelines, but a number of unanswered questions remain.

Infections and vasculitis.

Purpose of review To review recent evidence for infection rates in patients with systemic vasculitides, the role of specific infectious agents in the pathogenesis of vasculitis and recent breakthroughs in the treatment of virus-associated vasculitides. Recent findings In well designed recent studies, infections were found to be common during the first 6–12 months in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) and giant cell arteritis (GCA) and to contribute significantly to increased mortality during this period. New therapeutic schemes with lower cyclophosphamide doses and shorter corticosteroid courses were associated with decreased infectious rates in elderly patients with AAV whereas a prednisone dose greater than 10 mg/day at the end of the first year were associated with increased infectious-related mortality in patients with GCA. Recently, a potential role for varicella zoster virus in GCA pathogenesis has been proposed but more data are needed in order to establish a causal relationship. Finally, preliminary data show excellent short-term efficacy and safety of the new, interferon-free, oral antiviral agents in the treatment of hepatitis C virus-associated cryoglobulinemic vasculitis. Summary Infections continue to be one of the main causes of mortality in patients with systemic vasculitides, emphasizing the need for safer immunosuppressive therapies and appropriate prophylaxis.

Immunization in patients with inflammatory rheumatic diseases

Immunization represents the most efficient and simplest intervention to prevent certain viral and bacterial infections in the general population as well as in the vulnerable population of patients with inflammatory rheumatic diseases treated with immunosuppressives. Here, we present an updated review of literature data regarding the safety and efficacy of immunizations against different pathogens in rheumatic patients treated with conventional immunosuppressives or the newer biologic agents while at the same time we provide practical guidance for the appropriate vaccine administration in this patient population.

Individual Drugs in Rheumatology and the Risk of Infection

The advances in the therapeutics of rheumatic patients with the introduction of biologic therapies have led to a better control of diseases with inadequate response to conventional treatments and to an improvement of the functional status of these patients. Despite this progress, the risk of infections in patients under biologic or conventional treatments has not been reduced, partly because more elderly patients or patients with comorbidities are considered eligible for immunosuppressive or disease-modifying treatments. Rheumatologists should be aware of the specific patterns of infection risk that accompany these, especially the newer, treatments and should be vigilant for signs and symptoms of infection in patients with rheumatic diseases. Appropriate screening for and treatment of chronic hepatitis B virus infection and latent tuberculosis significantly reduce the risk for reactivation in patients under therapy. Chemoprophylaxis of patients susceptible for Pneumocystis jirovecii pneumonia eliminates almost completely the risk for acquisition of this potentially lethal infection in eligible patients. Appropriate vaccinations of rheumatic patients treated with antirheumatic therapies should be part of the daily clinical practice of physicians caring for patients with rheumatic diseases.

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.

Recurrent ventricular arrhythmia in a patient with aortitis and myocardial inflammation due to possible immunoglobulin G4-related disease: Letters to the Editor

markers. This case demonstrates a diagnostic challenge and is an important lesson in not relying on CK to rule out muscle involvement, especially by vasculitis. An inflammatory myopathy was considered unlikely with negative autoimmune myositis serology and electromyography, and was ruled out with a biopsy. One important differential was an aortic endograft infection which was discounted with multiple negative blood cultures and bland PET imaging of the aorta. The biopsy contained features of calciphylaxis highlighting the importance of considering this life threatening differential diagnosis as there are multiple case reports wherein calciphylaxis was misdiagnosed as vasculitis. A recent case series analysed 11 cases of biopsy proven isolated lower limb vasculitis and found that disabling muscle pain, fevers and raised inflammatory markers were core features and on prologued follow up extra musculoskeletal involvement was absent. The cases were typically initially steroid responsive; however 90% of patients experienced a relapse on tapering and greater than 50% required further immunosuppressive agents. It has also been proposed that isolated lower limb vasculitis may be a particular manifestation of polyarteritis nodosa that left untreated would progress to involve other organ systems. Another possibility would be a vasculitis within the giant cell arteritis (GCA) spectrum. Against this, however, upper limb involvement, limb claudication, a lack of constitutional symptoms and PET positivity were more predominant in previously reported cases of GCA with limb involvement and there were no giant cells seen in this patient’s muscle biopsy. This case also demonstrates the utility of MRI and PET in the diagnosis of vasculitis. The normal PET despite active large vessel vasculitis highlights the unproven utility of PET in the lower limb vasculature. The role of MRI in helping to diagnose lower limb restricted vasculitis is supported by a case series, which found that muscle damage was characterised by hyperintense T2 signals and slow short T1 inversion recovery sequences. The isolated lower limb vasculitis case series also demonstrated the value of MRI in monitoring treatment response. In conclusion, we have reported an important presentation of isolated lower limb medium–large vessel vasculitis, and demonstrated an approach to diagnosis and management that may instruct future cases of this protean disease.

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

AB0654 Efficacy and Safety of Rituximab in Patients with Anca Associated Vasculitis in Real Life

Background Rituximab (RTX) is a novel, recently approved therapeutic agent for the treatment of active ANCA-associated vasculitis (AAV, Granulomatosis with polyangiitis-GPA, Microscopic polyangiitis-MPA) with limited data available from daily clinical practice. Objectives To study the efficacy and safety of RTX in patients with AAV in real life settings. Methods Retrospective study of all patients with active AAV treated with RTX in our tertiary center between 2010 and 2015. Results 16 patients with active AAV were included (GPA n=12, MPA n=4); 50% females with a mean age of 61.8±13.9 years and median disease duration of 33.5 months. The majority of patients had generalized disease (88%) and the most commonly involved organs were lungs (75%), kidney (63%), joints (50%) and ENT (31%). The patients were followed for a mean period of 21.5±16.1 months. Eleven (68%) patients were treated with RTX due to resistant or relapsing disease and 5 (32%) received RTX as initial treatment. Seven patients received 1 cycle, one patient 2 cycles and 8 patients received ≥3 cycles of RTX (1 gm x 2, 15 days apart). Among patients who received ≥1 cycle of RTX (n=9), 6 received RTX on a regular basis (every 6 months) and 3 at relapse. During treatment, a statistically significant improvement in disease activity was observed (BVAS/WG before RTX was 4.8 and decreased to 0.9 and 0.8 at 6 and 12 months, p=0.001 and 0.003 respectively). At 6 months, 87% of patients (13/15) responded to therapy (6 showed complete and 7 partial response). Additionally, one patient who had not responded at 6 months demonstrated complete response at 9 months. Among the 13 responders, 6 (46%) relapsed during follow up. The majority of relapses were minor (5/6, 83%) and occurred mainly in patients not receiving RTX in a regular basis (4/6, 67%). One patient with GPA and fulminant pulmonary-renal syndrome died from septic shock one month after RTX administration (6%). No other serious infections or allergic reactions were noticed during the follow up period. Conclusions These real life data confirm the excellent efficacy and safety of RTX in patients with active newly diagnosed or relapsing AAV. Acknowledgements This work was supported in part by research grants from the Special Account for Research Grants (S.A.R.G.), National and Kapodistrian University of Athens, Athens, Greece. Disclosure of Interest None declared