Gloria Crepaldi

The Multifaceted Aspects of Interstitial Lung Disease in Rheumatoid Arthritis

Interstitial lung disease (ILD) is a relevant extra-articular manifestation of rheumatoid arthritis (RA) that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD) significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP) is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP); other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation.

Cardiovascular Comorbidities Relate More than Others with Disease Activity in Rheumatoid Arthritis

Objectives To explore the influence of comorbidities on clinical outcomes and disease activity in rheumatoid arthritis (RA). Methods In patients included in the cross-sectional observational multicenter international study COMORA, demographics, disease characteristics and comorbidities (hypertension, diabetes, hyperlipidemia, renal failure, ischemic heart disease, stroke, cancer, gastro-intestinal ulcers, hepatitis, depression, chronic pulmonary disease, obesity) were collected. Multivariable linear regression models explored the relationship between each comorbidity and disease activity measures: 28-swollen joint count (SJC), 28-tender joint count (TJC), erythrocyte sedimentation rate (ESR), patient’s and physician’s global assessment (PtGA, PhGA), patient reported fatigue and 28-Disease Activity Score (DAS28). Results are expressed as mean difference (MD) adjusted for the main confounders (age, gender, disease characteristics and treatment). Results A total of 3,920 patients were included: age (mean ±SD) 56.27 ±13.03 yrs, female 81.65%, disease duration median 7.08 yrs (IQR 2.97–13.27), DAS28 (mean ±SD) 3.74 ± 1.55. Patients with diabetes had more swollen and tender joints and worse PtGA and PhGA (MD +1.06, +0.93, +0.53 and +0.54, respectively). Patients with hyperlipidemia had a lower number of swollen and tender joints, lower ESR and better PtGA and PhGA (MD -0.77, -0.56, -3.56, -0.31 and -0.35, respectively). Patients with history of ischemic heart disease and obese patients had more tender joints (MD +1.27 and +1.07) and higher ESR levels (MD +5.64 and +5.20). DAS28 is influenced exclusively by cardiovascular comorbidities, in particular diabetes, hyperlipidemia, ischemic heart disease and obesity. Conclusions Cardiovascular comorbidities relate more than others with disease activity in RA. Diabetes and hyperlipidemia in particular seem associated with higher and lower disease activity respectively influencing almost all considered outcomes, suggesting a special importance of this pattern of comorbidities in disease activity assessment and clinical management.

20 years of experience with tumour necrosis factor inhibitors: what have we learned?

TNF inhibitors are biologic DMARDs approved for the treatment of active RA in mid-1990s. They still represent a valuable therapeutic option to control the activity, disability and radiographic progression of the disease. In the context of TNF inhibitors, there are currently several molecules and different administration routes that provide optimal treatment personalization, allowing us to respond to a patients needs in the best possible way. The increasing use of TNF inhibitors has not only improved the management of RA, but it has also helped in our understanding of the pathogenetic mechanisms of the disease. This review focuses on the basis of this targeted therapy and on the knowledge gained from their use about therapeutic effects and adverse events. Effectiveness analysed from drug registries and safety issues are presented together with recent data on infections (in particular, Mycobacterium tuberculosis and hepatitis B), cancer (lymphoma, skin cancers) and cardiovascular risk.

THU0099 The 2010 classification criteria and a more aggressive treatment strategy improve clinical outcomes in seropositive but not seronegative rheumatoid arthritis

Background Current guidelines recommend an early and intensive treatment in patients diagnosed with rheumatoid arthritis (RA), and the 2010 ACR/EULAR Classification Criteria were developed with the aim of allowing earlier diagnosis and treatment (1,2). Recent studies highlighted some differences in disease activity between seropositive and seronegative RA patients at disease onset (3). Objectives To investigate whether the application of the 2010 ACR/EULAR Classification Criteria and a more aggressive treatment strategy improve clinical outcomes in patients with early RA irrespective of the autoantibody status. Methods 584 early, treatment-naïve RA patients were recruited in the years 2005–2014. RA diagnosis was made according to the ACR 1987 criteria in 2005–2010 (n=360, cohort 1987), and to the 2010 ACR/EULAR criteria in 2011–2014 (n=224, cohort 2010). Patients were classified in autoantibody (Ab)-negative (negative rheumatoid factor (RF) and/or anticitrullinated peptide antibody (ACPA) and Ab-positive (RF and/or ACPA positive). Methotrexate (MTX) was used at the initial dosage of 10 mg/week in cohort 1987, and 15 mg/week in cohort 2010, and progressively increased if low disease activity (LDA) (DAS28≤3.2) was not met. The frequency and predictors of LDA and clinical remission (DAS28<2.6) over 6 months were assessed by Cox regression. Results In Ab-negative patients, LDA and clinical remission were achieved in 62.8% and 37.2% of the cases, and the 2010 cohort did not show significantly improved outcomes (HR [95% CI] 0.86 [0.611.23] for LDA

AB0263 Clinical Onset and Squeezing Test Positivity Influence the Probability to Achieve Clinical Remission at 12 Months in Patients with Early Arthritis

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Perivascular fibrosis and IgG4-related disease: a case report

1.04 [0.651.69] for remission) (Figure 1A,B). In contrast, in Ab-positive patients, the application of the 2010 classification criteria and higher dosages of MTX were associated with increased frequency of LDA after adjustment for confounders (age, sex, prednisone, baseline DAS28

SAT0146 Dissecting the Impact of Comorbidities on Disease Activity in Rheumatoid Arthritis: Ancillary Analysis from the COMORA Study: Table 1.

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Disease-related malnutrition in systemic sclerosis: evidences and implications.

HR [95% CI] 1.39 [1.012]) (Figure 1C). Clinical remission was achieved in 41.3% of the cases, compared to 29.6% in the 1987 cohort (p=0.17) (Figure 1D). Conclusions Early diagnosis and a more aggressive treatment strategy with MTX lead to significantly improved outcomes in autoantibody positive RA. The management of seronegative patients remains suboptimal. References Smolen JS et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis 2016. Aletaha D et al. 2010 rheumatoid arthritis classification criteria: an ACR/EULAR collaborative initiative. Ann Rheum Dis 2010. Nordberg LB et al. Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD naive patients classified according to 2010 ACR/EULAR criteria. Ann Rheum Dis 2017. Disclosure of Interest None declared

085 Worker productivity loss remains a major issue for patients with inflammatory arthritis and osteoarthritis: results from an international worker-productivity study

Background Early diagnosis and prognostic stratification are central issues in the management of early arthritis and rheumatoid arthritis (RA), with several baseline features affecting relevant outcomes 1,2. Objectives To evaluate the influence of referral criteria and pattern of joint involvement on the achievement of DAS28 remission at 12 months in patients with early arthritis. Methods Consecutive patients attending an early arthritis clinic between 2005 and 2013 were enrolled. Referral criteria included joint stiffness>30 minutes, joint swelling and positive squeezing test (ST) at metacarpophalangeal or metatarsophalangeal joints. Baseline demographic features, disease activity, symptom duration and pattern of symptom onset (inflammatory pain, joint stiffness, monoarthritis, oligoarthiritis or polyarthritis) were recorded. Patients classified as RA were treated with methotrexate, while patients with undifferentiated arthritis with hydroxichloroquine. Low-dose oral prednisone could be given. Patients were subsequently treated according to a DAS28 driven step-up protocol in order to achieve low disease activity3, they were seen every 2 months in the first six months and every 3 afterwards, DAS28 was recorded at each evaluation. The outcome of interest was clinical remission (DAS28<2.6) occurring within the first 12 months of follow-up. Analyses on remission were done using a Cox proportional hazard regression analysis, results presented as crude hazard ratios (HR) and 95% confidence intervals (CI) and adjusted for age, gender, symptom duration at presentation, rheumatoid factor and/or ACPA positivity, baseline DAS28, use of steroids and MTX dose. Results A total of 772 patients were included. Mean age (SD) was 57.78 (14.94) years, 73.06% were female, 36.9% had positive rheumatoid factor, 68.6% fulfilled the 2010 criteria for RA, mean DAS28 was 4.60 (1.23) median (IQR) symptom duration was 15.1 (8.8-28.8) weeks (IQR). 72.7% were referred for positive ST, 66.7% for joint effusion, 56.5% for stiffness. 56.7% of patients presented with polyarthritis, 17.3% with inflammatory pain, 15.3% with oligoarthritis, 4.8% monoarthritis, 3.8% stiffness, 1.8% other presentation. The influence of referral criteria and clinical onset on remission achievement at 12 months is collected in Table 1. Conclusions Patients referred for ST positivity are less likely to achieve remission at 12 months than patients referred for swelling or stiffness. Similarly patients with oligoarticular or polyarticular onset achieve remission less frequently. References Symmons DP et al, J Rheumatol. 1998;25(6):1072-7. Machold KP et al, Rheumatology 2007;46:342–349. Sakellariou G. et al, Ann Rheum Dis 2013;72:245-9. Disclosure of Interest None declared

AB0214 Methotrexate in early rheumatoid arthritis: a single-center evaluation of clinical outcome comparing two starting treatment strategies

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibroinflammatory condition which can potentially involve any organ. Some characteristic histopathologic features with lymphoplasmacytic infiltrate, an increased number of IgG4+ cells, storiform fibrosis and obliterative phlebitis are the mainstay for diagnosis. Serum IgG4 levels often increase. We report the case of a patient with perivascular fibrotic lesions involving the aortic arch and the splenic hilum, with a surgical biopsy-proven diagnosis of IgG4-related disease. The patient is now undergoing a low-dose corticosteroid maintenance therapy without evidence of new localizations of the disease. This case highlights the need for increasing awareness and recognition of this new, emerging clinical condition.