Juhász B

Malignancies associated with systemic sclerosis.

The outcome of systemic sclerosis (SSc) has become more favorable during the past years. Respiratory failure or renal crisis became less frequent, therefore more attention should be paid to long-term comorbidities, such as malignancies secondary to scleroderma. The incidence of malignant lymphoproliferative diseases, as well as that of solid tumors are higher in a number of rheumatic diseases including SSc. Some cytotoxic agents, primarily cyclophosphamide used in the treatment of SSc, as well as exposure to chemicals or smoking may further increase cancer risk. We also present malignancies in 218 scleroderma patients undergoing follow-up in our department were assessed for secondary malignancies. Although the number of SSc patients with tumor is relatively small, we compared our cohort to the Health for All Hungarian database and calculated standard incidence ratios (SIR). We identified 11 cases of malignancy in 10 SSc patients (4.6%). One patient had two types of tumor: breast cancer before the onset of SSc and later malignant lymphoma. Half of SSc patients with cancer belonged to the diffuse cutaneous (dcSSc) subtype. The mean age at onset of SSc was 54.6 years, while that at the diagnosis of malignancy was 61.5 years. The mean disease duration of scleroderma at the time of cancer diagnosis was 6.6 years. Five patients died, 4 due to the underlying malignancy. Among the five surviving patients, the mean survival time was 4.9 years. Altogether 3 patients had non-Hodgkins lymphoma, 2 had bronchial cancer, 2 had breast cancer, one had leiomyosarcoma of the leg, one had esophageal cancer, one had cervix cancer and one had skin cancer. In comparison to the Health for All database, the overall SIR of all malignancies in SSc was 1.07 (CI: 0.82-1.38) varying between 5.8 and 52.4 in different tumor types. Only one cancer patient received cyclophosphamide therapy. In conclusion, secondary tumors including lung, skin and breast cancer, as well as lymphomas are more common in SSc than in the general population. The adequate treatment and follow-up of scleroderma patients may help us to lower the risk of malignancies secondary to SSc.

A4.3 Effects of anti-TNF therapy on markers of bone homeostasis in rheumatoid arthritis and ankylosing spondylitis

Background and objectives Uncoupling of bone resorption and formation has been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Generalised bone loss and erosions are characteristic for RA, while in AS, bone formation overrides resorption. The RANKL/OPG and the Wnt/DKK-1/sclerostin systems have been implicated in disturben bone homeostasis in arthritides. Anti-TNF biologics may beneficially influence erosions and bone loss in RA, however, they have little effect on bone formation in AS. In the present study, we assessed the effects of 1-year anti-TNF treatment on various bone biomarkers. Patients and methods Altogether 43 arthritis patients including 30 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 13 AS patients treated with ETN were included in a 12-month follow-up study. Disease activity (DAS28 or BASDAI), CRP, IgM rheumatoid factor, anti-CCP, calcium (Ca), phosphate (P), osteocalcin (OC), P1NP, CTX, BNP, sclerostin (SOST), DKK-1, soluble RANKL (sRANKL), cathepsin K (cathK) and vitamin D3 (vitD) levels were assessed at baseline, as well as 6 and 12 months after treatment initiation. Results Anti-TNF treatment was highly effective in both diseases, as the mean DAS28 decreased from 6.32 to 3.16 (p = 0.02) in RA, mean BASDAI decreased from 5.87 to 1.84 (p < 0.001) in AS. In RA, anti-TNF treatment significantly decreased DKK-1 (60.5 ± 28.9 pM and 54.7 ± 20.8 pM, p = 0.036) and CathK (28.7 ± 6.2 pm and 26.8 ± 4.0 pm, p = 0.014) but increased SOST (107.0 ± 47.5 pM and 131.2 ± 85.2 pM, p = 0.04) levels from baseline to 12 months, respectively. In RA, ETN and CZP treatment also increased OPG/sRANKL ratio after 6 months (51.9) vs. baseline (43.9) (p = 0.01). In AS, ETN therapy significantly increased the bone formation marker P1NP (49.4 ± 19.0 pM and 56.9 ± 28.7 pM, p = 0.03) and SOST (70.6 ± 29.0 pM and 82.4 ± 48.3 pM, p = 0.022) levels from baseline to 12 months, respectively. ETN therapy also increased OPG/sRANKL ratio after 6 months (44.5) and 12 months (46.9) compared to baseline (34.5) in AS (p < 0.01). Both baseline and 12-month SOST levels were significantly lower in AS compared to RA (p < 0.001). When RA and AS data were pooled, TNF inhibition resulted in significantly decreased DKK-1 (p = 0.035) and cathK (p = 0.008) but increased P1NP (p = 0.04) and SOST (p = 0.04) after 12 months. In this study, biologics did not affect Ca, P, OC, CTX, BNP, vitD levels. Conclusions In a mixed cohort of RA and AS patients, anti-TNF therapy resulted in a restoration of bone homeostasis by decreasing DKK-1 and CathK, increasing P1NP, SOST and OPG/sRANKL ratio. Lower SOST levels in AS compared to RA, as well as the induction of bone formation over resorption may account for the inefficacy of TNF inhibitors on syndesmophyte formation in AS.

SAT0346 Simultaneous assessment of bone loss in rheumatoid arthritis using peripheral quantitative CT and DEXA

Background Rheumatoid arthritis (RA) has been associated with secondary bone loss leading to osteoporosis in 60-70% of patients. Bone loss involves both the trabecular and cortical compartment. Traditional DEXA is not sufficient to assess bone loss in various compartments, however peripheral quantitative CT (pqCT) is. Objectives Simultaneous assessment of bone density was performed using DEXA and pqCT. Bone assessments were correlated with clinical parameters and ACPA status. Methods pqCT assessment was performed by a Stratec XCT-2000 instrument. Altogether 48 RA female patients and 10 female healthy controls were recruited. Forearm pqCT, as well as lumbar spine and femoral neck DEXA assessments were performed. Anti-CCP was determined by a second generation ELISA. Results The mean age of patients was 53.6±13.8 years and the mean disease duration was 13.5 years. Altogether 75% of patients were anti-CCP positive. In RA, total, cortical and trabecular attenuation, as well as bone density were decreased compared to controls as determined by pqCT (p<0.005). Total and cortical pqCT density exerted inverse correlation with age, while total, cortical and trabecular pqCT showed positive correlation with lumbar and femoral neck BMD as determined by DEXA (p<0.05). Trabecular, but not cortical pqCT density inversely correlated with anti-CCP positivity (p=0.04). Conclusions In RA, pqCT revealed cortical and trabecular bone loss. Moreover, anti-CCP, a marker of autoimmunity and a prognostic factor associated with joint erosions, also correlate with trabecular osteoporosis. In RA, as well as primary osteoporosis, pqCT may be a useful tool to assess trabecular and cortical bone loss. Disclosure of Interest None Declared