FRI0056 Clinical features at the onset of lymphoproliferative disorder in patients with rheumatoid arthritis
Authors: D. Kobayashi, S. Ito, Y. Wada, I. Narita, K. Nakazono
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is intrinsically associated with an increased incidence of lymphoproliferative disorders (LPDs). Furthermore, treatment with immunosuppressing agents, such as methotrexate (MTX) sometimes leads to the development of immunosuppressing agents related LPDs. Thus the development of LPDs is an increasingly important issue. However, previous studies focused on the pathological features and regression of LPDs after ceasing MTX administration, and evidence that could allow for the early diagnosis of LPDs in patients with RA is lacking. <h3>Objectives</h3> We surveyed the clinical course of patients with RA who developed LPDs at our hospital, with a focus on the clinical course and laboratory findings leading to their development. <h3>Methods</h3> Patients with RA who were treated at <sup>Niigata Rheumatic Centre between April 2011</sup> and December 2017 were analysed. Patient data were obtained retrospectively from medical records. Twenty-nine patients (14 men, 15 women) developed a LPD (LPD group). We compared them with 87 patients without LPD (non-LPD group), who were matched for age, sex, and RA duration among 2628 patients with RA who attended our outpatient department in 2017. Data indicated are median (IQR<sub>1/4</sub>–<sub>3/4</sub>) values. <h3>Results</h3> The median patient age was 71.0 (64.0–74.0) years, and the duration of RA was 16.0 (10.0–22.0) years in both groups. Twelve patients were diagnosed with diffuse large B cell lymphoma, 5 with Hodgkin lymphoma, and 4 with T cell lymphoma; 8 patients had other diagnosis. Of 29 patients, 23 were treated with MTX, 10 with tacrolimus, 8 with biological disease-modifying antirheumatic drugs (bDMARD). Twenty-two patients had Steinbrocker stage-IV RA. Multivariate analysis showed that Steinbrocker stage IV and MTX treatment were risk factors for the development of LPDs, with hazard ratios of 4.65 and 3.32, respectively. In the LPDs group, although the C-reactive protein level (CRP) level and lactate dehydrogenase (LDH) level significantly rose (CRP, 0.10 [0.090–0.20] mg/dL 6 months before LPD diagnosis to 1.9 [1.1–3.8] mg/dL at LPD diagnosis, LDH, 198.0 [184.0–230] to 310 [210–489] IU/L), neither the tender joint count (TJC) and swollen joint count (SJC), nor matrix metalloproteinase-3 (MMP-3) level showed any significant change. On the contrary, CRP and LDH levels, as well as TJC, SJC, and MMP-3 level did not change significantly at the 6 month follow-up in non-LPDs group. LDH, MMP, and CRP ratios were calculated as the ratio of them at LPD diagnosis to those at 6 months before diagnosis. CRP and LDH ratios were significantly higher in the LPD group (CRP, 1.00 [0.65–1.75] in the non-LPD group vs 9.50 [2.40–23.0] in the LPD group; LDH, 1.00 [0.93–1.09] in the non-LPD group vs 1.46 [1.17–2.04] in the LPD group). However, the MMP-3 ratio was not different significantly between the non-LPD and LPD groups (1.00 [0.88–1.12] vs 0.98 [0.85–1.21]). MMP-3 ratio/CRP ratio was significantly lower in the LPD group than in the non-LPD group (0.0979 [0.036–0.384] vs 1.00 [0.54–1.67]). The receiver operating characteristic curve suggested that MMP-3 ratio/CRP ratio &lt;0.476 was the best cut-off point for the prediction of LPD development, with a sensitivity of 90.9%, specificity of 79.0%, and an area under the curve of 0.894. <h3>Conclusions</h3> LDH elevation, and CRP elevation that is disproportionate to TJC, SJC, and MMP-3 level might indicate underlying LPD. <h3>Disclosure of Interest</h3> None declared