M. Sousa

Transfer factor therapy in a case of complex immunodeficiency

Abstract A young woman with unclassified complex immune deficiency disease characterized by relapsing skin ulcerations, greatly depressed cellular immunity, absent serum IgA, and inability to develop circulating antibodies to typhoid vaccine, was treated twice with the dialyzable transfer factor from normal persons. Following such therapy she showed clinical improvement and strong delayed skin sensitivity to Candida , streptokinase-streptodornase, and moderate, rather short-lived hypersensitivity to PPD. In addition, she could be sensitized to dinitrochlorobenzene and her leucocytes responded normally to phytohaemagglutinin; all these manifestions of cellular immunity had been absent prior to therapy. She acquired the capacity to develop anti-typhoid antibodies. These findings appear to indicate that dialyzable transfer factor not only transfers delayed-type hypersensitivities preexisting in the donor but is also able to remedy hitherto unspecific defects existing in certain forms of immune deficiency.

THU0536 Remission and Re-Treatment of Patients with Paget's Disease of Bone Treated with Zolendronic Acid – A Single Center 10 Year Experience

Background Treatment of Pagets Disease of Bone (PDB) has been revolutionized by the use of zolendronic acid (ZA). Patients usually have a dramatic response to treatment with normalization serum alkaline phosphataise (ALP) levels and a longer period of clinical remission, compared with other class agents. Data from long-term use are scarse. Objectives Evaluate the effectiveness and safety of ZA in PDB patients, as well as remission, re-treatment rates and side effects in our outpatient population since 2005. Methods A retrospective study of PDB patients treated with 5 mg ZA intravenous infusion at our day-care center. Follow up time, demographic and clinical characteristics, previous therapeutic agents, rate of response, number and reasons of re-treatment(s) and rates of adverse events were collected. A descriptive statistic analysis was made. Results 48 patients, 60% female, mean age of 75 years, with a median time since the diagnosis of 12.3 years. The disease was poliostotic in 73% of the patients and pelvis (65%), skull (29%) and spine (27%) were the most common pagetic localizations. Deafness was present in 12.5% and 65% had hip involvement. 44% patients had been treated with another biphosphonate agent previously. Response rates were 97.9% at 1 year, 87.2% after 2 years and 95.1% after 3 years. The mean ALP levels before ZA infusion was 290 UI/L and after 112 UI/L. Sixteen patients needed a re-treatment in the period of follow up, minimum of 1 year after the ZA infusion and maximum of 8 years after. 56.3% due to raised of ALP levels and 43.8% due pain/ hip involvement. Four patients needed a third infusion due to hip involvement, and 2 of them a forth infusion due to the same reason. All of the patients re-treated due to hip involvement had severe hip involvement at time of diagnosis. In our population, 2 patients achieved 10 years remission, 5 patients 9 years remission and 10 patients 8 years remission with a single ZA infusion. Recording adverse effects were: 14.6% Flu like symptoms (7 patients), 2% assintomatic hypocalcemia (1 patient) and no reports of osteonecrosis or fractures. All of these effects were reported after the first ZA infusion. Conclusions In our population, we find high long-term sustained remission rate. Only sixteen patients needed re-treatment. Patients maintained sustained remission up to 10 years of a single ZA infusion. Incidence of adverse events was similar to the reported in the literature. References Reid IR, Miller P, Lyles K et al. Comparison of a Single Infusion of Zolendronic Acid with Risendronate for Pagets Disease. N Eng J Med. 2005 Set:353(9):898–908 Reid IR, Brown JP, Levitt N et al. Re-treatment of relapse Pagets disease of bone with zolendronic acid: results from an open-label study. Natur BoneKEy Report 2. 2013 Nov: 442: 1–3 Reid IR, Lyles K, Brown JP et al. A Single Infusion of Zolendronic Acid Produces Sustained Remissions in Paget Disease: Data from 6.5 years, JBMR. 2011 Sep 26 (9):2261–70 Devogelaer JP, Geusen P, Daci E et al. Remission over 3 years in patients with Paget disease of bone treated with a single intravenous infusion of 5 mg zolendronic acid. Calcif Tissue Int. 2014 Mar:94(3):311–8 Disclosure of Interest None declared

AB0965 Single Nucleotide Polymorphisms in TNFA1P3 and PTPN2 Are Associated with a Poor Outcome in Juvenile Idiopathic Arthritis. Data From Reuma.PT

Background Genetic variants have been identified associated with the susceptibility to Juvenile idiopathic arthritis (JIA). Little is known about the genetic determinants of disease severity and long-term outcomes. Objectives This study aimed to assess the genetic determinants of poor outcome in Portuguese patients with JIA. Methods Our study relied on Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA receiving biological therapies and synthetic DMARDs. Subject and disease characteristics of patients with the diagnosis of JIA were collected prospectively and a blood sample for DNA analysis stored. Poor prognosis was defined as CHAQ/HAQ >0.75 at the last visit and/or the need for biological therapy. A previously selected panel of 31 single nucleotide polymorphisms (SNPs) was studied to verify if there was any association with poor prognosis. Results 291 patients out of the 812 JIA patients registered in Reuma.pt, had a blood sample to perform the genetic analysis. From those, 267 had CHAQ/HAQ registered. The mean age was 19.9±11.3 years, 65% females. The mean age at JIA onset was 6.9±4.7 years. Of the 267 patients analyzed, 85 match our criteria of poor prognosis. In univariate analysis, including all disease categories of JIA, we found significant associations with poor prognosis for allele A of TNFA1P3/20 rs6920220, allele G of TRAF1/C5 rs3761847 and allele G of PTPN2 rs7234029. In multivariate models, the associations for TNFA1P3/20 rs6920220 (odds ratio =1.88 [95% CI 1.13-3.14]) and PTPN2 rs7234029 (OR 1.75 [1.03-3.00]) remained significant at the 5% level, while TRAF1/C5 rs3761847 (OR 1.53 [0.95-2.47]) was no longer significant. Conclusions TNFA1P3/A20 and PTPN2 were associated with poor prognosis in Portuguese patients with JIA. These genes were also associated with susceptibility to JIA. Further studies in independent populations are needed to strengthen the knowledge in this field. Disclosure of Interest None declared

AB0881 Biologic Disease Modifying Anti-Rheumatic Drug Use in the Treatment of Juvenile Idiopathic Arthritis: Data from the Rheumatic Diseases Portuguese Register, Reuma.Pt

Background The Portuguese Society of Rheumatology developed the Rheumatic Diseases Portuguese Register (Reuma.pt) encompassing also Juvenile Idiopathic Arthritis patients followed by rheumatologists and pediatricians. Objectives 1. To obtain an overview of biological agents use in Portuguese children with JIA. 2. To assess the effectiveness and safety of biological therapy at 6 months and 1 year of treatment. Methods We retrieved data from Reuma.pt, until December 2013. We collected baseline patient and disease characteristics of patients with JIA who started treatment with biological agents. Follow-up data were analyzed and are presented at 6 months and 1 year. Disease activity was assessed using the number of active joints, ESR and CHAQ. Results 812 patients with JIA,227 received biological therapy.The mean age at disease onset of patients treated with biologic DMARDs was 6.9±4.7years and the mean age for starting biological therapy was 16.1±9.4years. The most common JIA categories were polyarticular RF negative (23.3%), polyarticular RF+(17.5%) and extended oligoarticular (16.0%).The median duration of the first biological agent was 5.76years. Most patients were treated with antiTNF as first line (90.3%):etanercept 69.2%,adalimumab 12.8%,infliximab 8.4%. Mean baseline active joint count was 5.1±5.8, decreasing to 1.2±2.4 and 1.0±3.1 after 6 months and 1 year of therapy. Mean ESR was 33.9±25.3 mm/1sth and 26.9±23.9 and 19.1±180 after 6 months and 1 year. CHAQ decreased from 0.8±0.7 to 0.4±0.5 and 0.4±0.5 at 6 months and 1 year. 14.1% switched once to other biological therapy (3.08% in the first 6 months,4.4% in the first year), 5.73% switched twice (0.88% in the first 6 months,1.76% in the first year) and 2 patients (0.88%) switched 3 times after the first year of treatment. 14 serious adverse events were reported leading to discontinuation of the treatment, 6 in the first 6 months and 8 in the first year of treatment. There were no reported deaths. The one-year treatment retention with biological agents was 91%. Conclusions JIA patients treated with biologics and registered in Reuma.pt showed a good profile of effectiveness and safety at 1 year. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3142

PReS-FINAL-2021: JADAS-CRP instead of JADAS-ESR...results from REUMA.PT

Recently, Juvenile Arthritis Disease Activity Score (JADAS) was found to be a valid instrument for assessment of disease activity. JADAS was developed with erythrocyte sedimentation rate (ESR) because C-reactive protein (CRP) values were not available in all databases used to validate the tool. Nordal et al compared recently in a Nordic population the JADAS based on CRP with JADAS based on ESR and concluded that these instruments correlated closely, indicating that both scores can be recommended for assessing disease activity in JIA.