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Objective Adult-onset Still's disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment. Methods This was a retrospective open-label study of TCZ treatment in 34 patients with AOSD who had experienced an inadequate response to corticosteroids and at least 1 standard synthetic immunosuppressive drug and also, in many cases, biologic agents. Results The mean ± SD age of the patients (8 men and 26 women) was 38.7 ± 16.1 years. The median duration of AOSD before TCZ was initiated was 4.2 years (interquartile range [IQR] 1–9 years). The initial dosages of intravenous TCZ were 8 mg/kg every 4 weeks in 22 patients, 4 mg/kg every 4 weeks in 2 patients, and 8 mg/kg every 2 weeks in 10 patients. TCZ treatment resulted in rapid and maintained improvement in both clinical and laboratory parameters. After 1 year of TCZ therapy, the incidence of joint manifestations had decreased from 97.1% at baseline to 32.4%, the incidence of both cutaneous manifestations and fever had decreased from 58.8% to 5.9%, and the incidence of lymphadenopathy had decreased from 29.4% to 0%. A dramatic reduction in laboratory markers of inflammation, including the C-reactive protein level, the erythrocyte sedimentation rate, and the ferritin level, was achieved. The median dosage of prednisone was also reduced, from 13.8 mg/day (IQR 5–45) at the initiation of TCZ to 2.5 mg/day (IQR 0–30) at 12 months. After a median followup of 19 months (IQR 12–31 months), only 2 patients required permanent discontinuation of TCZ therapy because of severe infections. Conclusion TCZ treatment was associated with rapid and maintained clinical and laboratory improvement in patients with AOSD refractory to standard treatment. However, joint manifestations seem to be more refractory to treatment compared with systemic manifestations.

To assess effectiveness and safety of certolizumab PEGol (CZP) in rheumatoid arthritis (RA) patients after 12 months of treatment and to detect predictors of response.Observational longitudinal prospective study of RA patients from 35 sites in Spain. Variables (baseline, 3- and 12-month assessment): sociodemographics, previous Disease Modifying Anti-Rheumatic Drug (DMARD) and previous Biological Therapies (BT) use; TJC, SJC, ESR, CRP, DAS28, SDAI. Response variables: TJC, SJC, CRP, ESR, and steroids dose reductions, EULAR Moderate/Good Response, SDAI response and remission, DAS28 remission. Safety variables: discontinuation due to side-effects. Descriptive, comparative and Logistic regression analyses were performed.We included 168 patients: 79.2% women, mean age 54.5 years (±13.2 SD), mean disease duration 7.5 years (±7.3 SD). Mean number of prior DMARD: 1.4 (±1.2 SD), mean number of prior BT was 0.8 (±1.1). Mean time on CZP was 9.8 months (±3.4 SD). A total of 71.4% were receiving CZP at 12-month assessment. Baseline predictors of response: lower prior number DMARD; low number prior BT; higher CRP, ESR, TJC, SJC, DAS28 and SDAI (p 0.05) scores. A 25/46.4% Moderate/Good Response, a 20% SDAI remission, and a 44% DAS28 remission were observed. We observed 48 discontinuations (28.6%), 31 due to partial or complete ineffectiveness, and 17 due to side-effects.CZP showed benefit in severe RA patients, with significant reduction of all effectiveness parameters, despite the high prevalence of previous BT exposure in our series. We found CRP, ESR, prior DMARD/BT number, TJC, SJC, DAS28, and SDAI as baseline predictors of response. CZP was mostly well tolerated.

Objective.The efficacy of antibody-based biological therapies currently used in psoriatic arthritis (PsA) depends not only on their blocking effect on the targeted molecule but also on their binding affinity to genetically defined variants of cell-surface Fc-γ receptors. Our objective was to assess the potential influence of functionally relevantFCGR2A/CD32A(H131R) andFCGR3A/CD16A(V158F) genetic polymorphisms on the EULAR response to tumor necrosis factor-α (TNF-α) blocker therapy in PsA.Methods.In total 103 patients with PsA starting anti-TNF-α therapy were included. The efficacy of therapy was evaluated according to EULAR response criteria at 3 and 6 months.FCGR2A-R131H andFCGR3A-F158V polymorphisms were genotyped. Potential correlations between clinical response and theFCGR2A-R131H andFCGR3A-F158V polymorphisms were evaluated.Results.EULAR response (moderate plus good) was 85.4% at 3 months and 87.4% at 6 months, while good EULAR response was 61.2% and 62.1%, respectively. More patients with high-affinityFCGR2Agenotypes (homozygous or heterozygous combinations) achieved a EULAR response at 6 months compared to patients with the low-affinity genotype (RR; p = 0.034, adjusted comparison error rate < 0.025). This association was due mainly to the group of patients treated with etanercept. No correlation was found for theFCGR3Apolymorphism. Similarly, no effect of C-reactive protein levels was observed.Conclusion.Our data indicate thatFCGR2Apolymorphism may influence the response to TNF-α blockers (namely etanercept) in PsA in a direction opposite to that previously found in patients with rheumatoid arthritis.

Idiopathic osteoporosis is a frequent cause of osteoporosis in young premenopausal women. However, there are no data about the treatment of these patients. The aim of this study was to analyse the evolution of bone mineral density (BMD) in premenopausal women with idiopathic osteoporosis treated with a conservative approach. Retrospective study of 16 premenopausal women with idiopathic osteoporosis (aged 35.7+/-7 years) with a mean follow-up period of 3 years (1-6 years). BMD measurements at the lumbar spine and femoral neck were obtained in all patients at baseline and yearly (patients had one or more fragility fractures and/or a Z score < -2 in the lumbar spine or femur). Secondary causes of osteoporosis were excluded in all patients. Patients were treated with calcium and vitamin D to achieve a calcium intake of up to 1,500 mg/day and were advised to increase physical activity. A significant increase in lumbar and femoral BMD was observed after 2 and 3 years of follow-up, respectively (1.9+/-1.9% mean increase in lumbar spine, p= 0.021, at 2 years) (5.6+/-4.5% mean increase in femur, p=0.04, at 3 years). The serum total alkaline phosphatase (TAP) values increased at 2 years (122+/-46 vs 140+/-36 U/l, p=0.054). In addition, a negative correlation between baseline TAP serum values and lumbar BMD evolution at 2 years was observed (r=-0.748, p=0.013). No patient developed new skeletal fractures during the follow-up period. In young premenopausal women with idiopathic osteoporosis the conservative treatment with supplements of calcium and vitamin D associated with an increase of physical activity is associated with an increase in BMD without evidence of further skeletal fractures after more than 3 years of follow-up.

To assess the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) patients with refractory disease and/or with unacceptable side effects due to corticosteroids.A retrospective multicenter open-label study on 22 GCA patients treated with TCZ at standard dose of 8mg/kg/month. The main outcomes were achievement of disease remission and reduction of corticosteroid dose.The mean age ± standard deviation of patients was 69 ± 8 years. The main clinical features at TCZ onset were polymyalgia rheumatica (n = 16), asthenia (n = 7), headache (n =5), constitutional symptoms (n = 4), jaw claudication (n = 2), and visual loss (n = 2). Besides corticosteroids and before TCZ onset, 19 of 22 patients had also received several conventional immunosuppressive and/or biologic drugs. Of 22 patients, 19 achieved rapid and maintained clinical improvement following TCZ therapy. Also, after a median follow-up of 9 (interquartile range: 6-19) months, the C-reactive protein level had fallen from 1.9 (1.2-5.4) to 0.2 (0.1-0.9)mg/dL (p0.0001) and the erythrocyte sedimentation rate decreased from 44 (20-81) to 12 (2-20)mm/1st hour (p = 0.001). The median dose of prednisone was also tapered from 18.75 (10-45) to 5 (2.5-10)mg/day (p0.0001). However, TCZ had to be discontinued in 3 patients due to severe neutropenia, recurrent pneumonia, and cytomegalovirus infection. Moreover, 1 patient died after the second infusion of TCZ due to a stroke in the setting of an infectious endocarditis.TCZ therapy leads to rapid and maintained improvement in patients with refractory GCA and/or with unacceptable side effects related to corticosteroids. However, the risk of infection should be kept in mind when using this drug in patients with GCA.

Secondary amyloidosis is an unusual complication of systemic lupus erythematosus (SLE). We report the case of a 60-year-old woman with SLE and secondary amyloidosis who developed class III proliferative lupus nephritis 13 years after the onset of amyloid nephropathy. The patient was treated with mycophenolate mofetil (1.5 g/day) with a significant improvement in proteinuria.

In a previous study, we found that synovial immunopathology differs between Behcet disease (BD) and psoriatic arthritis (PsA). The objective of this study is to describe the macroscopic features of early untreated knee synovitis in BD and PsA. Fourteen consecutive patients with active early knee synovitis (seven BD and seven PsA) undergoing rheumatologic arthroscopy were assessed. The following macroscopic synovial features were evaluated and scored by analyzing the video recordings of each procedure: capillary hyperaemia, morphology of synovitis, vascular pattern, fibrinoid membranes, and topographic distribution of these features. Video-recording of 35 early untreated arthritis patients with different diagnoses were also studied looking for BD-like macroscopic features. Six out of seven BD patients had extensive fibrinoid membranes and large areas of erythematous synovitis without villi or a distinctive vascular pattern, while PsA patients had diffuse erythematous villous synovitis with a tortuous vascular morphology. None of the 35 patients with early untreated arthritis exhibited all the characteristic features of BD synovitis. This exploratory study shows some distinctive features between BD and PsA knee synovitis that confirm macroscopic differences in patients with previously reported immunopathological differences.

Objective: Fcγ receptor (FcγR) polymorphism influences the affinity of the receptor for Ig, which may, in turn, affect the efficacy of Ig-based therapies. The relationship between functional single nucleotide polymorphisms (SNP) of the FCGR2A and FCGR3A genes and the response to anti-tumour necrosis factor (TNF)α therapy (infliximab) in patients with rheumatoid arthritis (RA) was assessed. Methods: A total of 91 patients with RA (89% female; 76.7% rheumatoid factor (RF) positive) starting therapy with infliximab were evaluated at 0, 6 and 30 weeks using the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and the 28-joint Disease Activity Score (DAS28) was evaluated using three parameters, including C-reactive protein (CRP) (DAS28 3v-CRP) changes during the follow-up. Genotyping of FCGR2A -R131H and FCGR3A -F158V polymorphisms was performed by allele-specific PCR and PCR sequence-based typing, respectively. The χ 2 and Fisher exact tests were used to show differences in the outcome variables, and analysis of variance (ANOVA) to analyse the evolution of DAS28 3v-CRP. A generalised linear models multivariable analysis was also performed. Results: At week 6 of follow-up, the proportion of patients achieving 50% improvement as per ACR criteria (ACR50) and EULAR good responses were significantly higher among homozygotes of the low affinity FCGR3A allele (FF: 24.1% and VV-VF:2.2%; p = 0.003 and FF: 44.8% and VV-VF: 22.9%; p = 0.040, respectively). At week 30, homozygotes of the low affinity FCGR2A allele had a better ACR20 response (RR: 60% and HH-RH: 33.3%; p = 0.035). Changes in DAS28 3v-CRP during follow-up were consistent with those observed in ACR and EULAR responses. Conclusions: The response to anti-TNFα treatment with infliximab in patients with RA is influenced by the FCGR2A and FCGR3A genotypes. This effect is observed at different times in the follow-up (6 and 30 weeks, respectively) indicating the dynamic nature of the FcγR versus Ig interaction.

Objective:To investigate the clinical significance of lymphoid neogenesis (LN) in rheumatoid arthritis (RA), the clinicopathological correlates of this process and its evolution after anti-tumour necrosis factor (TNF)α therapy in a large series of synovial tissues were analysed.Methods:Arthroscopic synovial biopsies from 86 patients with RA were analysed by immunohistochemistry. LN was defined as the presence of large aggregates of lymphocytes with T/B cell compartmentalisation and peripheral node addressin (PNAd) positive high endothelial venules. Clinical variables at baseline and after prospective follow-up were compared in LN positive and negative RA subsets. The evolution of LN and its correlation with the clinical course in a subgroup of 24 patients that underwent a second arthroscopic biopsy after anti-TNFα therapy was also analysed.Results:LN was present in 49% of RA synovial tissues. Patients with LN had a significantly higher disease duration and a higher previous use of anti-TNFα agents. During prospective follow-up, the proportion of patients achieving good or moderate European League Against Rheumatism (EULAR) 28-joint Disease Activity Score (DAS28) responses was significantly lower in patients who were LN positive despite a significantly higher use of anti-TNFα agents. By multivariate logistic regression analysis, LN remained as an independent negative predictor of response to therapy. In the subgroup of patients rebiopsied after anti-TNFα therapy, reversal of LN features occurred in 56% of the patients and correlated with good clinical responses.Conclusions:Synovial LN in RA predicts a lower response to therapy. LN features can be reversed after a short period of anti-TNFα therapy in parallel to good clinical responses.

Chagas' disease is an endemic parasitic disease and constitutes an important health problem in Latin American countries. The increasing number of immigrants from these countries has resulted in a rise in diagnosis and consequently in the treatment of this disease in developed countries not familiar with this condition. Currently, benznidazole is used for treatment of this condition. However, undesirable effects have been reported with this treatment, and there are few data about continuous long-term use of this drug. We describe a case of invalidating pain syndrome in a 31-year-old Bolivian woman with Chagas' disease while receiving benznidazole therapy. Because of the number of cases with this condition will probably increase because of immigration, a better understanding of the side effects of the treatment of this disease is essential.

Objective To analyze the clinical efficacy of anti-tumor necrosis factor (TNF)-α therapy in the SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. We describe 2 new cases with ilium osteitis as the main SAPHO syndrome feature and review reported cases treated with anti-TNF-α. Methods A literature search of SAPHO syndrome cases treated with TNF-α blocking therapy with special emphasis on osteoarticular and skin responses was performed. Results Eighteen cases were identified: 17 SAPHO syndrome and 1 chronic recurrent multifocal osteomyelitis, a juvenile variant of SAPHO syndrome. Sixteen were reported cases and 2 were nonreported cases seen in our arthritis unit. Sixteen patients received infliximab and 2 received etanercept, with an early, sustained clinical improvement in most cases. Conclusions Anti-TNF-α therapies are effective treatment for patients with refractory SAPHO syndrome, not only for cutaneous lesions but also for persistent bone lesions such as osteitis.

Background Non-infectious aortitis is often refractory to standard immunosuppressive therapy. IL-6 has been implicated in the pathogenesis of aortitis. Objectives Our aim was to assess the efficacy of the anti-IL6 receptor monoconal antibody tocilizumab (TCZ) in a series of patients with refractory non-infectious aortitis. Methods We reviewed 16 patients (14 women/2 men) with refractory aortitis diagnosed by imaging (CT angiography, MR angiography, and/or PET) that were treated with TCZ. Results The mean age ± SD was 51.4±20.1 years. The underlying conditions were: Takayasu arteritis (TakA) (N=7 cases), giant cell arteritis (GCA) (n=7), relapsing polychondritis (RP) (n=1), and aortitis associated with retroperitoneal fibrosis (n=1). TCZ was the first biologic drug used in all patients with GCA, and in the patient with aortitis associated with retroperitoneal fibrosis but in only 2 of 7 TakA patients. In the remaining cases anti-TNF inhibitors were prescribed before TCZ (standard dose was 8 mg/kg/iv/4 weeks). After a mean ± SD follow-up of 11.8±6.6 months most patients experienced clinical improvement, showing reduction of erythrocyte sedimentation rate from 43±36 mm/1st h to 5±4 mm/1st h at last visit. At TCZ onset, 25% of patients had fever and 19% polymyalgia rheumatica. These manifestations disappeared after 3 months of TCZ therapy. A corticosteroid sparing effect was also achieved (from 27.3±17.6 mg/day of prednisone at TCZ onset to 4.2±3.8 mg/day at last visit). TCZ had to be discontinued in a patient because of severe neutropenia. Conclusions TCZ appears to be effective and relatively safe in patients with inflammatory aortitis refractory to corticosteroids or to other biologic immunosuppressive drugs. Acknowledgements This study was supported by a grant from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2984

Background Aortitis is the inflammation of the aortic wall, regardless of the underlying condition. It can occur alone or associated with other causes. Aortitis is often refractory to standard immunosuppressive therapy. Objectives To assess the efficacy and side-effects of biological therapy in patients with inflammatory aortitis. Methods Multicenter study of 30 patients diagnosed of inflammatory aortitis due to different underlying conditions. The diagnosis of aortitis was based on imaging (CT angiography, MR angiography, PET or echocardiogram). Results We studied 30 patients (27women/3men); mean age±SD, 47.07±18.62 years. The underlying etiologies were: Takayasu arteritis (TKY) (16 cases), giant cell arteritis (GCA) (7), relapsing polychondritis (2), sarcoidosis (1), ulcerative colitis (1), Sjogren’s syndrome (1), Behcet’s syndrome (1) and idiopathic aortitis (1) (Table). In 3 of 30 patients, biological therapy had to be discontinued: 1 GCA with tocilizumab (TCZ) because of neutropenia, 1 GCA with infliximab (IFX) for infusional reactions and 1 TKY with IFX for recurrent pneumonia. Of the remaining 27 patients undergoing biologic therapy, 13 were receiving TCZ (6 TKY, 5 GCA, 1 relapsing polychondritis and 1 idiopathic aortitis), 11 IFX (7 TKY, 2 GCA, 1 Behcet’s syndrome, and 1 relapsing polychondritis), 2 were receiving etanercept (2 TKY), 2 rituximab (1 TKY and 1 Sjogren’s syndrome) and 2 adalimumab therapy (1 ulcerative colitis and 1 sarcoidosis). Switching from a biologic therapy to another occurred in 8 cases. It was due to inefficacy in 7 cases and allergic reaction in 1 case. After a median [interquartile 25-75] follow-up of 16 [11-24] months most patients experienced clinical improvement and a reduction of ESR levels (from 42.6±29.4 mm/1st h to 14.8±14.6 mm/1st h). This fact made possible a reduction in the dose of corticosteroids (prednisone: 25.8±20.5 mg/day to 4.6±3.9 mg/day). Conclusions Our results indicate that biological therapy seems to be an effective and safe therapeutic option in inflammatory aortitis refractory to conventional immunosuppressive therapy. Disclosure of Interest None Declared