José Alberto Pereira da Silva

Treating Rheumatoid Arthritis to Target : multinational recommendations assessment questionnaire.

Aim To measure the level of agreement and application of 10 international recommendations for treating rheumatoid arthritis (RA) to a target of remission/low disease activity. Methods A 10-point Likert scale (1=fully disagree, 10=fully agree) measured the level of agreement with each of 10 recommendations. A 4-point Likert scale (never, not very often, very often, always) assessed the degree to which each recommendation was being applied in current daily practice. If respondents answered ‘never’ or ‘not very often’, they were asked whether they would change their practice according to the particular recommendation. Results A total of 1901 physicians representing 34 countries participated. Both agreement with and application of recommendations was high. With regard to application of recommendations in daily practice, the majority of responses were ‘always’ and ‘very often’. A significant percentage of participants who were currently not applying these recommendations in clinical practice were willing to change their practice according to the recommendations. Conclusion The results of this survey demonstrated great support of ‘Treating RA to Target’ recommendations among the international rheumatology community. Additional efforts may be needed to encourage application of the recommendations among certain clinicians who are resistant to changing their practice.

BAFF and TACI Gene Expression Are Increased in Patients with Untreated Very Early Rheumatoid Arthritis

Objective. B cells play important roles in rheumatoid arthritis (RA). Given the beneficial effect of B cell depletion therapy in RA as well as the observed alterations in B cell subpopulations in this disease, we evaluated whether changes in the expression of genes related to B cell survival and activation were already present in patients with untreated very early RA (VERA; < 6 weeks of disease duration). Methods. The expression of a group of B cell-related activation and survival genes was quantified in peripheral blood mononuclear cells from patients with VERA by real-time PCR and compared with untreated early RA (< 1 year), established treated RA, and other untreated early arthritis conditions. Serum B cell-activating factor belonging to the tumor necrosis factor family (BAFF) was quantified by ELISA. Results. BAFF gene expression and serum levels were highest in patients with VERA. The expression of BAFF receptor (BAFF-R) increased with disease progression, while transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) was elevated since the first weeks of RA onset. Paired box 5 gene expression was also increased at all RA stages. Chemokine (C-X-C motif) receptor 5 was elevated only in established RA. No differences were observed in B cell maturation antigen, activation-induced cytidine deaminase, B lymphocyte-induced maturation protein, and B cell lymphoma 2 expression. Conclusion. Disturbances in the expression of B cell-related activation and survival genes, particularly BAFF and TACI, occur from the onset of RA and precede changes in BAFF-R. These alterations can lead to the development of autoreactive B cells from the first weeks of RA onset.

Ankylosing spondylitis susceptibility and severity - contribution of TNF gene promoter polymorphisms at positions -238 and -308.

Ankylosing spondylitis (AS) is a chronic inflammatory disease in which genetic factors play a central role. The efficacy of TNF blockers has reoriented research in this field in order to explain the influence of TNF in AS pathogenesis. The objective of this study was to access the influence of single nucleotide polymorphisms (SNPs) at positions –308 and –238 of the promoter region of TNF gene on AS susceptibility and prognosis. SNPs were determined by restriction fragment length polymorphisms in patients and controls. AS patients exhibited a decreased frequency of the A allele at position –238 (10%) when compared with controls (18%), suggesting that this could be a protective factor for disease susceptibility. In addition, the –308 GA/AA genotypes were associated with later disease onset in AS patients. These results suggest that TNF gene promoter polymorphisms at positions –238 and –308 could have a small influence on AS susceptibility and prognosis.

Treating Rheumatoid Arthritis to Target

Aim To measure the level of agreement and application of 10 international recommendations for treating rheumatoid arthritis (RA) to a target of remission/low disease activity. Methods A 10-point Likert scale (1=fully disagree, 10=fully agree) measured the level of agreement with each of 10 recommendations. A 4-point Likert scale (never, not very often, very often, always) assessed the degree to which each recommendation was being applied in current daily practice. If respondents answered ‘never’ or ‘not very often’, they were asked whether they would change their practice according to the particular recommendation. Results A total of 1901 physicians representing 34 countries participated. Both agreement with and application of recommendations was high. With regard to application of recommendations in daily practice, the majority of responses were ‘always’ and ‘very often’. A significant percentage of participants who were currently not applying these recommendations in clinical practice were willing to change their practice according to the recommendations. Conclusion The results of this survey demonstrated great support of ‘Treating RA to Target’ recommendations among the international rheumatology community. Additional efforts may be needed to encourage application of the recommendations among certain clinicians who are resistant to changing their practice.

Pachydermodactyly in a 16-Year-Old Adolescent Boy

Pachydermodactyly is a superficial benign fibromatosis of unknown etiology; it is rare, more frequent in adolescent males, and characterized by painless swelling of the proximal interphalangeal joints(PIP) of the hands. Histologic examination of the skin shows epidermal hyperplasia and increased number of dermal fibroblasts and collagen fibers.We report the case of a 16-year-old adolescent boy who presented swelling of the lateral and dorsal regions of all the metacarpophalangeal and PIP joints of the left hand and PIP and metacarpophalangeal joints of the second and fifth fingers of the right hand, with 3 years of evolution and no arthritis or functional impairment. Results of complementary diagnostic examinations were normal, with the exception of hand ultra sound that showed skin thickening, without synovial proliferation or joint effusion. Skin biopsy confirmed pachydermodactyly. The patient under went aesthetic surgery with good outcome, without recurrence.This rare condition should be distinguished from idiopathic juvenile arthritis and other entities such as knuckle pads syndrome.

Parry-Romberg syndrome in an 11-year-old female with neurological manifestations without brain imaging abnormalities

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 25 fevrier 2012

A10.5 Comparative Effectiveness of Biological Therapies in Rheumatoid Arthritis is Influenced by Response Measures and Disease Activity State

Background and Objectives Several biological therapies have become available in the last years in the management of rheumatoid arthritis (RA). Two of the most common drug classes include anti-tumour necrosis factor (TNF) and anti-interleukin-6 (IL-6) agents, which target central cytokines in the disease pathway. We have previously shown that the proportion of patients achieving remission was higher in the tocilizumab group, an anti-IL-6 agent, compared to anti-TNF therapies, but the magnitude of the effect was associated with the disease activity measure used, namely DAS28, CDAI or SDAI. The aim of this study is to assess whether this difference remains significant in other RA disease activity states. Materials and Methods We included biologic-naïve RA patients registered in the Rheumatic Diseases Portuguese Register, Reuma.pt, who have started therapy with anti-TNF (adalimumab, infliximab, golimumab) and anti-IL-6 (tocilizumab) monoclonal antibodies after 1st January 2008. Our primary outcome was the proportion of patients in each disease activity state (remission, low, moderate, high) at 6 months, applying DAS28, CDAI and SDAI. Univariate and multivariate logistic regressions were performed to compare the groups. Results 220 RA patients were enrolled, 180 treated with anti-TNF monoclonal antibodies and 40 treated with tocilizumab. Both groups had similar baseline characteristics but tocilizumab-treated patients had significantly higher SJC, DAS28, SDAI and CDAI as well as shorter disease duration. At 6 months, a significantly higher proportion of patients in the tocilizumab group had reached the DAS28 (n = 21, OR 0.16, p < 0.0001, 95%CI 0.06–0.38) and SDAI (n = 9, OR 0.29, p = 0.03, 95%CI 0.09–0.91) remission thresholds, but no significant difference was seen for CDAI (n = 8, OR 0.41, p = 0.12), in the adjusted logistic multivariate model. Moreover, the proportion of patients with moderate (n = 85, OR 3.49, p = 0.006, 95%CI 1.44–8.43) and high disease activity (n = 30, OR 6.13, p = 0.028, 95%CI 1.32–30.89) was higher in the anti-TNF group only according to DAS28. No differences were seen in the low disease activity class. Conclusions Globally, tocilizumab-treated patients had better disease activity outcomes, but the magnitude of the effect was dependent on the disease activity measure used, confirming our previous results and underlining the pronounced reduction of inflammatory markers such as ESR and CRP, translated by lower DAS28 and SDAI, respectively. Furthermore, this effect was also related to the disease activity state considered. This may be explained by the fact that these different indexes distinctly weigh the different components and/or do not classify the same patients in the same disease activity state.

BAFF AND TACI mRNA expression are increased in very early rheumatoid arthritis patients

Background B cells play several important roles in rheumatoid arthritis (RA). Previous studies by our group have demonstrated that very early rheumatoid arthritis (VERA) patients have disturbances in peripheral blood memory B cells and increased circulating B cell related cytokines. Objectives The main goal of this work was to analyse the expression of genes related with B cell survival and activation in VERA (<6 weeks of disease duration) and compare with early RA (<1 year, ERA), established RA patients (RA) and other early arthritis conditions (VEA) to identify differences between disease stages. Materials and methods BAFF, BAFF-R, TACI, BCMA, AID, CXCR5, Pax5, Blimp-1, β2m and Bcl-2 mRNA levels from peripheral blood mononuclear cell (PBMC) were determined by real-time PCR. Serum BAFF was quantified by ELISA. Results VERA patients had increased BAFF and TACI mRNA levels in comparison with controls. Moreover, BAFF mRNA expression was higher in VERA in comparison with RA and VEA patients. BAFF-R expression was elevated in ERA and RA when compared to controls. Pax5 expression was increased in all RA patients and reduced in VEA in comparison with VERA. β2m levels were elevated in VERA, ERA and VEA patients when compared to controls. No differences were observed in BCMA, AID, CXCR5, Blimp-1 and Bcl-2 expression. Furthermore, VERA patients had the highest serum BAFF levels. Conclusions Disturbances in the expression of B cell related activation genes, particularly BAFF and TACI, occur since the very early phase of RA. The increased BAFF serum and mRNA levels occurring in VERA patients might indicate BAFF as a potential therapeutic target since the first weeks of RA onset.