Gene expression profiling in the synovium identifies a predictive signature of absence of response to adalimumab therapy in rheumatoid arthritis

To identify markers and mechanisms of resistance to adalimumab therapy, we studied global gene expression profiles in synovial tissue specimens obtained from severe rheumatoid arthritis (RA) patients before and after initiation of treatment

Les spondyloarthrites : nouveautés physiopathogéniques et perspectives thérapeutiques !

• La spondyloarthrite est une affection inflammatoire chronique, d’origine immunitaire, caractérisée par une atteinte du squelette (axiale et/ou périphérique), associée la plupart du temps aux manifestations extra-articulaires (cutanée, digestive, oculaire). • Ce rhumatisme, très hétérogène, peut causer des dégâts structurels et un handicap fonctionnel, entraînant une importante réduction de la qualité de vie. • Une meilleure compréhension de sa physiopathogénie a permis, grâce à la recherche translationnelle, de développer de nouvelles stratégies thérapeutiques, avec un changement substantiel dans la prise en charge de cette affection.[Spondyloarthritis: New insights in the pathophysiology and therapeutics perspectives!] • Spondyloarthritis (Spa) is a chronic immune-mediated inflammatory disease characterized by skeletal involvement (axial, an peripheral or both), at times associated with extra-articular manifestations (skin, gut, or eye) • This heterogenic rheumatic disease may cause structural and functional impairments, in addition to a decrease in patients' quality of life. • A better understanding of the disease's pathophysiology has led to new encouraging therapeutics strategies for managing this disease

Selective involvement of the choroid plexus on cerebral magnetic resonance images: a new radiological sign in patients with systemic lupus erythematosus with neurological symptoms.

The selective involvement of the choroid plexus on brain magnetic resonance (MR) images is described in 2 patients with systemic lupus erythematosus presenting with neurological symptoms. The decrease in choroid plexus abnormalities on followup MR examination paralleled the clinical recovery with glucocorticoid therapy in both patients. Our cases indicate that selective involvement of the choroid plexus should be included in the spectrum of the radiological signs for neurological lupus

FRI0268 REMISSION IN AXIAL SPONDYLOARTHRITIS: IS THERE A DIFFERENCE BETWEEN NSAIDS AND BIOLOGICS IN THE REAL LIFE?

Background: Randomized-controlled trials (RCTs) done in axial spondyloarthritis (AxSpA) patients have shown that remission in AxSpA and nonradiographic axial SpA patients treated without biologics (BIOL) occurs infrequently (Ref 1, 2). Few are known about remission rate (RR) in daily clinical practice. Objectives: Our aim was to assess the remission rate (RR) in AxSpA patients in Real life, and to compare the RR in AxSpA patients on NSAIDs to RR for those on Biologics (TNFα blockers or IL-17A blockers). Methods: This cross-sectional study reviewed clinical data from a single center (St-Luc university hospitals, UCLouvain, Brussels) from 01/2013 to 03/2019. Last visit available for clinical assessment was evaluated. Disease activity was measured using the Bath Ankylosing Spondylitis disease activity index (BASDAI), and the Ankylosing Spondylitis disease activity score (ASDAS) using the C-reactive protein. Remission was defined as BASDAI < 4 and ASDAS < 1.3. Results: Data from 551 AxSpA patients were reviewed. 353 were men (64.3%). In the entire cohort, 478 BASDAI and 317 ASDAS were recorded. The RR according to the BASDAI was 46.7% (n = 223), and 17.3% for the ASDAS (n = 55). To look for the treatment-related RR, we stratified by the treatment (NSAIDs vs Biologics). We had 285 patients on NSAIDs (177 men, 62.5%) and 266 on BIOL (176 men, 66%). 245 BASDAI were available for NSAIDs and 233 for BIOL. 110 patients on NSAIDs (44.9%) and 113 on BIOL (48.5%) were in remission for BASDAI. Regarding ASDAS (table below), data from 172 patients on NSAIDs and 144 on BIOL were available. Out of them, 27 (15.7%) and 28 (19.4%) were in remission for NSAIDs and BIOL respectively. Chi-square test: p = 0.853

Oral pamidronate prevents high-dose glucocorticoid-induced lumbar spine bone loss in premenopausal connective tissue disease (mainly lupus) patients.

Glucocorticoid (GC)-induced osteoporosis contributes to chronic damage in patients suffering from connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE). In this study, performed in an highly selected cohort of premenopausal female CTD (mostly lupus) patients, given high-dose GC therapy for severe disease, we show that lumbar spine bone loss can be averted by treatment with oral disodium pamidronate combined with calcium salts and vitamin D3 supplements and not by calcium salts and vitamin D3 supplements alone. We stress the need for optimal GC-induced bone loss prevention therapy in premenopausal patients, a too often neglected issue in patients whose survival has dramatically improved over the last decades

Iatrogenic Cushing's syndrome and secondary adrenal insufficiency after a single intra-articular administration of triamcinolone acetonide in HIV-infected patients treated with ritonavir

The development of an iatrogenic Cushing's syndrome (ICS) followed by secondary adrenal failure remains an exceptional event after a single dose administration of a synthetic glucocorticoid. Medical attention has been drawn recently on the possible impact of ritonavir-based antiretroviral regimens on the systemic deleterious effects of a chronic administration of corticosteroids in HIV-infected patients. Three HIV-infected patients treated by a ritonavir-boosted protease inhibitor (PI) regimen received a single intra-articular injection of 40 mg triamcinolone acetonide in our university hospital. The three patients rapidly developed signs and symptoms of ICS followed by secondary adrenal insufficiency. Special attention must be paid when a single administration of corticosteroids has to be given in HIV-positive patients under ritonavir-boosted antiretroviral treatment, as these patients are at risk of developing early cushingoid features and a prolonged suppression of their hypothalamic-pituitary-adrenal axis

Tocilizumab and rituximab, but not adalimumab, display highly concordant molecular effects in the rheumatoid arthritis synovium

Objectives: The clinical effects of biologics in patients with rheumatoid arthritis (RA) are well known. By contrast, little is known about their molecular effects in the RA synovium, and how the administration of these agents can be tailored according to individual disease status. Here, we compared the effects of three biologics on global synovial gene expression profiles in RA patients. Methods: Previously reported high-density transcriptomic data (GeneChip HGU133 Plus 2.0 slides) were recovered, obtained in our laboratory using synovial biopsies from patients with osteoarthritis (OA, n=5), early untreated RA (n=7), Methotrexate-resistant RA patients before and 3 months after Adalimumab therapy (n=2x8), anti-TNF resistant RA patients before and 3 months after Rituximab therapy (n=2x12). In addition, new hybridizations were performed with synovial biopsies from untreated early RA patients before and 3 months following Tocilizumab therapy (n=2x12) Results: Comparison of RA and OA synovial biopsies led to the identification of 885 RA specific probe sets (535 are up-regulated and 350 are down-regulated in RA synovial tissue). Most (88%) of the probe sets up-regulated in the early RA synovium are down-regulated by Tocilizumab and Rituximab in their respective patients' populations; conversely, 60% of the transcripts down-regulated in RA synovial tissue are up-regulated by both therapies. Changes in gene expression induced by Tocilizumab and Rituximab are highly correlated (r = 0.5797, p < 0.0001); by contrast, much less similarities are found when Tocilizumab or Rituximab is compared to Adalimumab. When the same analyses are applied on all probe sets expressed in the synovium, the same similarities between Tocilizumab and Rituximab are found (r = 0.4116, p < 0.0001), while the effects of Adalimumab appear to be different. Conclusion: The concordance between the molecular effects of Rituximab and Tocilizumab suggests that IL-6 producing- and B cells are major players in the physiopathology of the disease. Adalimumab admisnistration is associated with different patterns of molecular changes in the RA synovium. These data contribute to a better knowledge of the synovial molecular effects of therapies and open perspectives for the individualization of therapeutic decisions