Background: B-cells play a major role in the pathogenesis and perpetuation of the immune response in systemic lupus erythematosus (SLE). So far, B-cell subtypes have been studied well, but the precise mechanisms of the B-cell alterations during disease activity and during remission, depending on different medication, are still unclear. Objectives: The aim of our study was to investigate the drug dependent alterations in the B-cell repertoire of SLE patients with low disease activity (SLEDAI – 2K ≤4). Methods: Peripheral blood samples from 39 patients suffering from SLE (mean±SD; age 43±13 years, 87.2% females, disease duration 11.1±7 years) were drawn over 2 years. All SLE patients were in remission or low disease activity (median±SE, SLEDAI of 2.0±1.5). B-cells were characterized using CD19, CD20, CD5, CD27 antibodies and were grouped in naïve (IgD + 27 - ), non-switched memory (IgD + , CD27 + ), memory (IgD -, CD27 + ), B1 (CD5 + 27 - ) and MBL-like (CD5 ++ ) B-cells. A quantitative flow cytometric bead-based assay (QuantiBRITE PE kit from Becton Dickinson) was used for the estimation of CD19 antibodies bound per cell. Further, CD38 and CD86 antibodies were used to characterize the B-cell subsets. All cytometric measurements were performed using a standardized BD LSR Fortessa platform. After 3 years of follow-up, patients’ data about disease activity and current medication were obtained. Results: 22 SLE patients were treated with hydroxychloroquine (85.8%) and 19 patients received mycophenolate mofetil (MMF; n=14; 54.6%) or azathioprine (AZA; n= 5; 19.5 %). 5 patients were treated with other DMARDs. Independently of hydroxychloroquine and/or MMF, no significant differences were seen in naïve, non-switched memory, post-switched memory, plasma blasts, B1- or MBL-like B-cells. Patients treated with AZA had significantly lower naïve B-cells (mean±SD, 39.3±6.7vs. 73.1±19.3 %; p = 0.028), but had significantly higher IgD-post switched B-cells (31.2±9.1 vs.12.5 ±9.2 %; p = 0.028, respectively) compared with no AZA-treatment. Interestingly, activated B-cells (5.5±1.5 vs. 1.8±1.1%; p = 0.009) were significantly higher in AZA-treated. After 3 years of follow-up, almost all patients were in remission (median±SE, SLEDAI of 2.0±2.0), except of 3 patients with a SLEDAI of ≥ 6. Interestingly, those patients had at baseline, statistically higher naïve B-cells (p = 0.041) and lower B1-like B-cells (p =0.020) compared with patients with low disease activity. Conclusion: Our results suggest that independently of hydroxychloroquine and/or MMF treatment, all patients with low disease activity had similar normal B-cell subsets. Interestingly, in the small group of patients who were treated with AZA, a reduced regeneration of B-cells was shown. Patients with higher disease and high naïve B-cells showed an increased disease activity after three years. Acknowledgments: The research was performed in “CBmed” and funded by the Austrian Federal Government within the COMET K1 Centre Program, Land Steiermark and Land Wien. Disclosure of Interests: None declared
Background: Tender and Swollen Joint Counts (TJC, SJC) are items of disease activity scores in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Recent studies suggest that TJC do not adequately reflect ongoing inflammation in RA when using Ultrasound (US) as a reference standard, and that pain might be due to other, non-inflammatory causes. 1, 2 In PsA, the role of tenderness and swelling of joints for reflecting active inflammation has not been well studied so far. Objectives: To evaluate tender (TJ) and swollen joints (SJ) for the assessment of inflammation in PsA. Methods: We performed a prospective study on 83 PsA patients undergoing clinical and ultrasound examinations at two study visits scheduled 12 months apart. Tenderness and swelling were assessed for 68 and 66 joints respectively and US examinations, including grey scale (GS) and power doppler (PD) were conducted at all 68 joints. GS- (range 0-204) und PD sum scores (0-204) were calculated. At patient level, correlations were performed between TJC, SJC and clinical or US values. At joint level a GS value≥1 and/or PD value≥1 was defined as active synovitis, which was compared to whether a joint was tender, swollen or both. A generalized linear mixed model was created to assess the predictive value of TJ and SJ for active synovitis after 12 months, taking into consideration the joint site. Results: At baseline the median TJC and SJC for 83 patients was 4 (range 0-59) and 1 (0-20), respectively and the median GSS- and PD sum score was 16 (3-56) and 3 (0-31) respectively. SJC correlated with the GSS sum score (r= 0.37, p=0.004) and PD sum score (r =0.47, p<0.001), while TJC only correlated with PD sum score (r=0.33, p=0.01). TJC correlated better than SJC with patient reported outcomes like patient global assessment (TJC: r=0.57, p<0.001; SJC r=0.39, p=0.002) and health assessment questionnaire (TJC: r=0.50, p<0.001, SJC no significant correlation). Swollen joints (with or without tenderness) showed active synovitis (GSS≥1 and/or PD≥1) in 67.6% of cases, while tender joints (with or without swelling) showed signs of US activation in only 34.5%. A joint that was considered swollen at baseline was more likely to express active synovitis after 12 months (OR: 4.3, 97.5 CI: 2.9-6.2), compared to a joint that was either tender or swollen at baseline (OR: 2.8, 97.5 CI: 2.1-3.5). Conclusion: SJC are more closely linked with US signs of inflammation as compared to TJC in PsA. While swelling of a joint predicts US inflammation after a year, the information whether the joint is additionally tender or not, gives no additional predictive information. References: [1]Hammer HB, Michelsen B, Sexton J, et al. Swollen, but not tender joints, are independently associated with ultrasound synovitis: results from a longitudinal observational study of patients with established rheumatoid arthritis. Ann Rheum Dis 2019;78:1179-85. [2]Hammer HB, Michelsen B, Provan SA, et al. Tender joint count may not reflect inflammatory activity in established rheumatoid arthritis patients - results from a longitudinal study. Arthritis Care Res (Hoboken ) 2018 Disclosure of Interests: None declared
Background:Under physiological conditions, T regulatory cells (Tregs) are responsible for the downregulation of the immune response. In autoimmune diseases, such as rheumatoid arthritis (RA), auto-inflammation is driven by an imbalance of activation and downregulation of immunological pathways. Thus, treatment plans for autoimmune diseases often involve the enhancement of immunoregulatory pathways by administering inhibitors of costimulation, i.e. CTLA-4-Ig (abatacept, ABA). ABA binds specifically to CD80 and CD86 on antigen presenting cells (APC). Consequently, T cell activation via the CD28 receptor is blocked. Previous studies have demonstrated surprising effects of abatacept on Tregs, specifically decreased frequency of these cells but enhancement in their function1. Whether these alterations can only be found in patients with ABA treatment, or whether they are also present in patients receiving other anti-inflammatory drugs is currently unknown.Objectives:The aim of our research was to delineate the impact of ABA on the different subsets of effector and regulatory T cells in RA and compare these findings with patients receiving tocilizumab (TCZ) or rituximab (RTX).Methods:Peripheral blood samples from 56 RA patients (median ± SE; age: 60.5 ± 1.3 years, female ratio: 0.7, disease duration: 17.9 ± 2.1 years; respectively) were drawn over a sampling period of 2 years. Freshly isolated PBMCs of RA patients were stained with fluorochrome-labelled antibodies and T cell subsets were identified by flow cytometric means. CD3+CD4+T cells were further classified using different T cell markers (CD25, CD127, CD39, CD95). All cytometric measurements were performed using a standardized BD LSR-Fortessa platform. RA patients were compared according to their treatment with ABA, TCZ or RTX.Results:Eighteen out of 56 RA patients (32%) received ABA, 25 patients (45%) received TCZ and 13 patients (23%) were under CD20+ cell depletion therapy with RTX. RA patients receiving ABA displayed a significant decrease in CD3+CD4+CD25+CD127dimTregs (3.7% ± 0.4) compared to patients with TCZ (5.4% ± 0.4, p = 0.041) and patients under RTX treatment (7.52% ± 0.93, p = 0.026). CD39+Tregs were significantly higher in RA patients treated with TCZ (49.5% + 3.2, p = 0.000) or RTX (50.5% ± 5.3, p = 0.026) compared to patients receiving ABA (24.5% ± 3.1). In addition, the frequency of CD95+Tregs was significantly reduced in ABA patients compared to RTX patients (59.6% ± 3.1 vs.76.7% ± 3.6, p = 0.014; respectively). Interestingly, T cells displaying an effector T cell phenotype (CD3+CD4+CD25+/-CD127+) were increased in ABA treated patients compared to RTX treated patients (59.6% ± 3.1 and 76.7% ± 3.6, p = 0.002). Since none of our patients were a non-responder or had high disease activity, we could not analyse whether these changes are associated with treatment outcome.Conclusion:Our data demonstrate that blockage of T cell stimulation via ABA leads to characteristic alterations in different regulatory and effector T cells not seen in patients treated with TCZ or RTX. Further studies must clarify whether the analysis of regulatory and effector T cell subpopulations before treatment initiation can be used as biomarker for treatment response.References:[1]Álvarez-Quiroga C, Abud-Mendoza C, Doníz-Padilla L, et al. CTLA-4-Ig therapy diminishes the frequency but enhances the function of treg cells in patients with rheumatoid arthritis.J Clin Immunol. 2011;31(4):588-595.doi:10.1007/s10875-011-9527-5Acknowledgments:Work done in “CBmed” was funded by the Austrian Federal Government within the COMET K1 Centre Program, Land Steiermark and Land Wien.Disclosure of Interests:None declared
Background The increasing armamentarium of disease-modifying therapies in multiple sclerosis is accompanied by potentially severe adverse effects. The cell-adhesion molecule CD62L, which facilitates leukocyte extravasation, has been proposed as a predictive marker for treatment tolerability. However, pre-analytical procedures might impact test results, thereby limiting its clinical usability. Whether the immediate analysis of CD62L expression of peripheral blood mononuclear cells can aid treatment decision making is yet unclear. Objective To investigate the effect of various disease-modifying therapies in multiple sclerosis on CD62L expression of CD3 + CD4 + peripheral blood mononuclear cells in freshly collected blood samples. Methods We collected peripheral blood samples from patients with clinically isolated syndrome and multiple sclerosis (baseline/follow up n = 234/ n = 98) and healthy controls ( n = 51). CD62L + CD3 + CD4 + expression was analysed within 1 hour by fluorescence-activated cell sorting. Results CD62L + CD3 + CD4 + expression was significantly decreased in patients treated with natalizumab ( n = 26) and fingolimod ( n = 20) and increased with dimethyl-fumarate ( n = 15) compared to patients receiving interferon/glatiramer acetate ( n = 90/30) or no disease-modifying therapies ( n = 53) and controls ( n = 51) ( p<0.001). CD62L expression showed temporal stability during unchanged disease-modifying therapy usage, but increased after natalizumab withdrawal and decreased upon fingolimod introduction. Conclusion CD62L + CD3 + CD4 + expression is altered in patients treated with different disease-modifying therapies when measured in freshly collected samples. The clinical meaning of CD62L changes under disease-modifying therapies warrants further investigation.
Background Cut offs for low disease activity (LDA) using psoriatic arthritis (PsA) specific composite scores have recently been proposed.1–3 Whether these definitions adequately reflect the absence of inflammation is unknown. Objectives To evaluate these definitions against a low level of activity according to ultrasound examination. Methods We performed a prospective study on 83 PsA patients undergoing clinical and ultrasound examinations at two study visits scheduled 6 months apart. LDA was assessed using the Disease Activity index for Psoriatic Arthritis (DAPSA≤14), the Psoriatic ArthritiS Disease Activity Score (PASDAS ≤3.2), the Composite Psoriatic Disease Activity Index (CPDAI≤4), the Disease Activity Score 28 CRP (DAS28-CRP≤2.8) and the Minimal Disease Activity criteria (MDA). Ultrasound (US) evaluation was performed at 68 joints (evaluating synovia, peritendinous tissue, tendons and bony changes) and 14 entheses. Minimal ultrasound disease activity (MUDA) was defined as a Power Doppler (PD) score ≤1, respectively at joints, peritendinous tissue, tendons and entheses. Results LDA was present in 33.7%–65.0% of patients at baseline and in 44.3%–80.6% at follow-up examination, depending on the criteria used. MUDA was observed in 16.9% at baseline and in 30% at follow-up. At baseline only the DAPSA-LDA definition was useful to identify MUDA patients (78.6% of patients identified correctly), whereas at follow up >80% of MUDA patients were correctly classified as LDA according to DAPSA, PASDAS, CPDAI and DAS28-CRP. Only DAPSA (Sensitivity (S)=88.2%, Specificity (Sp)=40.5, p=0.033), PASDAS (S=88.2%, Sp=55.0%, p=0.002) and the MDA criteria (S=71.4%, Sp=67.3%, p=0.003) were able to discriminate patients with and without MUDA at follow-up. A global ultrasound inflammation subscore for joints and entheses (GUIS-j/e), containing the above mentioned US variables, was significantly higher in patients with active disease versus patients in LDA according to DAPSA (p=0.002) and PASDAS (p=0.013) at baseline and DAPSA (p=0.007), PASDAS (p=0.001), CPDAI (p=0.021) and the MDA criteria (p<0.001) at follow up. Conclusions Of all tested LDA definitions, DAPSA was overall the most efficacious in differentiating between high and low ultrasound scores and better identified patients with MUDA as compared to the other tested scores. References [1] Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: A proposed objective target for treatment. Annals of the Rheumatic Diseases69(1):48–53. [2] Helliwell PS, FitzGerald O, Fransen J. Composite disease activity and responder indices for psoriatic arthritis: A report from the GRAPPA 2013 meeting on development of cutoffs for both disease activity states and response. The Journal of Rheumatology2014;41(6):1212–7. [3] Schoels MM, Aletaha D, Alasti F, Smolen JS. Disease activity in Psoriatic Arthritis (PsA): Defining remission and treatment success using the DAPSA score. Ann Rheum Dis2016;75(5):811–8. Disclosure of Interest None declared
Background Patients with primary Sjögren Syndrome (PSS) are affected by glandular and extraglandular manifestations leading to physical and psychological impairment. To what extent these factors affect the health related quality of life (HRQL) of these patients is largely unexplored. Disease activity scores for PSS have been developed but there is no disease-specific HRQL questionnaire available so far. Objectives To develop a questionnaire for the assessment of HRQL in PSS. Methods In a previous qualitative study, concepts related to HRQL in PSS were identified by focus-group interviews with PSS patients. Based on these concepts, a questionnaire (PSS-QoL) was developed focusing on two main topics: physical (pain and dryness) and psychosocial dimension. The first draft of this questionnaire was evaluated by semi-structured interviews with PSS patients (n=6) and rheumatologists (n=4). Based on their feedback, a revised questionnaire was constructed and re-evaluated by the patients and physicians. Subsequently, psychometric testing of PSS-QoL was performed in 75 PSS patients of the outpatient clinic of the Medical University Graz. For testing of internal consistency Crohnbach9s α was used. Convergent construct validity was tested by correlating the scores with the ESSPRI and the EQ-5D. Reliability was examined by asking patients who considered themselves to be in a stable disease to complete the questionnaire 1–2 weeks apart. In addition, an English version of PSS-QoL was was developed using a standard methodology for translation. Results Out of the 75 PSS patients, 91% were female, disease duration was 4.8±4.08 years and age of patients was 58.5±12.5 years.The internal consistency of the PSS-QoL showed a Crohnbach9s α of 0.892 and we found a moderate correlation of the PSS-QoL with the ESSPRI (Corrcoeff=0.625) and the EQ-5D (EQ5D-pain/discomfort; corrcoeff=0.531). A second assessment was performed after 1–2 weeks in 21 patients with stable disease. The ICC for PSS-QoL was 0.958 (95% CI 0.926 to 0.981). In comparison, the ICC for EQ-5D in this population was 0.854 (95% CI 0.735 to 0.933). Subsequently, the final German version of PSS-QoL was translated forward and back into English by native speakers. Conclusions A questionnaire to assess the HRQL in PSS patients has been developed and tested for its psychometric properties. The PSS-QoL should allow for a better and more comprehensive assessment on patients9 HRQL in PSS. Multicentre studies for further validation are needed. Disclosure of Interest None declared
Background Rheumatoid arthritis is a chronic form of inflammatory arthritis that is thought to have an early stage or reversibility with effective therapy (“window of opportunity”). Objectives In the present study, we explored the effects of induction therapy with anti-TNFα antibody infliximab (IFX) plus methotrexate (MTX) compared with MTX alone and with placebo (PL) in patients with very early inflammatory arthritis. Methods In an investigator-initiated, double-blind, randomized, placebo-controlled, multi-center trial, patients with synovitis of 12–16 weeks duration in at least 2 joints underwent one year of treatment with IFX in combination with MTX, MTX monotherapy or PL randomized in a 2:2:1 ratio. The primary endpoint was clinical remission after 1 year (sustained for at least two consecutive visits 8 weeks apart including week 54) with remission defined as no swollen joints, 0 - 2 tender joints and a C-reactive protein (CRP) level within the normal range (<0.5 mg/dl) or a normal ESR (<25 mm/h). Further, sustainability of remission was assessed during the second year of the study, during which patients received no treatment. The trial was registered at www.isrctn.com(ISRCTN21272423). Results See Table 1. 90 patients participated in the present study. At week 54 (primary endpoint), 32% of the patients in the IFX+MTX group achieved sustained remission compared with 14% on MTX alone and 0% on PL (Table). This difference was statistically significant for all three groups (p<0.05) and for IFX+MTX vs PL (p<0.05) separately, but not for IFX+MTX vs MTX (p=0.10), nor for MTX vs PL (p=0.31). Remission was maintained during the second year on no therapy in 75% of the IFX+MTX patients but was lost in 80% of the MTX-only-patients (Table). The analysis of radiographic progression did not reveal significant differences between the three treatment groups. The number needed to treat (NNT) to achieve one additional sustained remission at 52 weeks with IFX+MTX was 3 compared to placebo; the NNT for MTX alone versus placebo was 7 (NNT=6 for IFX+MTX vs MTX alone). Conclusions These results indicate that patients with early arthritis can benefit from induction therapy with anti-TNF plus MTX compared to MTX alone, suggesting the existence of a window of opportunity where intensive treatment can alter the disease evolution Disclosure of Interest T. Stamm Grant/research support from: For all authors: DINORA was partly funded by a grant from Janssen (previously Centocor). TS: AbbVie, Consultant for: AbbVie, Novartis, Speakers bureau: AbbVie, Janssen, MSD, Novartis and Roche, K. Machold: None declared, D. Aletaha Grant/research support from: AbbVie, Pfizer, Grünenthal, Merck Medac, UCB, Mitsubishi/Tanabe, Janssen and Roche, Consultant for: AbbVie, Pfizer, Grünenthal, Merck Medac, UCB, Mitsubishi/Tanabe, Janssen and Roche, F. Alasti: None declared, P. Lipsky Consultant for: Janssen, EMD Serono, Astra Zeneca, UCB, Roche, Celgene, Sanofi and Horizon, but none of them relates to the content of this manuscript, D. Pisetsky: None declared, R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB and Wyeth, Consultant for: Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Celgene, Janssen (formerly Centocor), Galapagos, Glaxo-Smith-Kline, Novartis, Novo-Nordisk, Merck, Pfizer, Roche, Schering-Plough, TiGenix, UCB and Wyeth, Employee of: RL is director of Rheumatology Consultancy BV which is a registered company under Dutch law., Speakers bureau: Abbott/AbbVie, Amgen, Bristol Myers Squibb, Janssen (formerly Centocor), Merck, Pfizer, Roche, Schering-Plough, UCB and Wyeth, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boeringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB, Employee of: DH is director of Imaging Rheumatology bv., A. Sepriano: None declared, M. Aringer Grant/research support from: MA9s institution is clinical trial site for AbbVie, Astra Zeneca, Boehringer Ingelheim, Novartis, Pfizer and Roche., Consultant for: AbbVie, Astra Zeneca, BMS, Chugai, GSK, Hexal, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and UCB, Speakers bureau: AbbVie, Astra Zeneca, BMS, Chugai, GSK, Hexal, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and UCB, D. Boumpas: None declared, G. Burmester Grant/research support from: AbbVie, BMS, UCB and Roche, Speakers bureau: MSD, UCB and Roche, M. Cutolo Grant/research support from: BMS, Horizon, Actelion, Celgene and MSD, Speakers bureau: Biogen, Mundipharm, Pfizer and Menarini, W. Ebener Consultant for: Novartis and Abbvie, W. Graninger: None declared, T. Huizinga Consultant for: Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boeringher, Takeda, Epirus and Eli Lilly, G. Schett Speakers bureau: BMS, Celgene, Chugai, Lilly, Roche and UCB, H. Schulze-Koops Speakers bureau: AbbVie, Actelion, AstraZeneca, Biogen International, Boehringer Ingelheim, BMS, Celgene, Celltrion, Chugai, Cinfa Biotech, GSK, Hospira, Janssen-Cilag, Lilly, MSD, Medac, Merck, Mundipharma, Novartis, Pfizer, Hexal Sandoz, Roche and UCB, P. P. Tak Employee of: PPT has become an employee of GlaxoSmithKline. GSK has not been involved in this study., F. Breedveld: None declared, J. Smolen Grant/research support from: Abbvie, Lilly, MSD, Pfizer and Roche, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi and UCB
Purpose: Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described. Chondrocyte culture has been essential to understand cartilage degeneration, which is a hallmark of OA. We investigated the feasibility of human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints. Methods: Hyaline cartilage of the proximal interphalangeal (PIP) joint was obtained from 31 cadavers using two different protocols. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers and patients undergoing surgery for total knee replacement were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry. Results: Chondrocytes harvested up to 236 hours after death of the donors were viable. Compared to chondrocytes of the knee chondrocytes derived from PIP joints exhibited a specific gene expression pattern. Genes involved in developmental processes including the WNT pathway were differentially expressed. Real-time PCR and immunohistochemistry confirmed these results. Conclusions: These findings suggest that our knowledge on chondrocyte biology derived mainly from knee and hip joints may not apply to chondrocytes of the PIP joints and some of the distinctive features of HOA may be caused by the specific properties of PIP chondrocytes. Chondrocyte culture of PIP cartilage is a novel tool to study cartilage degeneration in HOA.
Background Patients with primary Sjögren Syndrome (PSS) are affected by glandular and extraglandular manifestations leading to physical and mental impairment. How these factors affect the health related quality of life (HRQL) of these patients is largely unexplored. Objectives This qualitative study was conducted to investigate patients9 perspectives and needs influencing HRQL in PSS. Methods We recruited 20 consecutive PSS patients fulfilling the American-European consensus classification criteria out of the PSS cohort of the Medical University Graz, Austria. A total of 6 focus group sessions were performed. A discussion guide with four open-ended questions was developed containing all elementary components of HRQL (physical, mental, social, daily life). All interviews were audio-recorded and transcribed verbatim. A modified meaning condensation procedure was used to analyse the data. Results All patients were female, the mean age was 61 (SD ±8) years and mean disease duration was 5 (±2) years. The focus group sessions took on average 58 ±13 minutes. The number of patients in each group ranged from three to four. The interview analysis resulted in 484 meaning units, 254 subconcepts and 87 concepts. The identified concepts were grouped into three dimensions: physical dimension, psychological & emotional challenges and social life & daily living. An inter-dependency of the three dimensions was identified. The concepts most commonly reported belonged to the physical dimension: pain, dryness and complaints related to these two symptoms. Patients frequently mentioned consequences of dryness including recurrent inflammation of eyes and ears, loss of sense of smell and taste, sleeping disturbances and the inability to eat and chew. In the dimension psychological & emotional challenges, the most frequently mentioned concepts were “being worried about the future”, “a long symptom to diagnosis lag” and “the feeling of being an encumbrance for their families”. Concepts like dependency on relatives in daily life, difficulties at work and financial burden were classified within the dimension of social life & daily living. Conclusions We found that three interrelated dimensions (physical dimension, psychological & emotional challenges and social life & daily living) best reflected patients9 experiences and feelings related to PSS. HRQL in PSS patients was influenced not only by dryness rather psychological and social burden clearly impacted the patients. Disclosure of Interest None declared
Background Psoriatic arthritis (PsA) belongs to the spondyloarthritides and disease activity can be evaluated by the Disease Activity Index for Psoriatic Arthritis (DAPSA) and the Composite Psoriatic Disease Activity Index (CPDAI) 1. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite disease activity score for ankylosing spondylitis covering peripheral involvement in both versions selected by ASAS international society (ASDASCRP and ASDASESR)2. Objectives To evaluate the possible importance of ASDASCRP and ASDASESR to assess disease activity in PsA. Methods In a cross-sectional study patients attending our outpatient clinic and fulfilling CASPAR criteria of PsA underwent a complete rheumatologic assessment to calculate the disease activity score CPDAI and DAPSA for PsA as well as the ASDASCRP and ASDASESR after informed consent was obtained. On the same day a rheumatologist unaware of the clinical status of the patients performed B-mode and power Doppler (PD) sonography of peripheral joints, of tendon sheets and entheses according to the MASEI, and of perisynovial tissue of finger joints. Results were graded semi-quantitatively and sum scores were calculated for PD signals and for pathological B-mode and PD findings together (GLUS, range 0–832). Descriptive statistics were used to summarise the data and correlations were analysed by the Spearman9s rank correlation test. Results 67 of 84 included patients (49 male, 18 female; mean age 51 (SD 12) years; median disease duration 7 years (IQR 4–18) could be evaluated. We found a strong correlation of the DAPSA and CPDAI score and a low but significant correlation of the GLUS and the PD sum score with the ASDASESR and ASDASCRP (table). We observed only a moderate association of the DAPSA with the GLUS (r=0.52, 95%CI 0.32–0.68) and the association of the CPDAI with the GLUS and the PD sum score (r=0.25, 95%CI 0.003–0.47 and r=0.19, 95%CI -0.06–0.42, respectively) was even lower than the correlation of the GLUS and the PD sum score with the ASDASESR and the ASDASCRP. In PsA-patients with clinically defined remission 25.0% of the patients fulfilled the CPDAI and 29.1% the DAPSA remission criteria. However, in patients with clinically defined remission 50.0% and 54.2% fulfilled the ASDASESR and ASDASCRP criteria for inactive disease. Conclusions This cross-sectional study shows that the ASDAS might also be a valuable tool to measure disease activity and to define clinical remission in PsA. References Helliwell PS. Assessment of disease activity in psoriatic arthritis. Clin Exp Rheumatol 2015;33:S44–7. Lukas C, Landewe R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:18–24. Disclosure of Interest None declared
ZUsAmmenfAssUng Abatacept stellt nach der verbreiteten Anwendung der Zytokinantagonisten ein zusätzliches Behandlungsprinzip der rheumatoiden Arthritis (RA) dar. Es handelt sich dabei um ein rekombinantes Fusionsprotein aus dem humanen CTLA4-Molekül und dem Fc-Rezeptorteil des Immunglobulins G1 (IgG1). Abatacept ist der erste Vertreter einer neuen Klasse von immunmodulatorischen Therapeutika, die sehr selektiv das zwischen den Oberflächenmolekülen CD80/CD86 und CD28 erfolgende, für die volle Aktivierung von T-Lymphozyten notwendige Signal beeinflussen.
Background Treatment decisions in Psoriatic Arthritis (PsA) depend upon the perception of disease activity by rheumatologists and patients. The factors explaining the variability of disease activity assessments, however, are elusive so far. Objectives The purpose of this study was the identification of clinical and/or ultrasound parameters explaining the discrepancy between patients' (PGA) and evaluator's global assessment (EGA) of disease activity in PsA. Methods We performed a prospective study on 83 consecutive PsA patients with study visits at baseline and after 6 months. All patients underwent the following clinical assessments: tender (TJ) and swollen joint (SJ) counts (68/66 joint count), PASI, dactylitis score and the Leeds Enthesitis Score. We also recorded the PGA, patients' pain assessment (pain VAS), the EGA (all measured on a 100mm VAS) as well as the Dermatology Life Quality Index (DLQI) and the HAQ. Ultrasound was performed by an independent investigator blinded to clinical results using an ESAOTE MyLab Twice ultrasound device (6–18 MHz and 4-13 MHz probes). Structural (erosions, osteophytes) and inflammatory changes [gray scale (GS) and Power Dopper (PD)] were investigated at 68 joints and 14 entheses. For statistical analysis, we used SPSS v22. Multivariate regression models were performed to identify the possible association between clinical or ultrasound parameters with EGA and PGA. Results Mean age of patients was 51.8 (±11.7) years, 26.2% were female, 43.4% were treated with methotrexate and 37.3% received anti-TNF agents. Disease activity was differently evaluated by patients and physicians in 65% of cases: in 53% (n=44) of patients, PGA scores were higher than EGA and vice versa, 12% (n=10) of cases had higher EGA scores. EGA and painVAS correlated strongly in patients with high PD scores (r=0.756 (p<0.001) in cases with a PD score >10) whereas a weak association was observed in patients with low levels of ultrasound inflammation, (r=0.376, p<0.05). Besides, a good correlation between EGA and painVAS (r=0.823, p<0.001) was found in patients with a high erosion score (>10) whereas in patients with low levels of structural damage, the correlation was weak (r=0.384, p<0.05). The association between PGA and EGA was not linked with the degree of ultrasound verified inflammation or damage. A multivariate regression model was conducted to identify clinical factors explaining the variability of PGA and EGA in PsA patients. Half of the variability of PGA results was explained by pain VAS (30.5%), swollen joints (15%) and tender joints (6.5%). Besides, pain VAS (B-coeff=0.534, P<0.001) and HAQ (B-coeff=6.266, P<0.05) were significant predictors of PGA. The variability of EGA results was mainly explained by the SJ count (48.5%), SJ also predicted EGA levels (B-coeff=3.098, P<0.001). In the ultrasound model half of the variability of PGA was explained by pain VAS (42.9%) and GSS-joints (4.7%) while the EGA results were clarified by GSS-joints (12.9%), HAQ-score (9.8%), pain VAS (9.1%) and PD-joints (6.6%). Conclusions EGA and painVAS better correlate in PsA patients with high compared to low levels of ultrasound verified inflammation or damage. PainVAS and SJ are the most important clinical determinants of PGA and EGA, respectively whereas the most relevant ultrasound parameters were the GSS-joints and PD-joints score. Disclosure of Interest None declared
Hintergrund: Regulatorische T Zellen (Tregs) haben eine wichtige Rolle in der Regulation von Immuntoleranz und Störungen der Funktion von Tregs sind in der Pathogenese des Diabetes Typ 1 (T1D) involviert. In dieser Studie war das Ziel die Anzahl, Suppressionsfunktion und Apoptoseneigung von Tregs in Kindern und Erwachsenen mit T1D und kurzer Diabeteslaufdauer sowie Verwanden 1. Grades (FDR) und gesunden Kontrollen zu vergleichen.