Disease Remission In Rheumatoid Arthritis Research Articles

The prevalence and types of discordance between physician perception and objective data from standardized measures of rheumatoid arthritis disease activity in real-world clinical practice in the US

BackgroundHeterogeneity in assessments of rheumatoid arthritis (RA) disease remission, based on physician judgment and patient self-reports versus standardized measures, have previously been reported. This study explored the prevalence and types of discordance between physician perception versus objective data of RA disease activity in real-world clinical practice in the US.MethodsData were from the Adelphi RA Disease Specific Programme (DSP; January to March 2014), a cross-sectional survey of US rheumatologists and their patients. RA remission based on physician judgment versus Disease Activity Score in 28 joints (3)-erythrocyte sedimentation rate (DAS28(3)-ESR) and Clinical Disease Activity Index (CDAI) scores were compared using descriptive analyses; patient and physician factors associated with discordance were identified using bivariate and multivariate analyses.ResultsOf 101 rheumatologists participating (completing patient-record forms for 843 patients), 56.4% based assessment of remission on clinical judgment alone. Of 531 patients eligible for the discordance analysis, 49.7% were in remission based on rheumatologists’ evaluation, and 30.7% were eligible based on DAS28(3)-ESR. Compared with DAS28(3)-ESR criteria, 25.8% of patients’ disease remission was negatively discordant (overestimated remission) based on clinical perception. These patients were mostly administered biologic disease-modifying antirheumatic drugs and were without a treat-to-target strategy followed by their rheumatologist (P < 0.05). These patients were also more likely to have experienced a higher level of pain as well as increased joint inflammation and damage (e.g. destruction of cartilage, thinning of bone, and/or synovium inflammation) compared with concordant patients (P < 0.005). Conversely, 6.8% of rheumatologists were positively discordant (under estimated remission) versus the DAS28(3)-ESR. Sensitivity analysis indicated different levels of discordance using CDAI, with 35.6% negative discordance and 1.3% positive discordance of rheumatologist-assessed disease remission compared with objective data.ConclusionThere is discordance between RA remission as assessed by rheumatologist perception versus standardized measures among those in the US DSP sample. Our study identified the factors associated with the discordance which may inform strategies to enhance assessments of RA disease remission.

Enhanced interferon gamma response contributes to disease remission in Rheumatoid Arthritis.

Abstract Rheumatoid arthritis (RA) is an autoimmune disease with debilitating bilateral inflammation in multiple joints. Although newer biologics are very effective in managing RA, critical gaps in immunopathogenic mechanism remain. We recently showed that increased expression of the interferon gamma (IFN-γ) receptor in PBMC associated with RA and increased radiographic severity. We hypothesized that enhanced IFN-γ signaling in specific subpopulations of mononuclear cells from patients with RA contributes to disease severity. To test this, we collected PBMC from healthy controls (HC) and RA patients in remission, low disease and moderate disease severity as per American College Criteria. As an autoimmune disease control, we compared PBMC from treatment naïve multiple sclerosis (MS) patients. We quantitated classical (JAK/STAT) and non-classical (ERK/MTOR) IFN-γ induced signaling in subpopulations of T and B cells within PBMC using phospho-flow cytometry. For analysis we utilized t-SNE and SPADE data visualization and clustering tools to interrogate changes in activation and marker expression within and between T and B cell populations. We observed IFN-γ-induced activation of STAT1 in CD4+ naïve and central memory T-cells from was greatest in RA patients in remission and lowest in individuals with moderate disease. IFN-γ induced activation of STAT1 in all CD8+ T-cell sub-populations of RA were similar to that from HC. Furthermore, the activation of STAT1 in all CD4+ T-cell sub-populations in PBMC from MS patients very generally greater than from RA patients and HC. From our results we infer that that while expression of IFNGR correlates with disease in RA, gain in response to IFN-γ is indicative of treatment response and RA remission.

Impaired CD27+IgD+ B Cells With Altered Gene Signature in Rheumatoid Arthritis.

Natural antibodies, particularly natural IgM, are proved to play indispensable roles in the immune defenses against common infections. More recently, the protective roles of these natural IgM were also recognized in autoimmune diseases. They are mainly produced by B-1 and innate-like B cells (ILBs). Human CD19+CD27+IgD+ B cells, also termed as un-switched memory B cells, were proposed to be a kind of ILBs. However, functional features and characteristics of these cells in rheumatoid arthritis (RA) remained poorly understood. In this study, we found that human CD27+IgD+ B cells could produce natural antibody-like IgM. Under RA circumstance, the frequencies of these cells were significantly decreased. Moreover, the IgM-producing capacities of these cells were also dampened. Interestingly, the BCR repertoire of these cells was altered in RA, demonstrating decreased diversity with preferential usage alteration from VH3-23D to VH1-8. Single cell sequencing further revealed the proinflammatory biased features of these cells in RA. These CD27+IgD+ B cells were negatively correlated with RA patient disease activities and clinical manifestations. After effective therapy with disease remission in RA, these cells could be recovered. Taken together, these results have revealed that CD27+IgD+ B cells were impaired in RA with dysfunctional features, which might contribute to the disease perpetuation.

Impairment of Granzyme B-Producing Regulatory B Cells Correlates with Exacerbated Rheumatoid Arthritis

Hyperactivated B cells have been demonstrated the contribution to the development of rheumatoid arthritis (RA). While the recognition of the negative regulatory function of B cells further promoted our understanding of their pathogenic role in RA. Recently, a new population of granzyme B (GrB)-producing B cells was identified, which was proved to be involved in cancer and infectious diseases. However, their characteristics and roles in RA remain to be elucidated. In the present study, we aim to further characterize whether B cells could produce GrB and reveal their potential role in the pathogenesis of RA. Here, we further demonstrated peripheral blood B cells from healthy individuals could produce and secrete GrB, which could be enhanced by IL-21 and/or anti-B-cell receptor stimulation. These cells could negatively regulate Th1 and Th17 cells partly via downregulating TCR zeta chain and inducing T cell apoptosis, which might be termed as GrB-producing regulatory B cells (Bregs). These GrB-producing Bregs were significantly decreased under RA circumstance concomitant of lower levels of IL-21 receptor, with impaired regulatory functions on Th1 and Th17 cells. Moreover, the frequencies of these cells were negatively correlated with RA patient disease activity and clinical features. After effective therapy with disease remission in RA, these GrB-producing Bregs could be recovered. Therefore, our data revealed that B cells could produce GrB with immunosuppressive functions, and the impairment of this Breg subset was correlated with RA pathogenesis.

Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane Systematic Review and network meta-analysis (NMA).

Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane Systematic Review and network meta-analysis (NMA).

THU0094 Direct comparison of four biological agents in bio-naïve rheumatoid arthritis patients

BackgroundThe treatment of rheumatoid arthritis (RA) has changed significantly, and biological agents now occupy an extremely prominent position in treatment strategies. The 2010 EULAR recommendations list TNF inhibitors as the...

SAT0035 Variability in the Classification of Remission among Disease Activity Indices and Their Correlation: An Analysis From a Prospective, Observational Registry

BackgroundIn recent years, disease remission in rheumatoid arthritis (RA) has been assessed using various disease activity indices such as the DAS28, SDAI, CDAI, ACR/EULAR-recommended Boolean definition and the Patient Activity...

Interleukin‐6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: The role of acute‐phase reactants

To determine the effects of tocilizumab on rheumatoid arthritis (RA) disease activity and remission assessment, using measures that do or do not comprise acute-phase reactants. Simplified Disease Activity Index (SDAI) scores, Clinical Disease Activity Index (CDAI) scores, and the Disease Activity Score in 28 joints (DAS28) were calculated using data from tocilizumab trials in patients with RA in whom disease had remained active despite treatment with disease-modifying antirheumatic drugs. The CDAI does not contain an acute-phase reactant component. Disease activity states, including remission, were defined using established cut points; for the DAS28, an alternative cut point of <2.4 was also used. Changes in the DAS28, the SDAI score, and the CDAI score among patients receiving tocilizumab were significantly higher than those among patients receiving placebo, and the magnitude of these changes was similar for the SDAI and the CDAI. Among patients who achieved 50% improvement in disease activity according to the American College of Rheumatology criteria, only ∼20% required a reduction in acute-phase reactant values in order to fulfill the criteria. However, DAS28 remission rates were higher (even when using the lower cut point) than the SDAI and CDAI remission rates. Only a minority of tocilizumab-treated patients with DAS28 remission also had disease remission according to the SDAI (26%) or CDAI (∼21%). With infliximab treatment, SDAI and CDAI remission rates were of the same magnitude as those observed with tocilizumab treatment, and DAS28 remission rates were lower. Tocilizumab-treated patients with DAS28 remission but without CDAI remission had significantly higher swollen joint counts but lower erythrocyte sedimentation rates (ESRs) compared with patients with SDAI or CDAI remission. Disease activity in RA is reduced by tocilizumab treatment, irrespective of the type of composite measure used to evaluate disease activity. Remission rates were much higher using the DAS28 compared with the SDAI and CDAI, due to the high weight of the ESR in the DAS28 and the effect of tocilizumab on the ESR. Using the stringent SDAI and CDAI criteria, however, remission rates in patients treated with tocilizumab were in the same range as those seen in patients treated with tumor necrosis factor inhibitors.

Improved glycaemic control with disease remission in rheumatoid arthritis and hypoglycaemic effect of sulphasalazine

Improved glycaemic control with disease remission in rheumatoid arthritis and hypoglycaemic effect of sulphasalazine

Therapeutic monoclonal antibodies.

Monoclonal antibodies have been used extensively over the last few years in clinical trials of rheumatoid arthritis (RA). Not only are they potential therapeutic agents, but they are also useful probes into the immunopathogenesis of RA. Anti-tumour necrosis factor alpha (TNF alpha) monoclonal antibodies have been shown to be clinically efficacious. Although they produced rapid disease amelioration, the duration of clinical improvement was limited to 4-6 weeks. Re-treatments were again effective but long-term studies are required to assess their therapeutic role in RA. So far, the therapeutic effects of lymphocyte-depleting antibodies have been disappointing. From the data, it is clear that synovial lymphocytes are more difficult to eliminate than peripheral blood lymphocytes and it is likely that in order to delete all synovial lymphocytes, high doses of depleting antibodies will be required which could lead to severe immunosuppression. Hence, lymphocyte depletion may not be a feasible therapeutic strategy. However, there are a number of clinical trials currently underway attempting to inhibit CD4 lymphocyte function by non-depleting antibodies. In animal models of RA, such antibodies have been shown to induce long-term disease remission. Another possibility is to combine several monoclonal antibodies in order to induce disease remission in RA. This strategy has been used in murine collagen-induced arthritis in which a combination of anti-CD4 and anti-TNF alpha monoclonal antibodies was shown to be synergistic.