This study of ANCA-associated vasculitis compared a single course of rituximab with conventional immunosuppression with cyclophosphamide followed by azathioprine and showed similar results for the ...primary outcome of complete remission by 6 months, maintained through 18 months.
Granulomatosis with polyangiitis (previously termed Wegener's granulomatosis) and microscopic polyangiitis are called antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides because they are frequently accompanied by autoantibodies against proteinase 3 or myeloperoxidase.
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For nearly four decades, cyclophosphamide and glucocorticoids have been the standard therapy for the induction of remission. However, the primary results of the Rituximab in ANCA-Associated Vasculitis (RAVE) trial
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and results from a European trial
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showed that rituximab was as effective as cyclophosphamide for the induction of remission in patients with severe disease. Moreover, the rituximab-based regimen was superior in patients who had relapsing disease at 6 months.
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Rituximab has . . .
To evaluate whether the classification of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) according to ANCA type (anti-proteinase 3 (PR3) or anti-myeloperoxidase ...(MPO) antibodies) predicts treatment response.
Treatment responses were assessed among patients enrolled in the Rituximab in ANCA-associated Vasculitis trial according to both AAV diagnosis (granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA)) and ANCA type (PR3-AAV/MPO-AAV). Complete remission (CR) was defined as disease activity score of 0 and successful completion of the prednisone taper.
PR3-AAV patients treated with rituximab (RTX) achieved CR at 6 months more frequently than did those randomised to cyclophosphamide (CYC)/azathioprine (AZA) (65% vs 48%; p=0.04). The OR for CR at 6 months among PR3-AAV patients treated with RTX as opposed to CYC/AZA was 2.11 (95% CI 1.04 to 4.30) in analyses adjusted for age, sex and new-onset versus relapsing disease at baseline. PR3-AAV patients with relapsing disease achieved CR more often following RTX treatment at 6 months (OR 3.57; 95% CI 1.43 to 8.93), 12 months (OR 4.32; 95% CI 1.53 to 12.15) and 18 months (OR 3.06; 95% CI 1.05 to 8.97). No association between treatment and CR was observed in the MPO-AAV patient subset or in groups divided according to AAV diagnosis.
Patients with PR3-AAV respond better to RTX than to CYC/AZA. An ANCA type-based classification may guide immunosuppression in AAV.
NCT00104299; post-results.
This multicenter, randomized, double-blind, double-dummy, noninferiority trial compared rituximab with cyclophosphamide for remission induction in ANCA−associated vasculitis. Rituximab therapy was ...not inferior to daily cyclophosphamide treatment for remission induction in severe ANCA-associated vasculitis and may be superior in relapsing disease.
Rituximab therapy was not inferior to daily cyclophosphamide treatment for remission induction in severe ANCA-associated vasculitis and may be superior in relapsing disease.
Wegener's granulomatosis and microscopic polyangiitis are classified as antineutrophil cytoplasmic antibody (ANCA)−associated vasculitides because most patients with generalized disease have antibodies against proteinase 3 or myeloperoxidase.
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The ANCA-associated vasculitides affect small-to-medium-size blood vessels, with a predilection for the respiratory tract and kidneys.
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–
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Cyclophosphamide and glucocorticoids have been the standard therapy for remission induction for nearly four decades.
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This regimen transformed the usual treatment outcome of severe ANCA-associated vasculitis from death to a strong likelihood of disease control and temporary remission.
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However, not all patients have a remission with this combination of drugs, and those . . .
Scleroderma is a life-threatening autoimmune disease in need of more effective treatment. A randomized trial of myeloablative therapy followed by autologous CD34+ hematopoietic stem-cell ...transplantation showed outcomes that were superior to those with monthly cyclophosphamide.
Regulatory B cells control inflammation and autoimmunity in mice, including the recently identified IL-10–competent B10 cell subset that represents 1% to 3% of spleen B cells. In this study, a ...comparable IL-10–competent B10 cell subset was characterized in human blood. B10 cells were functionally identified by their ability to express cytoplasmic IL-10 after 5 hours of ex vivo stimulation, whereas progenitor B10 (B10pro) cells required 48 hours of in vitro stimulation before they acquired the ability to express IL-10. B10 and B10pro cells represented 0.6% and approximately 5% of blood B cells, respectively. Ex vivo B10 and B10pro cells were predominantly found within the CD24hiCD27+ B-cell subpopulation that was able to negatively regulate monocyte cytokine production through IL-10–dependent pathways during in vitro functional assays. Blood B10 cells were present in 91 patients with rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, autoimmune vesiculobullous skin disease, or multiple sclerosis, and were expanded in some cases as occurs in mice with autoimmune disease. Mean B10 + B10pro-cell frequencies were also significantly higher in patients with autoimmune disease compared with healthy controls. The characterization of human B10 cells will facilitate their identification and the study of their regulatory activities during human disease.
Objective
To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
Methods
We developed clinically relevant population, intervention, comparator, and outcomes (PICO) ...questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
The guideline addresses treatment with disease‐modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high‐risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).
Conclusion
This clinical practice guideline is intended to serve as a tool to support clinician and patient decision‐making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision‐making process based on patients’ values, goals, preferences, and comorbidities.
Objective
To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA).
Methods
We conducted systematic reviews to synthesize the evidence for the benefits and ...harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences.
Results
The guideline covers the use of traditional disease‐modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat‐to‐target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional.
Conclusion
This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision‐making process taking into account patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
Objectives. Identifying patients with RA at high risk of rapid radiographic progression (RRP) is critical for making appropriate treatment decisions. We developed an exploratory prediction model for ...the risk of RRP using an RA study population undergoing either conservative or aggressive disease management. Methods. Using data from the active-controlled study of patients receiving infliximab for the treatment of rheumatoid arthritis of early onset (ASPIRE) early RA study, RRP was defined as a threshold change in modified Sharp/van der Heijde score (SHS) of ⩾5 U/year. Spearman's rank analysis was used to identify baseline risk factors for RRP. Logistic regression was used to calculate the probability of RRP in 1 year. The results were combined into a matrix model that consisted of risk factors and initiated treatment arranged in increasing risk of RRP. Data from the anti-TNF trial in rheumatoid arthritis with concomitant therapy (ATTRACT) established RA study were applied to the model to test its generalizability in another population. Results. The 28 swollen joint count, RF, CRP and ESR are included as trichotomous variables and initiated treatment (monotherapy or combination therapy) as a dichotomous variable. Two models, one incorporating all risk factors except CRP and another incorporating all risk factors except ESR, were developed to adjust for collinearity. These models identify subpopulations of RA patients at higher predicted risk for RRP. Conclusions. These preliminary matrix models predict the risk of RRP using initiated treatment and easily accessible clinical and laboratory variables. Further testing in other populations and with other therapies is needed to obtain a definitive risk model that will guide rheumatologists in making treatment decisions for individual RA patients.
Recent advances have led to the development of mAbs that effectively deplete B cells in human beings and target pathways essential for B-cell development. B cell–directed therapies represent ...promising treatments for autoimmune disorders, although many questions remain about their optimal use in the clinic. Autoantibody depletion correlates with the clinical effectiveness of these drugs in some diseases but not all. This finding implies that self-reactive B cells are playing important pathogenic roles in autoimmune disorders beyond the production of autoantibodies. Clinical studies of B cell–directed therapies are beginning to illuminate the effects of B-cell modulation on immune function using a variety of mechanistic approaches, including delineation of B-cell subsets by flow cytometry, measurement of serum autoantibodies and cytokines, and tests of immunocompetence. Recent clinical studies have been performed in patients with rheumatoid arthritis and SLE suggesting the depletion of memory cells accounts at least in part for the clinical efficacy of rituximab therapy, but these findings, although provocative, require further investigation in larger cohorts. Memory B cells are not the only targets of depleting antibodies; therefore, other B-cell populations of therapeutic relevance may be modulated by these interventions. Moreover, pathologic B-cell responses may be favorably influenced by other targeted approaches such as those using anti–B-cell activating factor belonging to the TNF family (BAFF) or anti-CD22 antibodies.
Objective
To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
Methods
We developed clinically relevant population, intervention, comparator, and outcomes (PICO) ...questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
The guideline addresses treatment with disease‐modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high‐risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).
Conclusion
This clinical practice guideline is intended to serve as a tool to support clinician and patient decision‐making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision‐making process based on patients’ values, goals, preferences, and comorbidities.
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