Rheumatoid Arthritis: Dass S

Dass S, Vital EM, Emery P. · Academic Unit of Musculoskeletal Disease, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK. · Expert Opin Pharmacother. · Pubmed #17150009 No free full text.

Abstract: Significant numbers of patients with rheumatoid arthritis (RA) suffer from disease that is refractory to both conventional therapy and newer biological agents such as TNF-alpha inhibitors. These patients may respond insufficiently, lose an effective response, develop toxicity or carry contraindications to such agents. Rituximab, a chimeric monoclonal antibody against CD20 that effectively depletes B cells in peripheral blood, has been licensed for the treatment of certain haematological malignancies for almost 10 years. B cells are now known to have multiple key roles in the pathogenesis of RA. Data is now available that indicates efficacy and safety of B-cell depletion with rituximab in the treatment of RA in a variety of patient groups. The clinical outcomes from these studies, together with its safety profile, have led to rituximab being licensed for the treatment of patients with RA who have failed to obtain benefit from anti-TNF-alpha agents.

Dass S, Rawstron AC, Vital EM, Henshaw K, McGonagle D, Emery P. · University of Leeds, and Leeds Teaching Hospitals National Health Service Trust, Leeds, UK. · Arthritis Rheum. · Pubmed #18821683 No free full text.

Abstract: OBJECTIVE: In rheumatoid arthritis (RA), B cell depletion occurs in all patients treated with rituximab, but the clinical responses to rituximab are variable. A highly sensitive assay was used to test the hypothesis that B cell depletion is variable, and that incomplete depletion leads to a poorer outcome. METHODS: Sixty patients with active RA unresponsive to anti-tumor necrosis factor agents received two 1-gram infusions of rituximab. B cell numbers were measured by highly sensitive flow cytometry before and after each infusion and at 3-month intervals thereafter. A reduction in B cell levels below 0.0001x10(9)/liter was defined as complete depletion (compared with 0.05x10(9)/liter by conventional cytometry). Clinical responses were measured using the European League Against Rheumatism (EULAR) criteria. RESULTS: At 6 months, 92% of patients had a moderate-to-good clinical response according to the EULAR criteria. B cells were detected in 63% of patients after the first infusion of rituximab (median level 0.0009x10(9)/liter [range<0.0001-0.0015x10(9)/liter), and these patients had poorer clinical outcomes than patients with complete depletion. At 9 months, 82% of patients with complete depletion had a moderate-to- good EULAR response, compared with 43% of those with partial depletion (P=0.01). At 12 months, 59% of complete responders had a moderate-to-good EULAR response, compared with 21% of those with partial depletion (P=0.01). Patients in whom B cells were depleted only after the second infusion did no better than those in whom depletion was never complete and had poorer clinical outcomes than those in whom depletion was initially complete. CONCLUSION: This study is the first to show, using a highly sensitive analysis, that rituximab therapy is associated with variable diminution in B cell numbers. A lack of complete depletion of B cells after 1 infusion was associated with a poorer outcome.

Dass S, Bowman SJ, Vital EM, Ikeda K, Pease CT, Hamburger J, Richards A, Rauz S, Emery P. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · Ann Rheum Dis. · Pubmed #18276741 No free full text.

Abstract: OBJECTIVE: Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. METHODS: A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. RESULTS: There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. CONCLUSIONS: This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

Freeston JE, Conaghan PG, Dass S, Vital E, Hensor EM, Stewart SP, Emery P. · Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK. · Ann Rheum Dis. · Pubmed #17666445 No free full text.

Abstract: BACKGROUND: Long-standing rheumatoid arthritis produces unique challenges when assessing damage due to joint deformity. The use of extremity magnetic resonance imaging (eMRI) offers the possibility of improved disease assessment because of greater patient tolerability. OBJECTIVES: The aim of this cross-sectional study was to compare the identification of wrist erosions in a severe rheumatoid arthritis cohort by eMRI with a restricted field of view (eMRI-RV) to radiography and high field MRI, using the latter as the reference. METHODS: Fifteen patients (87% female, median age 56 years) with active rheumatoid arthritis (median DAS28 7.01 and disease duration 11 years) on leflunomide were enrolled. Radiography of hands, eMRI-RV (0.2 T MagneVu MV 1000) and high field MRI of unilateral wrist joints were performed. RESULTS: Of 86 comparable wrist joint areas, high field MRI identified 70 erosions, eMRI-RV 32 and radiography 4. With high field MRI considered the reference, the sensitivity, specificity and accuracy of eMRI-RV for erosions were 46%, 94% and 55%, and the corresponding values for x ray were 6%, 100% and 23%, respectively. CONCLUSIONS: In severely damaged rheumatoid arthritis joints, sensitivity of erosion detection was markedly higher for eMRI-RV than radiography, using high field MRI as the reference. eMRI-RV was, however, less sensitive than high field MRI.

Dass S, Vital EM, Emery P. · Academic Unit of Musculoskeletal Disease, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds, UK. · Arthritis Rheum. · Pubmed #17665440 links to  free full text

Abstract: The B cell-depleting monoclonal antibody rituximab is a novel therapy for the rheumatic diseases, with an increasing body of evidence regarding its safety and efficacy in an expanding range of indications. However, there is uncertainty over its potential use in, and impact on, autoantibody-negative diseases. We describe 3 patients, with no known risk factor for psoriasis, who developed psoriasis (and 1 who also developed features of psoriatic arthritis) after receiving rituximab for a variety of indications, namely, seropositive and seronegative rheumatoid arthritis and systemic lupus erythematosus. In all cases, the underlying disease responded well to rituximab. The interpretation of this possible side effect of rituximab remains unclear, but a B cell-depleted environment may induce abnormal T cell responses, possibly provoked either by subclinical infection or by the removal of mechanisms whereby B cells regulate T cells. These cases suggest that the pathogenesis of psoriasis may not require normal numbers of B cells and that proposed treatment of psoriasis and psoriatic arthritis with rituximab may result in unpredictable responses.

Vital EM, Dass S, Buch MH, Rawstron AC, Ponchel F, McGonagle D, Emery P. · No affiliation provided · Arthritis Rheum. · Pubmed #19479853 No free full text.

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