Rheumatoid Arthritis: Steinfeld SD

Steinfeld SD, Youinou P. · Erasme University Hospital, Department of Rheumatology, Route de Lennik 808, Brussels 1070, Belgium. · Expert Opin Biol Ther. · Pubmed #16918261 No free full text.

Abstract: B cells play an important role in the pathogenesis of many autoimmune diseases. Different approaches targeting the B cell compartment are under investigation. Selective modulation of B cells has been recently achieved using a humanised monoclonal antibody against the B cell surface marker CD22. This antibody (epratuzumab) was originally developed for the treatment of non-Hodgkin's lymphoma and was found to be effective, with a very good safety profile. Recent studies have demonstrated the efficacy and safety of epratuzumab in several autoimmune diseases, including systemic lupus erythematosus and primary Sjögren's syndrome.

Steinfeld SD, Tant L, Burmester GR, Teoh NK, Wegener WA, Goldenberg DM, Pradier O. · Department of Rheumatology, Erasme University Hospital, 808 Route de Lennik, Brussels 1070, Belgium. · Arthritis Res Ther. · Pubmed #16859536 links to  free full text

Abstract: This open-label, phase I/II study investigated the safety and efficacy of epratuzumab, a humanised anti-CD22 monoclonal antibody, in the treatment of patients with active primary Sjögren's syndrome (pSS). Sixteen Caucasian patients (14 females/2 males, 33-72 years) were to receive 4 infusions of 360 mg/m2 epratuzumab once every 2 weeks, with 6 months of follow-up. A composite endpoint involving the Schirmer-I test, unstimulated whole salivary flow, fatigue, erythrocyte sedimentation rate (ESR), and immunoglobulin G (IgG) was devised to provide a clinically meaningful assessment of response, defined as a > or = 20% improvement in at least two of the aforementioned parameters, with > or = 20% reduction in ESR and/or IgG considered as a single combined criterion. Fourteen patients received all infusions without significant reactions, 1 patient received 3, and another was discontinued due to a mild acute reaction after receiving a partial infusion. Three patients showed moderately elevated levels of Human anti-human (epratuzumab) antibody not associated with clinical manifestations. B-cell levels had mean reductions of 54% and 39% at 6 and 18 weeks, respectively, but T-cell levels, immunoglobulins, and routine safety laboratory tests did not change significantly. Fifty-three percent achieved a clinical response (at > or = 20% improvement level) at 6 weeks, with 53%, 47%, and 67% responding at 10, 18, and 32 weeks, respectively. Approximately 40%-50% responded at the > or = 30% level, while 10%-45% responded at the > or = 50% level for 10-32 weeks. Additionally, statistically significant improvements were observed in fatigue, and patient and physician global assessments. Further, we determined that pSS patients have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy. Thus, epratuzumab appears to be a promising therapy in active pSS, suggesting that further studies be conducted.

Steinfeld SD, Demols P, Salmon I, Kiss R, Appelboom T. · Department of Rheumatology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Arthritis Rheum. · Pubmed #11665979 No free full text.

Abstract: OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine involved in the pathogenesis of Sjögren's syndrome (SS), and blockade of TNFalpha may reduce the activity of the disease. The purpose of this study was to evaluate the safety and potential efficacy of infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody, in patients with active primary SS. METHODS: This was a single-center, open-label pilot study. Sixteen patients with active primary SS received 3 infusions of infliximab (3 mg/kg) at 0, 2, and 6 weeks. Standard clinical assessment, complete ophthalmologic testing, and functional evaluation of salivary flow were performed at baseline and at weeks 2, 6, 10, and 14. RESULTS: All patients completed the study. There was statistically significant improvement in all clinical and functional parameters, including global assessments (patient's global assessment, patient's assessment of pain and fatigue, physician's global assessment), erythrocyte sedimentation rate, salivary flow rate, the Schirmer I test, tender joint count, fatigue score, and dry eyes and dry mouth. This clinical benefit was observed at week 2 and was maintained throughout the study and the 2-month followup period. The treatment was well tolerated in all patients, and no significant adverse events were seen. No lupus-like syndrome was observed, and no anti-double-stranded DNA antibodies were observed that were attributable to infliximab therapy. CONCLUSION: In patients with active primary SS, a loading-dose regimen of 3 infusions of infliximab provided a fast and significant clinical benefit without major adverse reactions. It was possible to maintain statistically significant improvement for up to 8 weeks after the third infusion.

Steinfeld SD, Demols P, Van Vooren JP, Cogan E, Appelboom T. · Division of Rheumatology, Erasmus Academic Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Rheumatology (Oxford). · Pubmed #10515640 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy of the administration of zidovudine (AZT), an antiretroviral drug, in patients with primary Sjögren's syndrome (SS). METHODS: Seven female patients (age 57 +/- 8.6 yr) with primary SS were enrolled in an open, uncontrolled trial of AZT (250 mg b.i.d.) for the treatment of primary SS. The efficacy variables were oral and ocular dryness symptoms, fatigue, tender points, physician's and patient's global assessments (GA), ocular function tests (fluorescein tear break-up time, Schirmer's test, Rose Bengal staining) and laboratory parameters [erythrocyte sedimentation rate (ESR), serum IgG, IgA and IgM]. RESULTS: A significant improvement was observed in all subjective manifestations, as well as the objective parameters of ocular dryness. The treatment was well tolerated, except for mild and transitory gastrointestinal disturbances in 6/7 patients. Laboratory parameters did not change significantly. The clinical benefit persisted in 5/7 patients 1 month after the end of therapy. CONCLUSION: AZT seems to be effective and well tolerated in patients with primary SS.

Soyfoo MS, De Vriese C, Debaix H, Martin-Martinez MD, Mathieu C, Devuyst O, Steinfeld SD, Delporte C. · Laboratory of Biochemistry, Université Libre de Bruxelles, Route de Lennik 808, B-1070 Brussels, Belgium. · Arthritis Rheum. · Pubmed #17665453 links to  free full text

Abstract: OBJECTIVE: To investigate the expression and localization of aquaporin 5 (AQP5) in salivary glands and salivary gland function in the NOD mouse. METHODS: All experiments were performed using NOD and BALB/c mice (ages 8 weeks and 24 weeks). Real-time reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical analysis were used to study the expression and distribution of AQP5 in salivary glands. In addition, salivary gland function was determined. RESULTS: Compared with the levels in BALB/c mice, relative AQP5 messenger RNA levels were not significantly modified in the parotid glands from NOD mice of both ages but were significantly increased in the submandibular glands from NOD mice of both ages. Western blot analyses of both salivary gland membranes revealed that the level of AQP5 protein was increased in 24-week-old NOD mice. Important inflammatory infiltrates were observed in the submandibular glands, but not in the parotid glands, from 24-week-old NOD mice. The 8-week-old and 24-week-old BALB/c mice and the 8-week-old NOD mice showed AQP5 primarily at the apical membrane of the salivary gland acinus. In contrast, in acini from the submandibular glands (but not the parotid glands) from 24-week-old NOD mice, AQP5 staining was reduced at the apical membrane but was increased at the basal membrane. A moderately statistically significant decrease in pilocarpine-stimulated salivary flow was observed in 24-week-old NOD mice compared with that in age-matched BALB/c mice. CONCLUSION: Submandibular glands from 24-week-old NOD mice displayed inflammatory infiltrates, increased AQP5 protein expression, and impaired AQP5 distribution. However, the moderately statistically significant decrease in the salivary flow rate in these mice did not match the extent of AQP5 misdistribution.

Steinfeld SD, Demols P, Appelboom T. · Department of Rheumatology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Arthritis Rheum. · Pubmed #12483735 links to  free full text

Abstract: OBJECTIVE: To evaluate the safety and efficacy of a maintenance regimen of infliximab in patients with active primary Sjögren's syndrome (SS) over a 1-year period. METHODS: This followup study included 10 of the 16 patients with primary SS who participated in a pilot study. Patients who continued to have symptoms received additional infusions of infliximab for 1 year. RESULTS: All patients completed the 1-year followup for evaluation of efficacy. After 1 year, a statistically significant decrease in global and local disease manifestations was observed in all 10 patients. Treatment was generally well tolerated, with the main side effect being a mild, self-limited infusion reaction. CONCLUSION: Sustained improvement of active primary SS may be possible with infliximab treatment.

Caroyer JM, Manto MU, Steinfeld SD. · Department of Neurology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Neurology. · Pubmed #12370480 No free full text.

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Steinfeld SD, Appelboom T, Delporte C. · Erasme University Hospital Christine Delporte, Brussels, Belgium. · Arthritis Rheum. · Pubmed #12209534 links to  free full text

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Steinfeld SD, Delporte C. · No affiliation provided · Lancet. · Pubmed #12049892 No free full text.

This publication has no abstract.