Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren's syndrome: an open-label phase I/II study

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/m(2 )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 ≥20% improvement in at least two of the aforementioned parameters, with ≥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 ≥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 ≥30% level, while 10%–45% responded at the ≥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

Contribution à la physiopathologie du syndrome de Sjögren: implications de la prolactine et de l'aquaporine-5

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Les anticorps anti-peptides cycliques citrullinés (anti-CCP): Intérêt diagnostique et pronostique dans la polyarthrite rhumatoïde

Rheumatoid arthritis is an auto-immune disorder which diagnosis is based on clinical, radiological and biological criteria. Disease progression is characterized by appearance of bone erosions and progressive articular deformations which attenuate functional mobility. Only rheumatoid factor is actually considered as biological factor among recognized diagnostical criteria despite its weak sensibility and specificity rates. Anti-cyclic citrullinated peptides antibodies are directed toward citrullinated isoforms of some filaggrin's epitopes. Their sensitivity and specificity reach respectively 80 and 99%. Their presence is correlated to disease activity and to bone erosions development. They allow early identification and treatment of rheumatoid arthritis affected patients which is actually considered as a priority.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Epratuzumab (humanised anti-CD22 antibody) in autoimmune diseases

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. © 2006 Informa UK Ltd.SCOPUS: re.jinfo:eu-repo/semantics/publishe

New approaches to the treatment of Sjögren's syndrome: Soon beyond symptomatic relief?

Sjögren's syndrome (SS) is a common autoimmune disease characterized by destruction and dysfunction of the salivary and lachrymal glands. Systemic manifestations occur in almost one third of patients with SS. Treatment of SS has been long considered as disappointing, being mainly restricted to local management with artificial tears and oral lubricants or to the use of immunosuppression-based therapies for systemic disease. Better knowledge of the pathogenesis of SS, including the role of retroviruses and cytokines and the discovery of aquaporins, provides new perspectives for the local and systemic management of this disease. Our goal is to focus on these recent therapeutic progresses. Copyright © 2003 S. Karger AG, Basel.SCOPUS: ed.jinfo:eu-repo/semantics/publishe

Results from a patient survey to assess gastrointestinal burden of non-steroidal anti-inflammatory drug therapy contrasted with a review of data from EVA to determine satisfaction with rofecoxib

Non-steroidal anti-inflammatory drugs (NSAIDs) have frequently been linked with unpleasant gastrointestinal (GI) side-effects such as dyspepsia and ulcers. The present study investigated the burden of NSAID therapy from a patient perspective and also reviewed previously published data on satisfaction with a less gastrotoxic anti-inflammatory drug, rofecoxib. A questionnaire was sent to >6000 members of the Norwegian Rheumatism Association requesting information on use and toxicity of NSAID therapy and requirements for supplementary gastroprotective and analgesic medication. The questionnaire confirmed a high incidence of NSAID use. About two-thirds of users changed brands of NSAIDs at least once, usually because of adverse effects and poor efficacy. Supplementary over-the-counter (OTC) and prescription analgesics were required by 72 and 59% of patients, respectively, while OTC and prescription gastroprotective agents to treat NSAID toxicity were required by 35 and 30%. This new patient-focused survey showed that treatment with conventional NSAIDs was unsatisfactory in terms of GI toxicity and sub-optimal pain relief. Reviewing EVA (Experience with VIOXX in Arthritis) data showed that there was a high level of approval for rofecoxib, with >80% of 74192 osteoarthritis (OA) patients expressing a preference for continuing such therapy. Preference for rofecoxib was significantly higher among patients with prior experience of conventional NSAIDs or other OA-specific medication. In EVA, the reduced GI toxicity of rofecoxib previously reported in other studies appeared to translate into a strong preference to continue this therapy in a large sample of patients. This is not surprising, given the poor satisfaction with NSAIDs highlighted by the Norwegian survey.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Patient and physician satisfaction with rofecoxib in osteoarthritis: Results of the EVA (Experience with VIOXX in Arthritis) survey

A nationwide survey was undertaken among 74192 patients with osteoarthritis (OA) and 5986 physicians (including 5265 general practitioners [GPs]) in Belgium to evaluate satisfaction with the selective cyclo-oxygenase 2 inhibitor rofecoxib (12.5 or 25 mg, given once a day for an average of 30 days). Rofecoxib was considered by patients to be a very effective treatment for OA, with satisfaction scores of good or very good in the domains of pain, mobility and general satisfaction. More than 80% of GP-treated patients expressed a wish to continue rofecoxib therapy. Preference for rofecoxib was especially strong in patients (n = 45453) who had previously been treated with conventional non-steroidal anti-inflammatory drugs (NSAIDs), notably patients who had used diclofenac, ibuprofen and nimesulide. Physicians also expressed high satisfaction with rofecoxib, with more than 80% of surveyed physicians indicating a wish to continue prescribing the drug. The results of this large survey demonstrate a clear preference for rofecoxib over conventional NSAIDs in a substantial majority of OA patients. The satisfactory pain relief and excellent gastrointestinal safety profile of rofecoxib demonstrated in earlier controlled trials are likely to have been factors in patients' preferences for rofecoxib over NSAIDs.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Distribution of salivary aquaporin-5 in Sjögren's syndrome.

CommentLetterSCOPUS: le.jinfo:eu-repo/semantics/publishe

Rheumatic manifestations due to human parvovirus B19

Human parvovirus B19 has been incriminated in the genesis of hematologic, dermatologic, neurologic, and rheumatic disorders, We report four cases in which inflammatory rheumatic manifestations developed during the course of human parvovirus B19 infection documented by the presence of IgM and IgG antibodies. There was one case each of monoarthritis, oligoarthritis, polyarthritis, and enthesitis. Three patients had a favorable outcome under nonsteroidal antiinflammatory drug therapy, and one developed reflex sympathetic dystrophy syndrome. In patients with inflammatory rheumatic manifestations that do not fit any specific diagnosis, a careful family history can provide evidence suggesting human parvovirus B19 infection, which should be confirmed by tests for IgM and IgG antibodies.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

L’atteinte d’autres organes

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