JAK inhibitors in refractory juvenile rheumatic diseases: Efficacy, tolerance and type-I interferon profiling, a single center retrospective study.

Objectives: - Janus Kinase inhibitors (JAKi) are a new class of drugs available for pediatric rheumatic diseases. This study aimed to describe the safety and effectiveness of JAKi in these diseases, with a focus on longitudinal interferon-stimulated genes (ISG) assessment.

Methods: - We present a single-center retrospective study of children with refractory pediatric rheumatic diseases including connective tissue diseases, monogenic type I interferonopathies or juvenile idiopathic arthritis, receiving JAKi.

[Enhancing awareness of the modalities in the management of chronic inflammatory diseases].

From an epidemiologic point of view, the incidence of rheumatoid arthritis in the French regions we studied appears relatively stable and about the same as the prevalence of rheumatoid spondylosis. The incidence of Crohn's disease, among the chronic inflammatory bowel diseases, is currently increasing. Treatment for rheumatoid arthritis, other than symptomatic and maintenance treatments, now includes various specific forms of "biotherapy".

[Assessment of a topical NSAIDs in the treatment of pain and inflammation. The example of Flector Plaster, a local bioadhesive plaster containing diclofenac epolamine].

ADVANTAGES AND INCONVENIENCIES OF TRANSDERMAL SYSTEMS: Regarding the advantages, one notes the reduction or even suppression of the gastro-intenstinal disorders related to the oral administration of non-steroidal anti-inflammatories (NSAIDs), the absence of first pass hepatic effect and the better control of the quantities administered of a strong acting drug. Regarding the inconveniencies, one should bear in mind the impossibility of administering or the diffusion of high doses of irritant or sensitizing molecules on the skin. A preparation for application on the skin must be both hydrophilic and lipophilic, with great solubility in water and affinity for the lipids, as is the case with diclofenac epolamine.

[Proof of the pharmacodynamic activity of Flector Plaster in healthy volunteers and patients suffering from osteo-arthritis of the knee].

STUDY OF HEALTHY VOLUNTEERS: This double blind study (bioadhesive plaster of diclofenac epolamine versus placebo), showed that the application of diclofenac epolamine for 24 hours induced a selective hypoanalgesic effect on the muscle, proportional to the degree of hypersensitivity to the pain observed in baseline conditions. The enhanced effect on the hyperalgic muscle can be explained by the direct impact of the active ingredient on the nociceptors and/or its inhibiting effect on the local production of prostaglandins. STUDY OF PATIENTS SUFFERING FROM BILATERAL OSTEO-ARTHRITIS OF THE KNEE: In a 24 hour trial of the treatment (bioadhesive plaster impregnated with diclofenac epolamine (Flector Plaster) versus placebo), the active treatment had a significant impact on the spontaneous pain during rest that was enhanced during mouvement.

[Osteoarthritis, disability, travel and recreational activities: comments from physicians and travel specialists].

IMPACT OF DISABILITY: A survey of general practitioners, rheumatology specialists, and tourism specialists conducted by NEGMA-LERADS Laboratories demonstrated that subjects with osteoarthritis avoid vacation trips more readily than recreational activities. VACATION TRIPS ARE STILL POSSIBLE: Certain tourism organisms have nevertheless developed specialized services for disabled persons. Special emphasis is placed on adequate preparation before the vacation trip.

[Management of patients with osteoarthritis: contribution and limitations of clinical and radiological follow-up].

Unlabelled: THE RHEUMATOLOGIST'S CONTRIBUTION: Several data favor regular referral of patients with osteoarthritis to rheumatology specialists and/or continued follow-up by general practitioners. Important elements include difficulties in establishing the initial diagnosis, technical procedures, and individual adaptation of drugs and/or non-drug treatments.

Follow-up: The different elements of follow-up include the patient's overall opinion concerning disease progression, pain assessment, control of body weight and body mass index, evaluation of joint movement, analysis of treatment efficacy and tolerance, and radiological surveillance to evaluate the rate of progression of joint space narrowing.

[Biological markers of osteoarthritis: data from the ECHODIAH cohort].

CORRELATIONS OF BIOLOGICAL MARKERS: Ten biological markers collected from blood or urine were analysed in the ECHODIAH cohort (patients with hip OA with a 3 Years follow up). In multivariate analysis, after adjustment for age, gender, and body mass index, some markers were found to be significantly correlated with clinical and radiological parameters. C-telopeptide of type II collagen (CTX-II) was correlated with pain, functional impairment, joint space narrowing, and subchondral sclerosis.

[Mechanisms of action of diacerein, the first inhibitor of interleukin-1 in osteoarthritis].

DEGRADATION AND REPAIR: Osteoarthritis generally occurs in a context of an overloaded normal cartilage matrix or normal loading of a vulnerable cartilage matrix. Interleukin-1 appears to be principally indicated in degradation phenomena while transforming growth factor (TGFbeta) is mainly implicated in phenomena of excessive synovial and chondrocyte repair observed at the same time as degradation. MECHANISMS OF ACTION OF DIACEREIN: Diacerein is a slow acting symptomatic treatment of osteoarthritis which has demonstrated efficacy on functional manifestations of osteoarthritis and on the structural component.

[Total hip arthroplasty indication, evaluation criteria for structure modifying trials. Lessons from the ECHODIAH and PHARE studies].

RADIOLOGICAL EVALUATION CRITERIA: To date, outcome of therapeutic trials examining structure modifying treatments has been basically assessed with repeated measurement of joint spaces on plain x-rays. In the ECHODIAH study, these measurements demonstrated an advantage in favor of treatment with diacerein. Magnetic resonance imaging has not been validated for therapeutic trials.

[COART France 2003 report on new socioeconomic data on osteoarthritis in France].

RISING COSTS: According to the first evaluation of the socioeconomic impact of osteoarthritis in France conducted in 1993, the estimated annual cost was slightly less than one billion euros. In 2003, the annual cost was approximately 1.8 billion euros.

[rHU-EPO in cancer patients. Target or wider use?].

THE DEBATE: Although some believe that rHu-EPO should not be widely used in malignant affections, others think that because of the varied impact of these anaemia, its wider use should be recommended. FOR A TARGET USE: Various observations (influence of the degree of extension of the myelomas to the skeleton and response to specific treatment in the case of myeloma, whatever the haemoglobin concentration, degree of prevention of rHu-EPO chemo-induced anaemia) are in favour of its use in selected patients. FOR A WIDER USE: The benefits of treatment with rHu-EPO are not limited to the symptomatology of anaemia but extend to its potential complications in the most fragile patients.

[The problem of acquired aplastic anaemia].

PURE RED CELL APLASIA: Designated by the acronym PRCA or the term erythroblastopenia, pure red cell aplasia is characterised by severe anaemia with reticulocytopenia. It may occur in acute form induced by infectious agents, following drug toxicity or transplantation of allogeneic haematopoietic cells, associated with autoimmune haemolytic anaemia. The chronic form is rarely constitutional but can be acquired and is usually associated with blood or idiopathic diseases.

[The benefits of treatment with recombinant human erythropoietin in cancer patients].

IMPROVED QUALITY OF LIFE WITH EPOETIN BETA: In a study against a placebo, there was evidence that the quality of life scores were significantly improved in patients treated with epoetin beta, whether they exhibited a solid tumour or a malignant lymphoma. The same was noted in children with cancer exhibiting severe neoplasia and treated with chemotherapy. The efficacy and tolerance to treatment were equivalent, whatever the administration regimen.

[The basis of treatment with recombinant human erythropoietin].

A line of transgenic mice overexpressing erythropoietin was created. These mice retained their capacity to reduce their gastro-intestinal absorption of iron and to regulate the changes in their iron metabolism and they could serve as a model for the in vivo study of iron homeostasis and erythropoiesis. NEW INDICATIONS FOR RECOMBINANT HUMAN ERYTHROPOIETIN: After chronic terminal kidney failure, the treatment of chronic dialysed kidney failure patients and patients treated with azathioprine or patients having undergone surgery and requiring transfusion, other indications have been proposed.