Search

Aims: To analyse the prescription of biologics (bDMARDs) in chronic inflammatory rheumatic diseases (CIRD) from Tunisian National Health Insurance (CNAM) data and to estimate their direct costs and associated factors., Methods: One hundred and nine consecutive patients who received at least one bDMARDs during a six-month period from January to June 2022 were analysed. Clinical and therapeutic parameters as well as data related to the choice of bDMARDs were identified. Direct costs were assessed. Excess costs were considered if the monthly costs exceeded 2200 Tunisian dinars (TD) per patient., Results: The most common CIRD was axial spondylarthritis (AS) in 44% and rheumatoid arthritis (RA) in 37.6% of cases. Juvenile idiopathic arthritis represented 2.7% of cases. In Tunisia, prescribing of bDMARDs is concentrated in the coastal regions and follows the distribution of rheumatologists. Certolizumab pegol was the most prescribed agent in 45% of cases. No significant association was found between the choice of bDMARD and the characteristics of patients, CIRD or prescribers. The total monthly cost of bDMARDs was 225,535 ± 1269 TD. Overspending was significantly associated with initial high DAS28 in RA and young age and total hip replacement in AS., Conclusion: Prescription of bDMARDs in CIRD is mainly for AS and in the coastal regions of Tunisia. The burden is considerable, partly due to the high cost of biologics. Data from this study may enable public health managers to better allocate the limited resources available for patient care and to develop medico-economic strategies to reduce health care costs.

Anti-Interleukin-1 (Anti-IL-1) drugs are used to treat some chronic rheumatic diseases that can affect young people, including women of childbearing age. Two anti-IL-1 drugs are available in France: anakinra and canakinumab. Data on their use during pregnancy are still limited. Based on the published literature, we carried out a review of the use of these anti-IL-1 therapies during pregnancy: therapeutic indications, pharmacological profiles and assessment of embryonic, fetal and neonatal risks. Based on this analysis, and given the absence of any reported concern, it is possible to consider the use of these two treatments during pregnancy if the clinical situation so requires and under certain conditions. Based on the data available to date, anakinra should be preferred to canakinumab whenever possible., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Chronic inflammatory arthritis are conditioners with many drug treatments available. However, many patients still suffer from symptoms impairing their quality of life. It seems necessary to propose complementary therapies favoring patients' involvement in their management. We detail several axes: nutrition and micronutrition, physical activity, management of comorbidities such as obesity, smoking and periodontitis as well as physical therapies with cryotherapy and occupational therapy., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Patients with inflammatory rheumatologic diseases are at increased risk for infectious complications, including SARS-CoV-2, which represent one of the leading causes of death in this population. This risk is due to both the numerous comorbidities of this patient's group and the immunosuppressive therapies they receive. Vaccination reduces the incidence, complications, and mortality from infections. For patients receiving immunosuppressors, exacerbation of underlying diseases is rarely observed after immunization and only live-attenuated vaccines are contraindicated. A vaccination history and updated vaccination plan should be part of the clinical follow-up of patients with inflammatory rheumatism., Competing Interests: Axel Finckh déclare avoir reçu des fonds de recherche par Pfizer INC pour un projet de recherche initié par l’investigateur, non lié à la vaccination. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Infliximab (IFX) is a chimeric monoclonal antibody which has proven its efficacy in the treatment of inflammatory diseases. However, its efficacy can be limited by the development of anti-IFX antibodies (ATI) resulting in a therapeutic failure of IFX. ATI plasmatic monitoring is then indicated to optimize IFX treatment. The aim of this study was to validate an ELISA (enzyme linked immuno sorbent assay) method of ATI plasmatic monitoring., Methods: Assessment of performance was based on the study of correlation and concordance (Bland Altman method) of the absorbances measured by the two readers. ELISA kit validation was made by calculating the accuracy and the exactitude., Results: We collected 23 samples. Their mean age was 46 years and sex ratio M/W was 0.92. In nine cases, plasmatic AIT were positive and in 14 cases, they were not detected. Correlation between the two readers showed a correlation coefficient r 2 of 99.95%. Concordance limits of the confidence interval 95% were [-112.768%-41.425%] with a bias of -35.671%. Repeatability and reproductibility were checked by a positive control and coefficients of variation were respectively of 5.574% and 14.184%. Limits of detection and quantification were respectively of 0.046 and 0.086. The positive predictive value was 0.5 and the negative predictive value was 1. The sensitivity was 100% and the specificity was 83%., Conclusion: The assessment of the performance of the tested microplate reader and the validation of the tested ELISA kit showed good results allowing ATI routine measurement to optimize therapeutic management of patients treated by IFX.

Purpose: To report the characteristics of uveitis cases occurring while on biologic therapy or disease-modifying antirheumatic drugs (DMARDs) reported to the French national pharmacovigilance database., Methods: All the uveitis cases occurring in patients with chronic rheumatologic diseases, chronic inflammatory intestinal diseases or connective tissue diseases, while treated with DMARDs and/or biologic therapies between 2000 and 2015 and reported to the French National Pharmacovigilance Database were collected., Results: During the study period, 32 cases of uveitis were reported (15 men, 17 women). Two patients were treated with one DMARD alone, 24 with biologic therapy alone, and six with both treatments. Anterior uveitis was diagnosed in 19 patients (8 cases were bilateral); intermediate uveitis was found (unilaterally) in one patient; posterior and diffuse uveitis occurred in 5 and 2 cases respectively. Five cases were inconclusive with regard to the anatomical type of uveitis. The uveitis was of infectious origin in 5 cases: 2 toxoplasmosis, 2 herpes virus and 1 tuberculosis. In the 27 other cases, it was not possible to state whether the uveitis was associated with the underlying disease (uncontrolled) or a side effect of the biologic/DMARD treatments. The occurrence of the uveitis led to 9 switches in biologic therapy and 13 discontinuations of treatment (8 complete discontinuations, 5 discontinuations only until uveitis remission was obtained). In 4 cases, the treatments were not modified. The database does not specify the ultimate course or rheumatologic disease activity at the time of the uveitis., Conclusions: The presence of uveitis while on biologic therapy must not be taken to indicate a therapeutic failure, especially if the ocular manifestation is isolated. In the case of uveitis occurring in patients treated with biologic therapies and/or DMARDs, infectious complications should be ruled out., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Osteoarticular manifestations of Lyme disease are well known features, although a number of controversies persist. These concern both the diagnosis, in particular the interpretation of serology results and the management, notably the role of antibiotics. In the article, we review a number of issues, and strive to shed light on the current evidence based Swiss and international data., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Competing Interests: P. Quartier déclare des liens ponctuels avec AbbVie, BMS, Roche-Chugai, Novimmune, Novartis, Pfizer, Sanofi, Servier et SOBI, et avoir été pris en charge lors de congrès par AbbVie, BMS, Roche-Chugai, Novartis, Pfizer et SOBI.

From the point of view of the rheumatologist, the treatment of pain should be adjusted individually in accordance with medical principles based on the facts related to the relevant pathologies. This treatment includes conservative (medicinal and non-medicinal), interventional and surgical methods. The treatment does not just depend on the diagnosis, but also on the particular functional disability based on the ICF (International Classification of Functioning) and the level of polymorbidity. As rheumatology patients often have comorbidity, the choice of painkillers (NSAIDs, analgesics, opioids etc), immunosuppressants and physical therapy methods (physiotherapy, ergotherapy, etc) may be limited.

Tetracyclines are broad-spectrum antibiotics that interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s in the treatment of acne. More recently, their biological actions on inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism were studied. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade components of the extracellular matrix (ECM). MMPs have direct or indirect effects on the vascular endothelium and the vascular relaxation/contraction system. The therapeutic effects of tetracyclines and analogues were studied in rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis and autoimmune diseases autoimmune diseases such as rheumatoid arthritis and scleroderma. In addition, downregulation of MMP using doxycycline could be beneficial in reducing vascular dysfunction mediated by MMPs and progressive damage of the vascular wall. We review the nonantibiotic properties of doxycycline and its potential clinical applications., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)

In the last 15 years, the therapeutical options for the treatment of chronic inflammatory diseases in rheumatology have increased a lot. Nevertheless, some patients do not respond or respond partially to the current therapies--including to the biologics therapy. Tofacitinib (Xeljanz) is now on the Swiss market. It inhibits the JAK pathway. Tofacitinib--as monotherapy or with methotrexate--improves the control of rheumatoid arthritis (RA). In a comparative study, tofacitinib was as effective as adalimumab. Further, tofacitinib reduced structural damages in RA and is considered as an alternative, in case of non-response, to anti-TNF and probably to other biologics therapy. The side effects are upper respiratory tract and opportunist infections and tuberculosis. Blood count, lipids, kidney function, liver tests, CK and blood pressure have to be monitored.

Major advances have been made in the pathogenesis of rheumatoid arthritis, spondyloarthritis and connective tissue diseases, leading to new biotherapies. In rheumatoid arthritis, the discovery of anti-citrulline antibodies (ACPA, anti-citrullinatedpeptide antibodies), whose specificity is between 95% and 98% and may be present before symptom onset, allowed early diagnosis and provided new pathological insights. Studies of the role of cytokines, B cells and co-stimulation of T cells revealed novel therapeutic targets. TNF inhibitors are effective in spondyloarthritis. In lupusandSjigren'ssyndrome, genes stimulatedby IFNtypel are hyper-expressed, along with BAFF (or BLyS), a B lymphocyte-activating cytokine.

With more than 830,000 live births in France, a great number of women are concerned by a long term treatment during pregnancy and many questions revolve around appreciating medication-related risks during pregnancy. This drug exposure concerns immunosuppressive drugs for inflammatory diseases and autoimmune diseases or organ transplantation involving more and more women of childbearing age. Here we will discuss the main immunosuppressive drugs classes (from chemical treatment until biological treatment with monoclonal antibodies) used during pregnancy for indicating the risks of these therapies, with an update of their use in pregnant women and for emphasizing the points whose use during pregnancy is most likely to cause concern.

Biotherapies are recent treatments, which target molecules implicated in the pathogenesis of inflammatory diseases. In pediatric rheumatology, we use anti-TNF-alpha and abatacept in JIA patients with polyarticular involvement, whereas anti-IL-6 and anti-IL-1 blockers are efficacious in the systemic form of JIA and other auto-inflammatory conditions. These new treatments have significantly improved the control of articular and systemic inflammation and the prognosis of rheumatic diseases. Their effect and their safety on the long-term need to be assessed on large cohorts of patients. Due to the impact of these chronic illnesses on the young patient and its family, and the required specific knowledge, the care of these children should be provided by a multidisciplinary team linked to a centre of competence.

In auto-inflammatory diseases, the role of the inflammasome and the interleukine IL-1beta has recently been shown. Thus, the physiopathology of rare diseases as Cryopyrin-associated periodic syndrome (CAPS) is better understood. In the era of biologics, new treatments targeting IL-1 have been developped. Canakinumab is a fully humanized monoclonal antibody inhibiting specifically IL-1beta Clinical studies have shown its efficacy on clinical symptoms and on inflammatory markers in patients with rare diseases such as CAPS or idiopathic juvenile arthritis, but also in more common rheumatic conditions like gout. Canakinumab has been approved in Switzerland only for the treatment of CAPS. Studies evaluating its effect on cardiovascular diseases are ongoing.

Anti-TNFα treatments have modified the medical care, the course and the quality of life of the patients with autoimmune rheumatic, cutaneous or bowel inflammatory diseases. On the other hand, these treatments may have potential severe side effects during pregnancy (congenital malformations, fetal infections). Actually, many pregnancies have been reported during anti-TNFα exposures, with good maternal and neonatal outcomes. The introduction or the discontinuation of these treatments will always have to be discussed with the specialist of the chronic disease and, ideally, during a preconceptional counselling. In gynecology, anti-TNFα drugs may offer a new safe and effective approach to treating patients with recurrent miscarriages or unexplained or failed in vitro fertilization cycles. On the other hand, these treatments significantly increase the risk for serious infections or viral reactivations and may promote gynaecological malignancies. An adapted gynaecological survey is necessary., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Inflammatory rheumatic disorders are related to different pathophysiological mechanisms and, hence, their therapeutic management varies according to the underlying disease. Crystal-induced arthritis is characterized by its almost specific responsiveness to colchicine. Regarding ankylosing spondylitis, non steroidal anti-inflammatory drugs (NSAIDs) and TNF blockers are the cornerstones of pharmacological intervention whereas oral corticosteroids at conventional doses are of little value, if any. Conversely, corticosteroids are the drug of choice to treat polymyalgia rheumatica. Furthermore, low-dose corticosteroids were shown to be more effective than NSAIDs in patients with rheumatoid arthritis (RA). However, the main goal being to achieve remission, disease-modifying antirheumatic drugs, either synthetic, especially methotrexate, and/or biologic, such as TNF inhibitors, have a major role in the management of RA. Finally, enhanced understanding of molecular pathogenesis of inflammatory disorders may help to find out how to best target available drugs to right individuals in the future., (© 2011 Société Française de Pharmacologie et de Thérapeutique.)

Anti-TNF alpha are immunomodulatory treatments prescribed for some rheumatologic inflammatory diseases (ex: spondylarthropathy, rheumatoid polyarthritis). The randomised studies suggested that anti-TNF alpha therapy is associated with an overall risk of infectious diseases. The results of the observational studies are more reassuring. In this article, we will describe some results of theses studies and propose some practical recommendations in use of the anti-TNF alpha therapy.

Aim: To determine the post-marketing safety profile of avocado-soybean unsaponifiables since their commercialization in France until 2008., Methods: We used data provided by French spontaneous reporting system via the network of National Pharmacovigilance centres. We analysed all suspected adverse drug reactions (ADRs) concerning avocado-soybean unsaponifiables (ASU) reported between 1978 and 2008 and notified in the French Pharmacovigilance Database., Results: We kept 117 ADRs concerning 117 patients (mean age 65.5 years, 72% female). ADRs (35.9%) were "serious" (resulted in hospitalisation or prolonged it). No death was reported. In most of cases, causality of ASU was "possible" and others drugs were also suspected. The most frequently reported ADRs were cutaneous (32.5% of all ADRs, with eczemas or urticaria), hepatic (16.2%, mostly hepatocellular injuries) and gastrointestinal (12%, with 9 cases of colitis and/or diarrhea) ADRs. In these cases, dechallenge of ASU allowed rapid regression of symptoms. Others significant ADRs were coagulation and platelet (6.8%), neurological (6%) and metabolic or nutritional (4.3%) disorders., Discussion-Conclusion: This Pharmacovigilance analysis of ASU notified since their commercialisation in France highlights the diversity of ADRs with several class-organ involved. Cutaneous, hepatic and gastro-intestinal disorders were the most frequently reported ADRs. Since ASU is largely prescribed in France, incidence of their ADRs seems to be "very rare" (although we did not take into account the part of under-notification). These safety data should be discussed in the light of the poor expected clinical benefit of ASU in rheumatology (low "Service Medical Rendu") or in stomatology (insufficient "Service Medical Rendu")., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

The aim of this study is to determine the safety of commonly prescribed antirheumatic drugs at childbearing age, in pregnancy and lactation, through systematic literature review. Patients who take cytotoxic drugs should be informed of the risks of impared fertility. During pregnancy, non steroidal anti-inflammatory drugs (NSAIDs) can be safely administered until gestational week 32. Acetaminophen and low to moderate doses of corticosteroids are safe. Among, the disease-modifying agents, antimalarial agents, sulfasalazine, azathioprine and ciclosporin are compatible with pregnancy, and can be administered until birth. Paracetamol, prednison, antimalarial agents, sulfasalazine and most NSAIDs can safely be used by lactating mothers. To ensure a favourable outcome for both the mother and the child, the pregnancy should be planned, started during a period of disease stability, monitored closely and treated as needed.

The termPneumocystis carinii is now reserved for the animal form of the disease, for humans Pneumocystis jiroveci is appropriated. Incidence of pneumocystis pneumonia (PCP) among patients with systemic rheumatic diseases varies from 0.2% for rheumatoid arthritis to up 12% for Wegener's granulomatosis. Clinical and radiological presentation of pneumocystis pneumonia among non-VIH patients is often difficult to diagnose and the installation can be abrupt. Most of cases of PCP occur during the first 3 months following the beginning of immunosuppressant agents. Mortality during PCP is high with an average of 40% of death, rising 60% in case of mechanical ventilation. Prophylaxis of PCP is needed (without support by randomised studies) for patients with Wegener's granulomatosis, in case of cyclophosphamide or high-dose of methotrexate use except for rheumatoid patients, if a simultaneous treatment by corticosteroids and immunosuppressant agent is required, if a prolonged corticosteroid treatment (> 2 months) is used with dose of prednisone-equivalent > 16mg per day or > 20mg per day > 1month associated with one or more risk factors of PCP among advanced age, denutrition or deep lymphopenia. The best prophylaxis of PCP is cotrimoxazole.

The incidence of tuberculosis among patients with systemic rheumatic diseases is much higher than in the general population (the risk is multiplied by 5 to 15 in patients with systemic lupus erythematosus). Reactivation of a latent tuberculosis is frequent, as assessed by the short delay of occurrence after a systemic rheumatic disease has been diagnosed. Besides immunosuppression induced by the underlying disease, the role of glucocorticoids and of immunosuppressive therapy including biotherapies using TNF antagonists must be underlined. Tuberculosis in such patients frequently presents as extrapulmonary or disseminated disease. A screening of tuberculosis is recommended before anti-TNF therapy, and includes previous history questioning, chest X ray, tuberculin skin test with 5 international units of tuberculin. Immunological methods of tuberculosis detection are under evaluation in these patients. If a latent tuberculosis infection is diagnosed, a specific tuberculosis chemoprophylaxis, started at least 3 weeks before initiation of TNF antagonists, has allowed to reduce the occurrence of anti-TNF-associated tuberculosis in patients living in Europe and North America. The screening strategies for tuberculosis should probably be extended in all patients with systemic rheumatic diseases receiving glucocorticoids and/or immunosuppressive therapy.

Breastfeeding is often contraindicated when drugs are prescribed for a chronic maternal disease. Many of the restrictions are based on theoretical concerns only and may be excessively cautious. An updated review is mandatory. Many antirheumatic drugs can be safely used during lactation: nonsteroidal anti-inflammatory drugs, corticosteroids, sulfasalazine, antimalarial agents. Doubt remains about safety of cochicine or dapsone. Expert opinions still diverge but move on in favor the use of azathioprine, ciclosporin, and even methotrexate. Leflunomide, mycophenolate mofetil and cyclophosphamide are contraindicated. No conclusion can be reached regarding anti-TNF-alpha and rituximab. Current knowledge about drug transfer in breast-milk and cumulative empirical data have expanded the possibilities to allow breastfeeding when the mother is treated with antirheumatic medications. The data provided by pharmaceutical industry should not be the only source of the physician's information in the risk assessment.

Objective: the aim of this study is to determine the clinical characteristics of drug-induced agranulocytosis in rheumatology., Patients and Method: it is a retrospective monocentric study, including all cases of rheumatologic drug-induced agranulocytosis followed between January 1985 and December 2005., Results: eight female and 4 men, mean age 62.5 years (range: 17-79), were included in the present study. The causative drugs were: anti-inflammatory agents (n=5, 41.6%), methotrexate (n=3, 25%), sulfasalazine (n=2, 16.6%), noramidopyrine (n=1) and dapsone (n=1). Main clinical features included infectious disorders in 9 cases (75%) with 4 cases of septicemia (33.3%) and 2 cases of septic shock (16.6%). The mean neutrophils count was 0.132 x 10(9)/L (range, 0-0.4). Outcome was favorable in 11 patients (91.6%). One patient died of septic complications., Conclusion: in rheumatology, drug-induced agranulocytosis is a rare but life-threatening disorder.

Analysis of national data from the health ministry programme of reduction of the cardiovascular risks (2002-2005) shows a high frequency of cardiovascular disease and cardiovascular risk factors in the general population. It is of interest to analyse these data in relation to the practice of rheumatology. In addition, the frequency of cardiovascular pathologies is higher in patients with rheumatoid arthritis and spondylarthropothy. These notions are also very important since these two populations are often treated with non-steroidal anti-inflammatory drugs for a long duration. General knowledge shown in this article concerning the cardiovascular risk factors and co-morbidities in the patients with rheumatic pathologies allows, within the context of a therapeutic decisional strategy in rheumatology, a better estimation of the individual benefit/risk ratio of each prescription and more particularly that of non-steroidal anti-inflammatory drugs.

Analysis of national data from the health ministry programme of reduction of the cardiovascular risks (2002-2005) shows a high frequency of cardiovascular disease and cardiovascular risk factors in the general population. It is of interest to analyse these data in relation to the practice of rheumatology. In addition, the frequency of cardiovascular pathologies is higher in patients with rheumatoid arthritis and spondylarthropathy. These notions are also very important since these two populations are often treated with non-steroidal anti-inflammatory drugs for a long duration. General knowledge shown in this article concerning the cardiovascular risk factors and co-morbidities in the patients with rheumatic pathologies allows, within the context of a therapeutic decisional strategy in rheumatology, a better estimation of the individual benefit/risk ratio of each prescription and more particularly that of non-steroidal anti-inflammatory drugs.

The cardiovascular impact of the non-steroidal anti-inflammatory drugs and the higher cardiovascular mortality during treatment of inflammatory rheumatism impose a rigorous evaluation of the cardiovascular risk of rheumatic patients. Large epidemiological studies have identified risk factors for cardiovascular diseases such as the age, male gender, family history (infarct, stroke), tobacco consumption, systolic arterial pressure, renal insufficiency, hypercholesterolemia, diabetes mellitis, sedentariness, obesity and "electric" ventricular hypertrophy. Some equations make it possible to evaluate the absolute cardiovascular risk at the individual level, which corresponds to the onset risk of a stroke in the 10 years to come in a subject according to the number and importance of each of his risk factors. It has been demonstrated that the correction of one or more risk factors reduce the overall cardiovascular risk justifying the strategies for evaluating this risk to define therapeutic intervention thresholds. The impact of a long-term anti-inflammatory treatment or an inflammatory disease such as rheumatoid arthritis has not been the subject of specific epidemiological study allowing these elements to be included in an equation of the estimation of the cardiovascular risk. However, the introduction of on anti-inflammatory treatment, likely to increase the cardiovascular risk of a patient, certainly justifies an evaluation of the absolute cardiovascular risk.

Nabumetone's position as one of the most commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) in the world today is based upon over a decade of clinical experience. The popularity of this drug lies in both its unique pharmacokinetic profile and special safety features in pharmacodynamic terms. This nonacidic prodrug with an active 6-methoxy-2-naphthylacetic acid (6-MNA) metabolite has COX-2 preferential features and is also devoid of enterohepatic recirculation. It is felt that these characteristics have provided the basis for its unique long term tolerability, documented in various at-risk osteoarthritis and rheumatoid arthritis populations. The excellent tolerability of nabumetone and its 24-hour half-life, which provides the advantages of a once-daily dosage regimen, make it uniquely suitable for long term anti-inflammatory therapy in arthritis. The tolerability profile of nabumetone has also demonstrated clear cost-effectiveness advantages, as confirmed by comparative and epidemiological studies. Selective COX-2 NSAIDs are likely to prove more expensive because of the increasing costs and demands of clinical research prior to FDA approval. These higher costs may limit and influence patient access, depending on the healthcare delivery system, and many years of experience will be required to document the putative tolerability advantages of these newer COX-2 inhibitor agents. In the meantime, it is comforting that nabumetone has established such an advantageous tolerability profile together with acknowledged efficacy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have become one of the most commonly used drug classes. However, the gastrointestinal adverse effects, including ulcers, perforation and bleeding, constitute a major problem, although the risk of their occurrence appears to vary according to the different classical NSAIDs used. These drugs inhibit the key enzyme in prostaglandin biosynthesis, cyclo-oxygenase or COX. COX exists in 2 isomeric forms, COX-1 and COX-2, which are inhibited to different extents by the classical NSAIDs. COX-1 leads, for example, to the production of prostaglandins that are cytoprotective for the gastric mucosa. COX-2 is inducible in a number of cells by pro-inflammatory stimuli. The selective COX concept predicts that inhibition of COX-1 may result in gastrointestinal adverse effects, whereas inhibition of COX-2 may underlie the anti-inflammatory actions of NSAIDs. These observations have led to the development of new drugs with high inhibitory potency for COX-2 and low potency for COX-1. These selective COX-2 inhibitors appear to be promising in animal models and endoscopic studies in humans. If large clinical and epidemiological studies confirm that (i) selective COX-2 inhibitors are as effective as classical NSAIDs, (ii) the frequency of severe gastrointestinal complications is considerably reduced with these new drugs, and (iii) no unexpected complications of selective COX-2 inhibition are detected, then selective COX-2 inhibitors will prove to be a significant advance in the treatment of patients with rheumatic diseases.

Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) of the 2,6-disubstituted naphthylalkanone class. It is a prodrug metabolised to an active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), which preferentially inhibits cyclo-oxygenase-2 (COX-2) and has both anti-inflammatory and analgesic properties. The efficacy of nabumetone is comparable to that of other NSAIDs currently marketed in France for the treatment of rheumatoid arthritis and osteoarthritis. Nabumetone is metabolised to 6-MNA by extensive first-pass metabolism. This active metabolite is subsequently conjugated and excreted in urine. 6-MNA does not undergo enterohepatic recirculation, which may have implications for comparative gastrointestinal toxicity. Substantial concentrations of 6-MNA are achieved and maintained in synovial fluid, which is close to the proposed site of action in chronic arthropathies. The long plasma half-life of 6-MNA (20 to 24 hours) and its persistence in synovial fluid facilitate a once-daily dosage regimen. Nabumetone compares favourably with other NSAIDs with respect to its renal and gastrointestinal adverse effect profile, although increased clinical vigilance of drug-related adverse events relating to these organ systems is still recommended. In addition, in vitro experiments have shown this drug to have a good cartilage tolerability profile. Whether nabumetone has clinical utility in cardiovascular disorders remains to be determined. The unique pharmacokinetic and pharmacodynamic properties of nabumetone make it a welcome addition to the growing arsenal of drugs used in the treatment of chronic arthropathies. There may be clinical advantages in terms of the relative tolerability profile of nabumetone, given that this drug has a low COX-2/COX-1 ratio compared with other nonselective NSAIDs.

Introduction: As short-term corticosteroid therapy is widely used in clinical practice, it is important to determine its precise indications and limits of use., Current Knowledge and Key Points: Duration of short-term corticosteroid therapy is arbitrarily considered to be up to 21 days. Anti-inflammatory, antiproliferative or analgesic actions represent the main pharmacological features of steroids. They are related to the interactions of steroids with cytokines and immune cells. Results of randomized double-blind and uncontrolled clinical studies were included in this review. Furthermore, clearly demonstrated results that were obtained more particularly in neurology, otorhinolaryngology, pneumology, infectious diseases, rheumatologic and traumatic processes are summarized., Future Prospects and Projects: Indications for short-term corticosteroid therapy are well established. However, further clinical studies are required, as current prescription of corticosteroid is still empirical in the management of most diseases.

We report the case of a 75-year-old woman who was hospitalized for serum aminotransferase elevation. She had taken 1 g/d of salicylate therapy (Aspegic 1000) for 5 years, clorazepate for 10 years, naftidrofuryl for 8 months and quinapril for 3 months. Liver histology showed cirrhosis and granulomatous hepatitis. Discontinuation of salicylate therapy resulted in normalization of liver tests, although other drug administration was pursued. This observation suggests that salicylate therapy can induce cirrhosis.

Five adults had inflammatory rheumatic disorders 6 to 20 years before the diagnosis of coeliac disease. It is known that joint inflammation occurs in certain patients with adult coeliac sprue who develop either a specific inflammatory rheumatic disease or an atypical progressive polyarthropathy, sometimes as the first manifestation of the intestinal disorder. The diagnosis of adult coeliac sprue should be entertained in these cases even in absence of major digestive disorders or malabsorption. IgA anti-reticulin antibodies and atrophy of the duodenojejunal villosities are the best indicators for diagnosis. There are two important reasons for making the diagnosis of "asymptomatic adult coeliac sprue". First a gluten-free diet can improve or even cure the inflammatory joint disease, a rare situation which emphasizes the causal relationship between these two diseases. Second, the risk of developing lymphoma (especially in the small bowel) is apparently lower in patients on gluten-free diet. Pathogenesis is unclear. Frequently the two autoimmune disorders simply appear to coincide in the same patient; more rarely, arthritis is a symptom of coeliac disease. The immunological mechanisms probably begin when antigens cross an excessively permeable intestinal mucosa.

Vitamin B1, B6 and B12 are frequently prescribed in rheumatic diseases as analgesic drugs. If some fundamental data suggest their analgesic potential, especially in animal models, there are very few clinical trials in human demonstrating their efficacy in rheumatology. Looking at these data from the literature, we should reconsider our prescription of vitamin B.

An insufficient compliance is regularly observed in 30% of outpatients. In chronic rheumatic diseases such as rheumatoid arthritis a poor compliance is often associated with alleviation of symptoms whereas symptomatic patients tend to take their medication more regularly. Drug abuse, mainly corticosteroids, can often not be avoided. The latter may 'particularly in women' lead to osteoporosis with subsequent fractures. In patients with fibrositis compliance is often a poor because of digestive problems associated with NSAIDs and the bad response to drugs and adjuvant therapies.