Rheumatoid arthritis treatment glucocorticoids again from behind the scenes to the front of the stage

the middle of the last century, glucocorticoids have been used to treat rheumatoid arthritis (RA), which is considered a "magic cure" for RAHowever, with the growing awareness of the adverse effects of glucocorticoids and the use of new therapeutic drugs (or new drugs), glucocorticoids became the second- and third-line drugs used to treat RA after the 1980sIn the "pyramid" program of RA treatment, "non-steroidal anti-inflammatory drugs (NSAID)," "proper exercise", "patient education" as the initial treatment measures, is the bottom of the pyramid, for which patients gradually add penicillin, gold preparation, and then the next layer is cyclophosphamide (CTX), methotrexate (MTX), at the top of the pyramid is experimental drugs and glucocorticoidsThus, clinicians have taken a very conservative attitude towards the treatment of RA with glucocorticoidsClinically, glucocorticoids are used only for active arthritis accompanied by fever, anemia and other systemic symptoms, severe internal stress, as well as NSAID, relieve the condition of anti-rheumatoid drugs (DMARD) and other conventional treatment drugs are not effective patientsShort-term (not more than 3 months) and small-dose treatment (not more than 10 mg daily dose) are advocated in drug dosage and course selectionIn recent years, there has been a new understanding of small doses of glucocorticoid therapy RA, and new expectations for its efficacy and improvement of RA prognosis, which was fully reflected at the 2007 EULAR Annual MeetingGlucocorticoids are also a type of DMARD
Professor Boers of the Netherlands boldly suggested that glucocorticoids are also a type of DMARDHe and his colleagues analyzed the results of the studies reported between 1955 and 2005, and the final 15 studies met the inclusion
criteria(all of which were for early RA (2 years of disease), the cumulative dose of pernith (or equivalent doses of other glucocorticoids) in the first year was 2,300 mg (270 to 5800 mg), while patients were taking other DMARD treatments at the same timeIn a study called COBRA, the researchers treated a larger dose of persinisone with a gradual reduction in doses, combining MTX with SASPThe results showed that patients with the combined drug groupdiseaseprogresses slower than those in the single SASP group After 5 years of follow-up, the number of patients in the combined drug group who progressed their illness each year was only half that of the single SASP group However, the therapeutic effects of MTX were not fully discussed in this study In the study of Choy at the Royal College, the researchers divided 467 patients with new hair RA patients with a course of disease shorter than 2 years into four groups: MTX group, MTX-cyclosporine Group A, MTX-Pernisone group, MTX-per-spone-cyclosporine Group, MTX dose of 15 mg/week; Take for 9 months, 1 to 2 weeks for 60 mg/day, after gradual reduction, 7 to 28 weeks dose of 7.5 mg/ day, and then gradually withdraw the drug, the 35th week of withdrawal; Patients were examined once every 6 months for 2 consecutive years, followed by whether there was a new bone damage The results showed that the incidence of bone damage in patients in the MTX-per-per-paper-perssinium group or mTX-cyclosporine A group was only half that of the single MTX group This suggests that MTX co-use of pernison reduces bone erosion and has a continuous effect (follow-up period to 1 year after the deactivation of perison) The researchers believe that in early RA patients, there is a "window of opportunity" for treatment, and if combined drugs in the early stages of this period can reduce the incidence of bone erosion and have a lasting effect But the researchers also point out that while MTX co-use of perniscansone can reduce bone erosion, improving the quality of life of patients requires two traditional DMARDs because of their synergy The study of adverse reactions has been a concern for physicians the of adverse reactions caused by hormones, but current systematic evaluation scans show that the use of small doses of persinisone (daily dose of 7.5 mg) does not cause many of the adverse reactions that people are concerned about Adverse reactions caused by glucocorticoids are closely related to doses, and some adverse reactions, such as bone necrosis, hormonal myopathy, hormonal psychosis and pancreatitis, are rare in small doses of hormone therapy Osteoporosis is a very clear adverse reaction to the use of hormones Although osteoporosis is closely related to fractures and treatments, there is currently evidence that even 2.5 mg of pernison per day increases the risk of bone loss and fractures Studies have suggested that in patients taking glucocorticoids, even if bone density is higher, fractures are more likely to occur, suggesting that glucocorticoid-related fractures may not be entirely associated with decreased bone density Happily, hormone-related osteoporosis can now be effectively prevented In order to further increase the safety and efficacy of glucocorticoids, in recent years, people have continuously improved the varieties and formulations of glucocorticoids The more ideal of these are nitrosoglucoticoids and selective glucocorticoid receptor agonists Another strategy is to change the dosage form and process of glucocorticoids so that their release characteristics are more in line with the body's circadian rhythms A new perison-controlled release tablet has now entered Phase III clinical trials, which are taken before bedtime and are released gradually four hours after taking the drug, making it easier to take than traditional ostonic glucocorticoids The clinical trial was reported by Buttgereit in Germany, where 288 RA patients were randomly divided into two groups, one using controlled penisone and the other using a traditional penisone preparation, all with a dose of 3 to 10 mg/day, with an observation period of 3 months, recording laboratory and clinical indicators related to disease activity The results showed that the improvement of morning stiffness in patients in the controlled release tablet group at 2 weeks was better than that of the general preparation group by 10% By March after drug use, the advantage was even more pronounced, with the slow release preparation group improving by 22.7%, while the general formulation group improved by only 0.4% The IL-6 level, which was the marker of inflammatory reaction, decreased by 30% in the slow release preparation group, while there was no change in the general formulation group In order to prevent hormone-related osteoporosis, clinically commonly used calcium preparations, active vitamin D3, disphosphate to preventive treatment A study presented at this annual meeting showed that 1,25-dihydroxyvitamin D3 analogues inhibit the production of pre-inflammatory cytokine (pre-destructive cytokine) IL-17 and can resist the inhibition of glucocorticoids against inflammatory cytokines (anti-destroycyfactor) IL-4 Therefore, the 1,25-dihydroxyvitamin D3 analogue may increase the anti-inflammatory effect of glucocorticoids by regulating the immune system, while reducing bone loss caused by glucocorticoids In short, experimental and clinical studies in recent years have strongly suggested that the role, status and long-term efficacy of glucocorticoids in RA therapy deserve our attention (Yu Hejian)