rimexolone and Arthritis--Rheumatoid

A short cut review was carried out to establish whether intra-articular corticosteroid injections were effective at reducing pain in patients with acute rheumatoid monoarthritis. Altogether 215 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Humans; Injections, Intra-Articular; Pregnadienes; Treatment Outcome

Twenty patients with classical or definite rheumatoid arthritis received one intra-articular injection of 40, 80, 120, 160 or 200 mg rimexolone (Org 6216) into one knee joint. Rimexolone was well tolerated and the incidence of side-effects was low. A beneficial effect was sustained over the study period of 94 days and a long-lasting effect was observed in 84% of the patients after one year and in 79% after 2 years. Safety parameters remained unaffected. Individual changes in adrenal response to ACTH and morning cortisol levels did not correlate with the dose or with serum levels of rimexolone. Rimexolone showed linear kinetics. The mean residence time in the intra-articular depot was 44 days (SD +/- 53) with a median of 26 days. Ninety percent was absorbed after 4 months. Outside the intra-articular depot the mean residence time was less than 0.1 days.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Drug Tolerance; Female; Humans; Hydrocortisone; Injections, Intra-Articular; Knee Joint; Male; Middle Aged; Pituitary-Adrenal System; Pregnadienes; Synovitis

One-hundred and thirty-seven patients with classical or definite rheumatoid arthritis, involving at least one knee joint, were randomly allocated to a single intra-articular injection of 10, 20 or 40 mg of rimexolone (Org 6216) or placebo. The follow-up period was 84 days, during which clinical and laboratory assessments were done. Clinical improvement of the treated knee joint was measured by the following variables: pain, tenderness, morning stiffness, swelling, range of movement and walking ability. Placebo response was considerable. However, clinical improvement with rimexolone at 20 mg and 40 mg was significantly superior to placebo for most of the variables, whilst with the 10 mg dose only reduction of tenderness was significantly superior. The duration of improvement was longest with 40 mg of rimexolone. One single, intra-articular injection of this dose into the affected knee joint provided significant reduction in pain, tenderness and stiffness and improved the range of movement and walking ability for a period of 8 to 12 weeks.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Intra-Articular; Knee Joint; Male; Middle Aged; Pregnadienes

The pharmacokinetics of rimexolone were investigated after intra-articular injection into the knee joints of patients with rheumatoid arthritis. After a single dose of 40 mg rimexolone the drug could be detected in plasma over 3 months. The suspension dissolves in the synovia very slowly and provides a sustained release of the steroid in the joint. Pharmacokinetic analysis was performed on the assumption that the disposition of rimexolone after intra-articular administration is absorption limited ("flip-flop-case"). Dose linearity was studied in a range from 40 to 200 mg. Total body clearance averaged 106 L/h and was independent of dose. The mean residence time of rimexolone in the knee joint is very long and averaged 25 days. It could be shown that the mean residence time of different glucocorticoids correlates well with the duration of their clinical effectiveness.

Topics: Arthritis, Rheumatoid; Delayed-Action Preparations; Female; Humans; Injections, Intra-Articular; Knee Joint; Male; Metabolic Clearance Rate; Pregnadienes; Time Factors