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Treatment of Rheumatoid Arthritis by Intramuscular Triamcinolone Acetonide and Triamcinolone Diacetate

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Treatment of Rheumatoid Arthritis by Intramuscular Triamcinolone Acetonide and Triamcinolone Diacetate Ann Rheum Dis: first published as 10.1136/ard.20.3.274 on 1 September 1961. Downloaded from Ann. rheum. Dis. (1961), 20, 274. TREATMENT OF RHEUMATOID ARTHRITIS BY INTRAMUSCULAR TRIAMCINOLONE ACETONIDE AND TRIAMCINOLONE DIACETATE BY JACK ZUCKNER Section on Arthritis, Department of Medicine, Saint Louis University School of Medicine and the University Hospital (Firmin Desloge Hospital), Saint Louis, Missouri The results of a study (Zuckner, 1961) evaluating least 50 per cent. improvement as determined by the the therapeutic response of intra-articularly ad- estimated composite figure. The triamcinolone steroids ministered triamcinolone acetonide* (hereafter refer- were administered in rotation for the most part. red to as TActn) and triamcinolone diacetate* Clinical evidence of toxicity was sought at each visit. Observations were made for moon facies, hirsutism, (TDac) suggested that large doses of these hormones ecchymoses, blood pressure changes, body weight, had a profound systemic effect. The injection of oedema, and other possible alterations. Laboratoryby copyright. either of these hormones in a dose of 100 mg. into procedures included urine analyses, blood counts, and a knee joint affected by rheumatoid arthritis resulted erythrocyte sedimentation rates (Westergren). These in a generalized anti-inflammatory response, includ- were performed at varying intervals, usually the day of ing improvement in other inflamed joints as well as an injection and one week later at the beginning of the that injected. This generalized improvement usually study, and less frequently afterwards. persisted for 2 to 3 weeks. These favourable Other therapeutic measures were continued without findings led to further study with these steroids, modification with the exception of orally-administered steroids. 23 patients were receiving such medication utilizing the more practical intramuscular route of when the study was instituted, and an additional three administration. patients were taking steroids orally at other times duringhttp://ard.bmj.com/ the study. In nineteen individuals the oral dose of Procedure steroid was lowered, and in ten of these it was completely The acetonide and diacetate derivatives oftriamcinolone discontinued. 28 patients were receiving gold salt were injected intramuscularly into 36 patients with therapy (gold sodium thiomalate or gold thioglucose); rheumatoid arthritis. There were 112 injections, 68 in eight of these individuals the gold was begun at the of TActn and 44 of TDac. The dose per injection was time of the first steroid injection. Twelve patients had 100 mg. These steroids were compared with hydro- already received more than 700 mg. gold salt before the first intramuscular injection of a triamcinolone cortisone acetate (FAc) given by intramuscular injection on September 24, 2021 by guest. Protected in the same patients; there were seven injections of the derivative; in two others, the total dose of gold salt was 100 mg. dose of FAc, and eleven of 500 mg. between 500 and 600 mg. at the start of the study. Patients were examined once a week at first in most The duration of observation varied; seventeen patients instances, less often later. Subjective improvement in were studied for 100 or more days, and six of these for pain and stiffness and objective evidence of tenderness, approximately one year. The remaining nineteen patients heat, swelling, range of motion, capsular thickening, were observed for an average of about 70 days each. and fluid in involved articulations were determined and an estimated composite percentage recorded. These Results signs and symptoms were evaluated at each visit. The interval between injections was usually determined by the The anti-inflammatory response to intramuscular patient's subjective response, particularly the mani- injections of triamcinolone acetonide (TActn) and festation of pain. An effort was made to maintain at triamcinolone diacetate (TDac) was satisfactory in most patients. Improvement was considered satis- factory if there was at least 50 per cent. relief of * Supplied by Lederle Laboratories Division, American Cyanamid Company, Pearl River, New York. the non-permanent clinical manifestations of the 274 Ann Rheum Dis: first published as 10.1136/ard.20.3.274 on 1 September 1961. Downloaded from INTRAMUSCULAR TRIAMCINOLONE 275 disease for a period of 7 or more days after an response (such as an obvious change in the course injection. 83 per cent. of the patients showed such of the disease or an increase in physical activity) benefit at some time during treatment with TActn were not apparent. In patients in whom suitable and 80 per cent. had similar results with Thac comparisons were made, ten derived greater benefit (Table I). When the results of individual injections from TActn, and four had more improvement were analysed, approximately 73 per cent. of from TDac. injections with either TActn or TDac were followed Patients receiving gold salts simultaneously with by a satisfactory response. The average duration intramuscular steroid therapy were divided into of improvement after an injection was 20-2 and two groups for analysis: 16 2 days for TActn and TDac respectively; the (1) Those who were either beginning gold salt maximum period of relief after an injection was therapy or who had received a total dose 69 and 75 days respectively. When these results of less than 700 mg. when intramuscular were compared with those which followed the steroid injections were started; intramuscular injection of hydrocortisone acetate (FAc) in doses of 100 and 500 mg., the latter steroid (2) Those who had a total dose greater than proved inferior (Table I). The 100-mg. dose of 700 mg. during the period of intramuscular FAc was almost completely ineffective by com- hormone administration. parison, and the 500-mg. dose gave significantly poorer results. The average duration of improve- Four patients initially in the first group (less than ment with the 500-mg. dose of FAc was 5-2 days, 700 mg.) had received enough gold salt by the end and six injections were followed either by no of the study to fall into the second group (more than improvement or by not more than 3 days of benefit. 700 mg. gold salt) making a total of sixteen patients The maximum period of relief was 17 days with this in each group. This division into two groups was 500-mg. dose. The 100-mg. dose of FAc was done to evaluate any possible effect of gold salts followed by an average of 1 1 days of improvement. on the results. The separation at the 700-mg. by copyright. total dose level was selected on the assumption that total doses greater than this would be less likely to TABLE I influence the improvement attained from one RESULTS WITH INTRAMUSCULAR INJECTIONS OF TRI- injection of steroid to the next. There were 23 AMCINOLONE ACETONIDE (TActn), TRIAMCINOLONE injections of TActn and fifteen injections of TDac DIACETATE (TDac), AND HYDROCORTISONE ACETATE in the group that received less than 700 mg. gold salt (FAc) IN PATIENTS WITH RHEUMATOID ARTHRITIS and these resulted in improvement after each intra- muscular steroid injection averaging 23-4 and 15 9 Drug.TActn TDac FAc days respectively. In the second group, there were Dose (mg.)..100 100 100 500 31 injections of TActn which resulted in an average http://ard.bmj.com/ No. of Injections .. 68 44 7 11 duration of improvement after each injection of Average Duration of Improve- 19 days, and twenty injections of TDac, followed ment (days).20-2 16*2 1*1 5*2 by improvement averaging 16 6 days. Simul- Maximum Improvement (days) 69 75 5 17 taneous treatment with gold salts apparently had no Injections with No. .. 50 32 0 4 significant effect on the results. Satisfactory i Improvement Per cent. 73 5 72-7 0 36 The average daily maintenance dose of orally administered steroids at the beginning of the study on September 24, 2021 by guest. Protected was equivalent to 7- 5 mg. triamcinolone (free alcohol form, hereafter referred to as triamcinolone). A comparison of the relative efficacy of the tri- Sixteen patients were receiving triamcinolone amcinolone derivatives in individual cases was made orally, three dexamethasone, two prednisone, and in fourteen patients who received at least two two 6-methyl prednisolone. Dosages of the latter injections each of TActn and TDac. Fewer steroids were converted to triamcinolone dosages injections in a patient were not satisfactory for for evaluation purposes, using the following dosage evaluation because of the wide variability in im- ratios: provement sometimes observed from one injection was one triamcinolone: dexamethasone: prednisone: 6-methyl prednisolone to the next. Thus, it possible for injection 4 05 4 of either of the triamcinolone steroids to give very 5 satisfactory results, and for this to be followed At the end of the period of observation, the by a very poor response to the next injection of the average daily maintenance dose was equivalent same drug. Causative factors for this variability in to 4 mg. triamcinolone. Ann Rheum Dis: first published as 10.1136/ard.20.3.274 on 1 September 1961. Downloaded from 276 ANNALS OF THE RHEUMATIC DISEASES The total daily steroid dose, that is, the daily oral dose of steroid both before and during the study. maintenance dose plus the daily intramuscular dose It is noted that not all injections resulted in similar (the latter obtained by dividing the dose of steroid reactions in the same individual. Thus, only six injected intramuscularly by the days of satisfactory out of twenty injections of TActn or TDac in four improvement) was determined at the end of the patients resulted in euphoria. In one of these study and compared with the daily oral maintenance individuals, the euphoria developed within 2 minutes dose initially. To balance the doses of TActn after an injection and was associated with a "hot" and TDac, it was assumed that these steroids when feeling in the abdomen, suggesting possible entrance given intramuscularly were equivalent mg.
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