Ann. rheum. Dis. (1964), 23, 456.

INTRAMUSCULAR ADMINISTRATION OF STEROIDSIN TREATMENT OF RHEUMATOID ARTHRITIS

BY

JACK ZUCKNER, JAMAL UDDIN, AND ROBERT H. RAMSEYSection on Arthritis, Department of Internal Medicine, St. Louis University School of Medicine,

St. Louis, Missouri

In a preliminary report (Zuckner, 1961) on intra-muscular steroid therapy in patients with rheumatoidarthritis, results of approximately 100 injections oftriamcinolone acetonide (hereafter referred to asTACTN)* and triamcinolone diacetate (or TDAC)twere described. The responses to this method ofsteroid administration were satisfactory in mostcases, and compared favourably with those followingthe oral administration of steroids. In about 25 percent. of cases, the anti-rheumatic effect was superior.

This study has been continued, and in the ensuing18 months another 820 injections have been evalu-ated. Other steroids were also tried for comparisonof their antirheumatic effectiveness by intra-muscular administration. These included the depotpreparation of 6-methyl prednisolone (referred toas DM)", triamcinolone acetonide tertiary-butyl-acetate (TATBA)t, and triamcinolone acetonidemonoenanthate (TM)§. The chemical formulae ofthese preparations are shown in the figure oppo-site.

ProcedureTACTN, TDAC, DM, TATBA, and TM were in-

jected intramuscularly into 86 patients with rheumatoidarthritis. These patients were classified (Table I)according to criteria of Steinbrocker, Traeger, andBatterman (1949), the majority being in Stage II, Class II.Their ages ranged from 32 to 75 years, most being in theirfifties. There were 66 females and twenty males. Theduration of disease was less than 5 years in about40 per cent. and more than 10 years in one-third of thecases. Disease activity was graded 1 to 4 plus, andapproximately 90 per cent. of the patients were consideredto have 2 or 3 plus changes at the onset of the study.

* TACTN-Supplied by E. R. Squibb & Sons, New Brunswick,New Jersey, and by Lederle Laboratories Division, AmericanCyanamid Company, Pearl River, New York.

t TDAC, TATBA, and FAC-Supplied by Lederle LaboratoriesDivision, American Cyanamid Company, Pearl River, New York.

t DM-Supplied by The Upjohn Company, Kalamazoo, Michigan.§ TM-Supplied by E. R. Squibb & Sons, New Brunswick, New

Jersey.

TABLE I

CLASSIFICATION OF PATIENTS WITH RHEUMATOIDARTHRITIS TREATED WITH INTRAMUSCULAR STEROIDS

American RheumatismAssociation Classification*

Stage ..

Class ..

* Steinbrocker, Traeger, and Batterman (1949).

There were 900 injections of 100 mg. each. Theamount of steroid injected was varied in a few individualsin an attempt to determine an optimum dose. Tenpatients received a total of eleven injections of '0 mg.TACTN and these were compared with doses of 100 mg.TACTN in the same individuals. Nine injections of140 mg. TACTN were compared with a 100-mg. dosein six cases. One hundred or more injections each ofTACTN, TDAC, and DM were administered to 53, 47,and 68 patients, respectively (Table II, opposite).Most injections (532) were of DM. A few injections

of hydrocortisone acetate (FACt) in 500-mg. doses werealso included for comparison; 22 patients received twentyor more injections; the greatest number for one patientwas 38.The different steroids were compared in individual

cases only if at least two injections of each hormone wereadministered. In this manner, two, three, four, or,occasionally, all five steroids were evaluated in the sameindividual.

Thus, it was possible to compare TACTN, for example,with TDAC in 23 cases, with DM in 22, with TM inseven, and with TATBA in ten cases. TDAC and DMwere compared with the other steroids almost as fre-quently as described for TACTN. TM and TATBAwere similarly evaluated about half as often.During the study, not all the steroids mentioned were

available at the same time. Therefore, it was not possibleto rotate all the preparations at subsequent injectiontimes in the same individual; however, the same steroidwas usually not administered twice in succession. Thisrandom variation was done deliberately in an effort tominimize interfering factors which could appear from

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INTRAMUSCULAR STEROIDS

0

CH2-O-C-CH3

H 0

HO ---OH 1

C--- O-C-CH3

TRIAMCINOLONE DIACETATE

0

ICH2-O-C-(CH2)5-CH3

C=O

TRIAMCINOLONE ACETONIDE MONOENANTHATE

TRIAMCINOLONE ACETONIDE

0 CH3I

CH2-0-C-CH2-C- CH3I I

H3 C;-0C CH3

HO ---.0

CH-'C

H,3

3

t

g j_n_s

0

ICH2_O0-C -CH3

C=O) OH

CH3TRIAMCINOLONE ACETONIDE TERTIARY BUTYLACETATE METHYLPREDNISOLONE ACETATE

Chemical composition of five steroid preparations.

TABLE II

NUMBER OF INTRAMUSCULAR INJECTIONS

Triaminoloe Tramcinlone Depot Prepara- Triamcinolone TriamcinoloneSteroid TrIAcetolode Diacitate tion of 6-Methyl Hydrocortisone Acetonide Acetonide

Monoennthate Butylacetate

Dose (mg.) .100 100 100 500 100 100

No. of Patients 53 47 68 11 18 28

Injections . . 182 100 532 11 33 53

3

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ANVNALS OF THE RHEUMATIC DISEASESone injection time to the next and which might possiblyaffect the results, such as, a spontaneous remission or anexacerbation of symptoms due to the inherent nature ofthe disease. There were, however, eighteen patients whoreceived DM as the only injectable steroid over a periodof time averaging 18 months for each. Three hundredand seventy-four injections of DM were administered tothis group, averaging about 21 injections per patient.

Patients were usually examined once weekly at first,but with more prolonged observation, the intervalbetween visits was lengthened to 2 to 4 weeks. Thejoints were evaluated at each visit for subjective improve-ment in pain, stiffness, and changes in mobility, and forobjective improvement in tenderness, heat, swelling,range of motion, capsular thickening, and amount ofsynovial fluid present. A composite estimate of thesefindings was recorded as a percentage.The interval between injections was usually determined

by the patient's subjective response, particularly thereturn of significant pain. A degree of improvementgreater than 50 per cent. was the intent in each subject,and a worsening to this level or lower after initial improve-ment was the indication for another injection. Althoughan effort was made to maintain improvement at a satis-factory level (50 per cent. or better), some of the patientsdropped below this figure for a few days before their nextinjection of steroid.The duration of observation varied (Table III).

Approximately half the patients were studied for 1 yearor more, and seven of these for more than 2 years.Other therapy was continued as prescribed before the

study was instituted with the exception of orally-adminis-

TABLE IIIDURATION OF STUDY

Length of Observation Number of Patients

(days)1-100 16

101-200 15201-365 15366-730 33

More than 2 yrs 7

tered steroids; 38 patients were receiving steroids orallyat the onset, and in most instances, an attempt was madeto discontinut. or lower their dose. In a few cases, whenthe beneficial effect from an injection of the intramuscu-larly administered hormone was diminishing and therewas a wait of several days until the next visit, small dosesof steroids were given orally to minimize worsening andto keep the patient more comfortable; 62 patients werereceiving gold salt therapy, and almost all were takingsalicylates simultaneously. In the group of eighteenpatients who received DM as the only injectable steroid,only two were taking steroids orally at the time.

Signs of physiological side-effects and toxicity weresought at each visit. Observations were made for bloodpressure changes, moon facies, ecchymoses, hirsutism,oedema, alterations in body weight, gastrointestinaldisturbances, and other possible reactions. Laboratoryprocedures included blood counts, erythrocyte sedimen-tation rates (Westergren), and urine analyses. These wereperformed on the day of injection, at one week after eachnew steroid administration, and also at varying intervalsduring the study.

ResultsThe average duration of satisfactory improvement

after a single injection of the 100 mg. TACTN,TDAC, DM, TM, and TATBA was approximately20, 16, 18, 16, and 18 days respectively (Table IV).500 mg. FAC resulted in improvement averaging5 2 days per injection. Approximately 70-85 percent. of injections with any compound except FACgave a satisfactory response. A satisfactory res-ponse was defined as greater than 50 per cent.improvement for 7 or more days. TACTN provedthe most beneficial; 87 per cent. of injections werefollowed by a desirable outcome, averaging 20-5days per injection. Table IV also records thelongest periods of improvement from these steroids,extending to 6 months in one instance. Spontaneousremissions have to be considered here.

TABLE IV

RESULTS OF INTRAMUSCULAR STEROIDS IN RHEUMATOID ARTHRITIS

Triamcinolone

Steroid...|Triamcinolone Triamcinolone -PHydrocortisone Ac ActonideSteroid.Acetonide Diacetate Prdnsoono ehl Aeae Actonide Tertiary.Triamciolone riamcoone rtinisoofn-ety Acae Monoenanthate Butylacetate

Dose (mg.).100 100 100 500 100 100

Average Duration ofImprovement (days) 20-5 15*9 18*4 5 *2 16*0 17*9

Satisfactory* ..87% 75% 80% 36% 70% 67%Longest Duration ofImprovement (days) .. 181 75 152 17 >49 160

* Greater than 50 per cent. improvement for 7 or more days.

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INTRAMUSCULAR STEROIDSWhen 50 mg. TACTN was compared to 100 mg.

TACTN in the same individuals, the larger injectionproved to be more satisfactory for degree of im-provement in seven of ten cases and for duration ofbeneficial effect in eight of ten cases, averaging about8 days longer per injection. 140 mg. TACTNcompared with 100 mg. TACTN in six cases resultedin a greater duration of improvement in five patients,averaging about 11 days longer per injection. Thedegree of improvement was approximately the samewith the 100 and 140 mg. doses, except that twopatients felt slightly better after the larger dose.When at least two injections each of the different

steroids were compared in individual patients,TACTN gave the most satisfactory results, beingsuperior to TDAC in 15 of 23, to DM in 13of 22, to TM in five of seven, and to TATBA ineight of ten patients. However, the results were notconsistent, and TDAC proved superior to TACTNin eight patients, DM better than TACTN in ninepatients, and TM and TATBA better than TACTNin two patients each.At times there was a variability in response

between one injection and the next. Thus, it waspossible for a specific steroid to give satisfactoryimprovement after one injection, which was followedby a poor response after the next injection. Thisoccurred with all the steroids studied, and its causewas not apparent. In many instances, there wasno marked deterioration to indicate that any changehad occurred which could have reduced the effective-ness of steroid therapy. However, a third dose ofthe same hormone often had a beneficial resultonce again.The onset of improvement after an intramuscular

steroid injection was usually first noted on awaken-ing the next morning. A few patients experiencedrelief in as little as 3 to 5 hours after an injection,and some not until 48 hours afterwards. Theimprovement was most often at its maximum on theday after injection, but in a few individuals itgradually reached its maximum after several days.

Simultaneous treatment with salicylates and goldsalts had no significant effect on the results. It waspossible to discontinue the oral use of steroids in27 of 38 patients who had been receiving oral steroidsat the start of the study. It was usually easier toreduce the oral dose gradually, particularly if onewere waiting for the total dosage of gold salts toaccumulate to a therapeutic level in the body tissues.If doses of oral steroids were less than the equivalentof 12-5 mg. of prednisolone daily, abrupt dis-continuation at the time of the first intramuscularinjection was frequently possible.

In approximately 25 per cent. of patients, intra-

muscular steroid therapy proved more satisfactorythan oral. Only a few individuals expressedpreference for the oral route. In ten patients acombination of intramuscular and oral steroidsproved more beneficial than either alone.

Side-EffectsThe significant side-effects are shown in Table V.

TABLE V

SIDE-EFFECTS OF INTRAMUSCULAR STEROIDS,86 PATIENTS

Number Number of PatientsSide-Effect of also on

Patients Oral Steroids

Moon facies.30 7Ecchymoses. 31 7Hirsutism. 13 5Diuresis.11 -

Muscle cramps. 8Flushing. 7Epigastric burning.5 1Nausea and/or vomiting .. 4 -

Anorexia . . 1 1Duodenal ulcer .1 1Tiredness and weakness .. 5 -

Euphoria .1.I -Severe pain at site of injection 3 -

Nervousness.2 -

Headache.2 -Increased appetite.3 -

Soft tissue atrophy at site of injection 1 -

Dizziness.3 -Raised blood pressure .. 1 -

Glycosuria.2 -Acne.2 -Menstrual changes.4 -Posterior subcapsular cataracts 3 -Abdomen "hot" and euphoria

shortly after injection .. 1-

It was not possible to indict a specific steroid asthe cause of any particular physiological change ortoxic reaction because the steroids were given inrotation and the cumulative effect had to be con-sidered. The recorded side-effects include datafrom the eighteen patients treated with DM aloneas these findings were similar to the rest. Somepatients were taking oral and intramuscular steroidssimultaneously, so that one could not distinguish thereactions due to the latter alone. Thus, althoughmoon facies, ecchymoses, and hirsutism were themost common physiological side-effects, about30 per cent. of the patients so affected were receivingoral as well as intramuscular steroids.

Moon Facies.-This definitely diminished after severalmonths of intramuscular therapy in five patients whoreceived injections at intervals of at least 3 weeks. A likenumber of cases showed an increase in moon facies andhirsutism, but they received the steroid injections morefrequently.

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ANNALS OF THE RHEUMATIC DISEASESEcchymoses.-These were very common and tended

to recur for many months after the last injection.

Diuresis.-Eleven patients noted this after the injec-tions.Oedema.-If ankle oedema was present, it would, in

many instances, disappear after an injection, only torecur when the beneficial effect from the medication hadwaned.

Muscle Cramps.-These were also not infrequent, butwere generally adequately controlled by quinine orBenadryl* prescribed at bedtime.

Gastrointestinal Complaints.-These were very few andmuch less than those caused by oral steroids in the samepatients. Epigastric burning, nausea, vomiting, andanorexia were noted infrequently. Only one patientdeveloped a duodenal ulcer during treatment with intra-muscular steroids, but he had a previous history of pepticdisease. Three individuals had an increase in appetite.Routine x rays ofthe gastrointestinal tract were not taken.Extreme Tiredness and Weakness.-Occasionally asso-

ciated with nausea and vomiting, this occurred in fivepatients about 10 to 14 days after the steroid injections.These symptoms corresponded with worsening of jointcomplaints and were suggestive of adrenal insufficiencyor of the withdrawal syndrome noted after abruptdiscontinuation of oral steroid therapy. Electrolytedeterminations for sodium, chloride, and potassium intwo of these patients at the time of symptomatology didnot, however, reveal any abnormalities. These symptomswere relieved by a subsequent steroid injection; or, ifnone were given, would persist for 2-4 days and thenusually disappear.

Atrophy ofSoft Tissues.-This developed in one patientover the deltoid injection site in an area measuringapproximately 4 x 4 x 2 cm. This persisted for6 months, but then gradually filled in completely. Therehad been twelve intramuscular injections of the differentsteroids in this region. No abscesses occurred.

Transient Glycosuria.-This appeared in two patients,who had had injections on an average of every 4 weeks;the glycosuria was not present at each visit. No anti-diabetic therapy was necessary.

Posterior Subcapsular Cataracts.-These were dis-covered in three patients who had visual complaints;they had all been on long-term oral steroid therapy beforethe intramuscular injections were given. Under investi-gation at present is a study to evaluate the incidence ofthis complication in our patients.

Osteoporosis.-No patient complained of symptomssuggestive of osteoporosis, but routine x rays ofbone werenot obtained to determine the relative frequency of thisdisturbing physiological effect.

Not all injections of the same hormone resultedin similar reactions in the same individual. Forexample, euphoria, muscle cramps, weakness, and

* Diphenhydramine hydrochloride.

gastrointestinal complaints did not occur con-sistently after similar steroid injections.

DiscussionDespite favourable responses to steroid therapy

in many illnesses, undesirable side-effects accom-panying prolonged administration are still of majorconcern. In an effort to eliminate or temper thesecomplications, newer preparations have been deve-loped, and methods of administration other thanthe usual oral procedure have been tried. Unfor-tunately, all the anti-inflammatory hormones so farmade available still cause many of the same harmfulreactions. Different methods of administrationhave been attempted with partial success, as with theintra-articular injection of steroids and its well-established advantages. However, this latter methodis limited because it results in local improvementonly and does not satisfy the needs of those withmore extensive disease. Recently, Harter, Reddy,and Thorn (1963) described an intermittent oralcorticosteroid dosage regimen with encouragingresults. Their subjects had substantially reducedside-effects, in particular less adrenal suppression.That the intramuscular method is effective is

demonstrated by the satisfactory responses whichfollowed the great majority of injections in thisstudy. TACTN proved to be most desirable. Eighty-seven per cent. of injections with this steroid gave abeneficial effect which persisted for an average ofapproximately 20 5 days per administration. Otherreports (West, 1962; Norcross and Winter, 1961;Hartfall, Walker, and Wright, 1962; Schwartz, 1963)in the literature confirm this impression of theefficacy of intramuscular steroid therapy. West(1962) treated sixteen patients with weekly intra-muscular injections of prednisolone acetate for31 years with favourable responses, the anti-inflammatory effect being about the same as withoral steroids. Norcross and Winter (1961) injectedDM intramuscularly; they felt that it offered certainadvantages over oral steroids in selected patients,but did not recommend it for routine adminis-tration. Hartfall and others (1962) gave pred-nisolone trimethylacetate intramuscularly toseventeen patients and reported improvement innine. Schwartz (1963) found intramuscular steroidsvaluable for long-term treatment, his patients beingimproved for 14 to 21 days after one injection of40 mg. TACTN. In our study, about 25 per cent.of patients responded better to intramuscular thanto oral steroids, and about 10 per cent. seemed to bebetter when oral and intramuscular steroids wereused simultaneously.

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INTRAMUSCULAR STEROIDS

Side-effects.-The known side-effects of oralsteroids were also observed with intramusculartherapy, the frequency and severity of the reactionsdepending to a great extent on the interval betweeninjections. If 4 weeks or more elapsed betweeninjections, such side-effects as moon facies, hirsutism,and acne, for example, were less frequent and lessintense. Since it was possible to obtain satisfactorytherapeutic responses in many patients with suchwidely-spaced injections, this method proved moredesirable for them. Injections given more oftenthan once every 3 weeks were followed by com-plications similar to or more severe than those due tooral steroids. Consequently, the interval betweeninjections should be as long as possible; they shouldbe repeated only when considered essential becauseof significant worsening in the patient's condition,and not given routinely at set intervals.The dose per injection is also very important when

considering side-effects, but as 100 mg. was usedfor the majority of injections in this study, a properevaluation of the relationship of dose to toxicitywas not possible.The various authors who have used the intra-

muscular route have all concluded that gastro-intestinal complications are definitely fewer thanwith oral steroids, and this has also been our experi-ence.

Other Advantages.-Besides the advantagesalready mentioned (i.e. greater anti-inflammatoryeffect in certain patients and less toxicity if theinjections are widely separated), other considerationsare pertinent:

(1) The medication is expensive, but the totalcost may be less than that of oral therapy if theinjections are not too frequent.

(2) Withdrawal symptoms seem to be less markedand can be controlled if they do occur with smalloral doses.

(3) The intramuscular method of administrationis relatively simple, and the regulation of dosage bygradual reduction or addition can be avoided in mostinstances.

Dosage.-To determine the optimum dose, injec-tions of 50 and 140 mg. TACTN were given to somepatients and compared with the 100 mg. dose. The50 mg. dose was significantly less satisfactory, andthe improved response to the 140 mg. dose did notseem to warrant its routine use because of the risk ofgreater toxicity. Doses between 50 and 100 mg.were not evaluated, but the 100 mg. dose proved veryefficacious for most patients in this study.

Prolonged Response.-The reason for the pro-longed response which followed the intramuscularinjections of TACTN, TDAC, DM, TM, andTATBA is not known. A "depot" effect may partlyexplain it, and to test this, five of our patients weregiven DM intramuscularly and tablets of 6-methylprednisolone orally in the same 100 mg. dose, butat different times. Oral therapy gave 2 days'improvement, whereas the intramuscular route gave3 weeks. This type of information supports thelikelihood of a "depot" effect. However, certainunknown factors (such as, the rate of absorptionthrough the gastrointestinal tract of the orallyadministered steroid, the amount absorbed, and theimportance of passage through the portal circulationas the initial pathway for the steroid) require evalua-tion. The development of better methods of assay-ing the blood levels of these steroids should givedefinite answers. The prolonged response may bedue to an initial high blood level of the drug resultingfrom the large dose injected. Higher concentrationsof steroid may thus enter the inflamed synovial cellsand suppress the inflammation more efficiently,particularly if the permeability of these cells is alteredby inflammation. Passage through the systemiccirculation before the portal circulation, thus tem-porarily avoiding the effect of the liver cells on themetabolism of the steroids, may also leave moresteroids available to enter the inflamed synovial cell.However, since the steroid levels may be assumed tohave been high in the blood of the patients whoreceived 100 mg. 6-methyl prednisolone orally, butresponded poorly, the significance of this explanationis doubtful.

SummaryThe intramuscular administration of steroids in

an attempt to combine a good anti-inflammatoryresponse with relatively minor toxicity was tested ina series of 920 injections. The desired anti-inflam-matory effect was obtained in approximately70-85 per cent. of instances with 100 mg. injectionsof TACTN, TDAC, DM, TM, and TATBA, mostfrequently with TACTN. The duration of improve-ment was greatest following the administration ofTACTN (average 20 5 days per injection). A50-mg. dose of TACTN was significantly lesssatisfactory than the 100 mg. dose. The greaterimprovement in a few patients after a 140-mg. doseof TACTN did not seem to warrant the use of thislarge dose routinely because of the greater risk oftoxicity.

Evaluation of toxic side-effects will require moreprolonged observation, but there is evidence that ifinjections are relatively widely spaced (i.e. more than3 weeks apart), the side-effects may be fewer than

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ANNALS OF THE RHEUMATIC DISEASESwith oral steroids. Intramuscular treatment may

be particularly advantageous in limiting gastro-intestinal complications. About 25 per cent. ofthe patients derived more satisfactory relief fromintramuscular steroid therapy than from previousoral steroid therapy.

REFERENCES

Harter, J. G., Reddy, W. J., and Thorn, G. W. (1963).New Engl. J. Med., 269, 591.

Hartfall, S. J., Walker, W. C., and Wright, V. (1962).Acta rheum. scand., 8, 258.

Norcross, B. M., and Winter, J. A. (1961). N.Y. St. J.Med., 61, 552.

Schwartz, S. (1963). Curr. ther. Res., 5, 431.Steinbrocker, O., Traeger, C. H., and Batterman, R. C.

(1949). J. Amer. med. Ass., 140, 659.West, H. F. (1962). Ann. rheum. Dis., 21, 191.Zuckner, J. (1961). Ibid., 20, 274.

Administration intramusculaire de st6roides dansle traitement de l'arthrite rhumatismale

RESUMEOn a etudie l'administration intramusculaire de

steroides par une serie de 920 injections pour trouver unebonne reponse anti-inflammatoire avec un minimumrelatif de toxicite. L'effet anti-inflammatoire desire futobtenu en 75-85 pour cent des cas avec 100 mg. de6-methyl prednisolone d6p6t et avec chacune des quatrepreparations de triamcinolone: acetonide, diacetate,acetonide monoenanthate et acetonide butylacetateterciaire, mais le plus souvent avec l'actonide de triam-cinolone (TACTN). La duree de l'amelioration fut laplus longue apres l'administration de TACTN (20,5 jourspar injection en moyenne). Une dose de 50 mg. deTACTN fut significativement moins satisfaisante que ladose de 100 mg. Le fait que l'amelioration fut plusprononcee chez quelques malades avec une dose de 140

mg. de TACTN ne justifie pas son emploi regulier enraison du risque plus grand de toxicite.

L'evaluation des effets toxiques exige une observationplus longue, mais on sait deja que lorsque l'intervalleentre les injections est assez long (c.-a-d. plus de troissemaines) les effets secondaires sont moins frequentsqu'avec les steroides par voie orale. Le traitementintramusculaire est particulierement avantageux pourlimiter les complications gastro-intestinales. Pres de25 pouI cent des malades derivaient un soulagement plussatisfaisant de la therapie steroide intramusculaire quede la therapie steroide anterieure par la voie orale.

Administraci6n intramuscular de esteroides enel tratamiento de la artritis reumatoide

SUMARIOSe estudi6 la administraci6n intramuscular de estero-

ides en una serie de 920 inyecciones para hallar unabuena respuesta anti-inflamatoria con un minimorelativo de toxicidad. El efecto anti-inflamatoriodeseado fue obtenido en un 75-85 por ciento de los casoscon 100 mg. de 6-metil prednisolona dep6t y con cada delas cuatro preparaciones de triamcinolona: acetonido,diacetato, acetonido monoenantato y acetonido butil-acetato terciario, pero con la mayor frecuencia con elacetonido de triamcinolona (TACTN). La duraci6n dela mejoria fue mayor despues de la administraci6n deTACTN (20,5 dias en promedio por inyecci6n). Unadosis de 50 mg. de TACTN fue significativamente menossatisfactoria que la dosis de 100 mg. La mejoria maspronunciada en algunos enfermos con una dosis de 140mg. de TACTN no justifica su empleo regular en vistadel riezgo de mayor toxicidad.La valoraci6n de los efectos t6xicos necesitaria mas

larga observacion, pero existen datos mostrando que conun intervalo entre las inyecciones suficiente (p.ej.mas detres semanas) los efectos secundarios son menos fre-cuentes que con esteroides por via oral. El tratamientointramuscular es particularmente ventajoso para limitarlas complicaciones gastrointestinales. Cerca de un 25por ciento de los enfermos experimentaron un aliviomAs satisfactorio con la terapia esteroide intramuscularque con la terapia esteroide previa por via oral.

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