A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis. Isotopic indices as a measure of inflammation in rheumatoid arthritis. Indomethacin or prednisolone at night in rheumatoid arthritis? Low dose prednisone therapy in rheumatoid arthritis: a double blind study. Evaluation of digital joint circumference measurements in rheumatoid arthritis. Method for Assessing Therapeutic Potential of Anti-inflammatory Antirheumatic Drugs in Rheumatoid Arthritis Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial. Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group. Reduced loss of hand bone density with prednisolone in early rheumatoid arthritis: results from a randomized placebo-controlled trial. Ibuprofen in rheumatoid arthritis. Clinical study of analgesic and anti-inflammatory activity. Low-Dose Prednisone Induces Rapid Reversible Axial Bone Loss in Patients with Rheumatoid Arthritis Glucocorticoid receptor up-regulation in early rheumatoid arthritis treated with low dose prednisone or placebo. A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial. The clinical effect of glucocorticoids in patients with rheumatoid arthritis may be masked by decreased use of additional therapies. Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. Endocrine control of inflammation: rheumatoid arthritis double-blind, crossover clinical trial. Clinical measurement of the anti-inflammatory effects of salicylates in rheumatoid arthritis. LONG-TERM STUDY OF MANAGEMENT OF RHEUMATOID ARTHRITIS Risk of infectious complications in patients taking glucocorticosteroids. Publication bias: evidence of delayed publication in a cohort study of clinical research projects An assessment of grip strength measurement in rheumatoid arthritis. Low-dose glucocorticoids in early rheumatoid arthritis: discordant effects on bone mineral density and fractures? Low-Dose Prednisone Therapy for Patients with Early Active Rheumatoid Arthritis: Clinical Efficacy, Disease-Modifying Properties, and Side Effects: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Evaluation of a functional index in rheumatoid arthritis. Evaluation of drug efficacy by a preference technic. Evaluation of analgesic action and efficacy of antirheumatic drugs. Study of 10 drugs in 684 patients with rheumatoid arthritis. The effect of low doses of prednisolone compared with placebo on function and on the hypothalamic pituitary adrenal axis in patients with rheumatoid arthritis. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group.
OBJECTIVES To compare budesonide , a locally acting glucocorticoid with minimal systemic exposure , with conventional glucocorticoid treatment and placebo in rheumatoid arthritis . METHODS A double blind , r and omised , controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis , comparing budesonide 3 mg daily , budesonide 9 mg daily , prednisolone 7.5 mg daily , and placebo . Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment . RESULTS There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo ( 28 % for tender and 34 % for swollen joint counts , p<0.05 ) . Prednisolone 7.5 mg gave similar results , while budesonide 3 mg was less effective . ACR20 response criteria were met by 25 % of patients on placebo , 22 % on budesonide 3 mg , 42 % on budesonide 9 mg , and 56 % on prednisolone 7.5 mg . A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks . There was no evidence that budesonide provided a different pattern of symptom control from prednisolone , or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment . Adverse effects attributable to glucocorticoids were equally common in all groups . CONCLUSIONS The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment , are maintained for three months , and are not associated with any rebound in symptoms after stopping treatment Assessment of inflammation in rheumatoid arthritis ( RA ) has been studied in several different ways . Hart and Huskisson ( 1972 ) considered morning stiffness to be a reflection of inflammation with the disadvantage of being subjective . Boardman and Hart ( 1967 ) used proximal interphalangeal joint circumference which is at least objective , but may not be responsive to anti-inflammatory therapy , for example in patients with long-st and ing or ' burnt-out ' disease . Dick , Neufeld , Prentice , Woodburn , Whaley , Nuki , and Buchanan ( 1970 ) found that external count rates over single inflamed joints were greater than those over normal joints . They used technetium 99 ( 99Tc ) , an isotope with a half-life of 6 hours , and showed reduction in counts after treatment with anti-inflammatory drugs . In a previous study , Huskisson , Berry , Browett , and Balme ( 1973 ) showed , no relationship between technetium count over a single joint and any other measurement , arguing that reduction in count rate over a single joint could not be equated with anti-inflammatory effect . These authors also used an index based on counts over both wrists and knees , and in a small study there was a significant correlation with articular index . Though highly protein bound , 99Tc is presumably distributed to some extent in the extravascular extracellular space . Huskisson and others ( 1973 ) showed , by simultaneous counting of a blood sample and of soft tissues over the forearm , that 99Tc tended to remain more within the vascular compartment in patients with rheumatoid arthritis than in normals . Since most authors have suggested that 99Tc measures ' vascularity ' , an isotope which remains entirely within the circulation might be more useful for this purpose . In this study , Indium 113 ( 113In ) , a gamma emitter with a half-life of 99 5 minutes , was used . It is believed that it remains almost entirely within the circulation ( Stern , Goodwin , Scheffel , Wagner , and Kramer , 1967 ) . The 113kIn and 99Tc indices have been compared and their responsiveness to anti-inflammatory therapy assessed Indomethacin , 100 mg orally , was compared with prednisolone , 5 mg , as addititional therapy at night , in a two-week , double-blind , between-patient study in twenty-four in- patients with rheumatoid arthritis . Both therapies proved equally effective , and significantly lessened morning stiffness and increased grip strenght .  Two patients with dyspepsia were discontinued from the indomethacin group . Using indomethacin at night avoided the central nervous system side-effects frequently seen with this compound Prednisone , 5 mg taken each morning , was added to other drugs in 18 patients with rheumatoid arthritis . Sixteen patients were given a placebo  in this double blind study . After 24 weeks , all patients were given the placebo .  Slight functional improvement was noted in the prednisone group during the 24-week period , but deterioration after switching to placebo was sustained for at least 8 weeks . Progression of h and erosions occurred in 1 prednisone-treated patient , and in 4 controls . An asymptomatic vertebral spine compression fracture developed in 2 patients given prednisone ; this was the only toxicity noted possibly due to this therapy . Minimal dose prednisone may be useful as " bridge " therapy between nonsteroidal antiinflammatory therapy and use of disease-modifying drugs Measurement of digital joint circumference by using a plastic spring gauge has been carefully evaluated in rheumatoid patients . There is very small Ultra-observer but large inter-observer variation . A diurnal change in joint size could not be confirmed . Provided that joints affected by soft tissue swelling are used , the measure is a useful Index of the effect of anti-inflammatory drugs . John Webb Centre for Rheumatic Diseases 35 Baird Street Glasgow , G. 40 EH Scotl A 14-day , single-blind trial of prednisone , aspirin , and placebo was carried out in 128 patients suffering from rheumatoid arthritis , using subjective criteria only ( severity of pain daily on a pain chart and assessment of the drug for effectiveness ) . The average treated pain rating , mean patient satisfaction rating , and mean number of days withdrawn from each drug all showed significant differences between prednisone , aspirin , and placebo . Of various pretreatment observations , only the initial pain score and articular index of joint tenderness were significantly related to the average treated pain rating . The trial method is simple and allows many patients to participate without being time consuming for patient or physician . The method seems to have potential in comparing the comparative effectiveness of anti-inflammatory analgesics used in the treatment of patients with rheumatoid arthritis BACKGROUND Evidence for disease modifying activity of low dose corticosteroid treatment in rheumatoid arthritis is contradictory . Studies showing radiological benefit suggest that continued treatment is required to sustain the effect . OBJECTIVE To evaluate the effect of low dose oral prednisolone in early rheumatoid arthritis on disease activity over two years . DESIGN Double blind placebo controlled trial . METHODS Patients with rheumatoid arthritis , duration <3 years ( n = 167 ) , were started on a disease modifying antirheumatic drug ( DMARD ; sulphasalazine )  and allocated by stratified r and omisation to prednisolone 7 mg/day or placebo . Primary outcome measure was radiological damage , assessed by the modified Sharp method . Clinical benefit was a secondary outcome . A proactive approach to identifying and treating corticosteroid adverse events was adopted . Patients who discontinued sulphasalazine were offered an alternative DMARD . RESULTS 90 of 257 patients eligible for the study refused to participate ( more women than men ) . Of those enrolled , 84 % were seropositive for rheumatoid factor , median age 56 years , median disease duration 12 months , female to male ratio 1.8:1 .  Prednisolone was given to 84 patients ; of these 73 % continued prednisolone and 70 % sulphasalazine at 2 years . Of the 83 patients on placebo , 80 % continued placebo and 64 % sulphasalazine at 2 years . There were no significant differences in radiological score or clinical and laboratory measures at 0 and 2 years . CONCLUSIONS Low dose prednisolone conferred no radiological or clinical benefit on patients maintained on a DMARD over two years . Low dose corticosteroids have no role in the routine management of rheumatoid arthritis treated with conventional disease modifying drugs OBJECTIVE Prednisolone reduced the progression of joint destruction over 2 yr in early , active rheumatoid arthritis . The response to discontinuation of prednisolone under double-blind conditions is now reported . METHODS A r and omized , double-blind , placebo-controlled trial of prednisolone 7.5 mg daily in addition to routine medication over 2 yr in 128 patients with early rheumatoid arthritis , using radiological progression ( changes in the Larsen score ) and the development of erosions as primary outcome measures . Study medication was blindly discontinued and follow-up maintained for a further year . Other assessment s included disability , joint inflammation , pain and the acute-phase response . RESULTS Similar results were obtained when all available radiographs were included for each year of assessment ( maximum 114 ) and when only patients with radiographs at all time points were included ( 75 patients ) . In these 75 , the mean progression in the prednisolone group was 0.21 Larsen units in year 1 , 0.04 units in year 2 and 1.01 units in year 3 ( P = 0.587 , 0.913 and 0.039 for change within each year , respectively ) . The equivalent placebo group means were 2.34 , 1.00 and 1.63 Larsen units ( P = 0.001 , 0.111 and 0.012 ; difference between groups : 2.13 , 0.96 and 0.67 units , P = 0.082 , 0.02 and 0.622 ) . The percentage of h and s which had erosions at each time point was : prednisolone group : 27.8 , 29.2 , 34.7 and 39.2 ; placebo group : 28.2 , 48.7 , 59.0 and 66.5 . There was little evidence for a flare in clinical symptoms after discontinuation of prednisolone . CONCLUSION Joint destruction resumed after discontinuation of prednisolone . This corroborates the previously reported therapeutic effect and challenges current concepts of disease pathogenesis BACKGROUND Bone damage in rheumatoid arthritis presents as osteoporosis and joint erosions . Prednisolone has been shown to reduce the rate of h and joint destruction as seen on radiography but has not been shown to reduce the rate of h and bone loss . METHODS In a double-blind study comparing oral prednisolone ( 7.5 mg/d for 2 years ) with placebo ,  h and bone density assessed with digital x-ray radiogrammetry was examined in 95 patients with rheumatoid arthritis with disease duration of less than 2 years . RESULTS The mean loss of h and bone density was less in prednisolone-treated patients compared with placebo-treated patients at the 1-year follow-up ( -0.011 vs -0.022 g/cm(2 ) ) ( P = .005 ) and at the 2-year follow-up ( -0.026 vs -0.039 g/cm(2 ) ) ( P = .03 ) . The mean percentage group difference in loss of h and bone density was 2.8 % ( P = .004 ) at the 1-year follow-up and 3.5 % ( P = .01 ) at the 2-year follow-up . In the first year , C-reactive protein , a marker of inflammation , was strongly correlated with h and bone loss in placebo-treated patients but not in prednisolone-treated patients , suggesting that prednisolone breaks the link between bone loss and inflammation . CONCLUSIONS To our knowledge , this is the first double-blind r and omized study to show that disease-related loss of h and bone density in rheumatoid arthritis can be decelerated by prednisolone . This finding suggests that the deleterious effect of prednisolone on bone may be counteracted by its anti-inflammatory effect Ibuprofen ( 2 - 4'-isobutylphenylpropionic acid ) is one of a series of phenylalkanoic acids which have been found to possess analgesic , anti-inflammatory and antipyretic properties . The first of these to be successful in the treatment of rheumatoid arthritis was Ibufenac ( isobutylphenylacetic acid ) ( Chalmers , 1963 ; Thompson , Stephenson , and Percy , 1964 ; Hart and Boardman , 1965 ) and the most recent of the series is Ibuprofen . Pharmacological studies have shown that the compound is between two to eight times more potent than aspirin ( Adams , Cliffe , Lessel , and Nicholson , 1967 ) . In this paper we report a double-blind cross-over study of the analgesic and anti-inflammatory activity in rheumatoid arthritis of a daily dose of 750 mg . Ibuprofen compared with aspirin 5g./day and prednisolone 15 mg./day ; each drug being administered orally for a period of one week Published data on the effects of low-dose ( 10 mg/d of prednisone ) glucocorticoid agents on bone in patients with rheumatoid arthritis ( RA ) are controversial , and it has been suggested that the favorable effects of glucocorticoid agents on the inflammatory process and on physical activity may outweigh the negative effects of these drugs on bone . Previous , mostly cross-sectional studies have shown contradictory results [ 1 ] . Longitudinal studies have been done in patients who had been receiving glucocorticoid treatment for some time , and no increased rates of bone loss were noted [ 2 , 3 ] . Several explanations may be offered for the discrepancies in the literature . First , nonr and omized studies may be subject to selection bias , because RA itself , and its concomitant decreased mobility , may adversely affect bone mass [ 1 ] . Second , it has been documented that negative influences of glucocorticoid agents may be most pronounced in the first months of therapy [ 4 ] , and studies evaluating bone loss in the chronic phase of treatment may thus underestimate the effects of these drugs on bone . R and omized , controlled studies are necessary to avoid selection bias . We report the results of the first r and omized , placebo-controlled study of the initial effects of low-dose prednisone on bone mineral density in patients with active RA . Methods Patients Patients were selected from a single university outpatient clinic , from April 1988 to April 1991 . All patients with classical or definite RA [ 5 ] who started taking intramuscular gold salts were considered for participation in the trial . The decision to start intramuscular gold therapy was left to the rheumatologists in charge of the patients . Patients were admitted to the study only if they fulfilled at least three of five criteria : five or more joints that were tender or painful during motion ; three or more swollen joints ; an erythrocyte sedimentation rate more than 28 mm/h ; morning stiffness for at least 60 minutes ; and a hemoglobin level less than normal limits . Patients with other diseases or medication , including calcium supplements and postmenopausal hormone replacement therapy , that might affect bone mass , were excluded from the study . Introduction of these medications during the study was not permitted . Premenopausal patients were allowed to continue taking oral contraceptive drugs . Female patients who were postmenopausal for fewer than 3 years , or who had irregular menstrual cycles , were also excluded from the study . All patients were white . Informed consent was obtained from all patients . The study was approved by the local Ethics Committee . Study Design and Medication All patients were treated with intramuscular aurothioglucose ( Auromyose ; 20 % oily suspension , Noury Pharma , Oss , the Netherl and s ) according to a st and ard dosage regimen . All patients started with a  test dose of 10 mg before the trial . They then continued with a dose of 50 mg weekly , for 20 weeks . Modification of this regimen was possible if side effects occurred . Aurothioglucose was discontinued after 20 weeks if it was not effective . If a satisfactory response occurred , the dose was decreased . Patients were monitored for side effects weekly during the first 8 weeks of treatment and once every 2 weeks thereafter . The trial was a double-blind , placebo-controlled study for 20 weeks . Patients were followed for an additional 24 weeks after this period . All patients were r and omly assigned to receive either prednisone or placebo treatment . No stratification or block r and omization was used . All assessment s were done without knowledge of the patients ' treatment status . Prednisone was given in a dose of 10 mg once daily for 12 weeks . Thereafter , the dose was gradually reduced : 7.5 mg/d in weeks 13 and 14 , 5.0 mg/d in weeks 15 and 16 , 2.5 mg/d in weeks 17 and 18 , and no prednisone in weeks 19 and 20 . This result ed in a total dosage after 20 weeks of 1050 mg and a mean daily dose of 7.5 mg . All patients used nonsteroidal anti-inflammatory drugs throughout the study . Assessment s of Rheumatoid Arthritis All clinical assessment s were done by a single observer . Disease activity was measured by a composite index ( disease activity score ) consisting of the erythrocyte sedimentation rate ( millimeters in first hour ) , the Ritchie articular index [ 6 ] , the number of swollen joints , and a visual analogue scale for general health ( range , 0 to 100 mm ; a zero score indicating excellent health ) , which has been constructed and vali date d previously [ 7 , 8 ] . Assessment s were done at baseline ; after 1 , 2 , and 4 weeks ; and thereafter every 4 weeks . Functional capacity was assessed at baseline and after 12 , 20 , and 44 weeks using a health- assessment question naire ( range , 0 to 3 ; a zero score indicating no functional impairment ) [ 9 ] . Assessment s of Bone Mineral Density Bone mineral density ( BMD ) was measured in the lumbar spine by dual-energy , quantitative computed tomography ( effective radiation dose less than 300 microSievert ) with a Somatom DR3 ( Siemens AG , Erlangen , Germany ) . The details of this method have been published previously [ 10 - 12 ] . In short , patients were positioned with the lumbar spine over a calibration phantom , consisting of two stable plastics : a water-equivalent and a bone-equivalent st and ard containing 200 mg of hydroxyapatite per milliliter . Scans were made through the midvertebral level of lumbar vertebrae L2 to L4 , with a slice thickness of 8 mm . Separate regions of interest were automatically defined for the trabecular bone and the anterior cortical bone of the vertebral body . The BMD was then calculated by comparison of the absorption in the region of interest with the absorption in the calibration phantom and was expressed in milligrams of hydroxyapatite per milliliter . Measurements were made at 125 and 85 kilovolt ( kVp ) , and three images were reconstructed from each scan : at 125 kVp , at 85 kVp , and a calcium-equivalent density image after processing by material decomposition techniques .  Dual-energy quantitative computed tomography results were calculated from the calcium density image . For duplicate measurements , the in vivo coefficient of variation ranged between 6.1 % for the trabecular bone and 5.2 % for the cortical bone . To exclude the possibility that new vertebral fractures caused changes in the BMD , lateral spine radiographs were obtained in all patients at baseline and after 44 weeks and were evaluated by an experienced radiologist . Statistical Analysis The change in BMD ( expressed as percentage from baseline ) was chosen as an outcome measurement . This variable followed a normal distribution sufficiently enough to allow the use of t-tests . Paired and unpaired t-tests were used for within- and between-group comparisons , respectively . Ninety-five percent confidence intervals ( 95 % CI ) were also calculated . The possible influence of an imbalance between the two groups with respect to menopausal state was evaluated using analysis of variance . Cumulative disease activity and cumulative functional capacity were defined as areas under the curve for the disease-activity scores and the health- assessment question naire scores , respectively . Differences between placebo and prednisone-treated patients were analyzed using the t-test . All analyses were done using intention-to-treat principles . Results During the recruitment period , 55 patients started aurothioglucose treatment .  Three patients were inadvertently not reported by their treating physician . Nine patients refused to be included in the study for various reasons . One patient did not fulfill the required criteria for active disease . Two patients were excluded because of irregular menstrual cycles , indicating that menopause might be starting . The remaining 40 patients consented to participate in the study . The baseline BMD was similar in both groups . The mean trabecular BMD was 111 mg/mL in the prednisone group and was 111 mg/mL in the placebo group . The mean cortical BMD was 272 mg/mL in the prednisone-treated patients and was 276 mg/mL in the placebo-treated patients . Other baseline characteristics were also similar in the two treatment groups for most variables ( Table 1 ) . There were more postmenopausal women in the  prednisone group , and the duration of postmenopause was longer in the placebo group . During the first period of the study , aurothioglucose was discontinued in nine patients ( four in the  prednisone and five in the placebo  group ) due to side effects . One of the five patients in the placebo group developed an acute , irreversible , and lethal pancytopenia . At the end of the first period of the trial , 16 patients in the prednisone group and 15 in the placebo group still used aurothioglucose . One patient in the prednisone group started methotrexate ( 7.5 mg weekly ) after 18 weeks . Three patients in the prednisone group and four in the placebo group used no second-line antirheumatic treatment at the end of the first trial period . One patient in the placebo group with progressive disease refused further treatment with the trial medication after 4 weeks . She was then treated with prednisone , 10 mg/d , but assessment s were carried out according to the protocol and data from this patient were included in the placebo group for all analyses ( according to intention-to-treat principles ) . Table 1 . Patient Characteristics During the second period of the trial , six patients who were originally assigned to the prednisone group , and who had all discontinued the trial medication according to the protocol , again started to use prednisone . Two patients from the placebo group used prednisone between weeks 20 and 44 . For one patient , who was originally assigned to prednisone therapy , no BMD data were available at week 44 . The composite disease-activity score and its four constituents all showed a marked and rapid improvement of disease activity in the prednisone-treated patients . Cumulative disease activity , as expressed by the area under the curve for the disease-activity scores , OBJECTIVE Low or medium dose prednisone in early rheumatoid arthritis ( RA ) , albeit with significant variation in clinical efficacy , reduces the progression of joint damage . The glucocorticoid receptor ( GR ) number in peripheral mononuclear cells ( P BMC ) might be helpful to predict which patients will respond to low or medium dose prednisone and therefore do not or will not need higher doses . With this in mind we determined in a double blind , placebo controlled study at baseline and yearly the GR number in P BMC . METHODS Eighty-one early RA patients ( disease duration less than one year ) were included . All patients fulfilled the ACR criteria and were disease modifying antirheumatic drugs ( DMARD ) and glucocorticoid-naive . They were r and omly assigned to treatment with 10 mg prednisone daily or placebo . From all patients disease activity ( CRP , number of tender and swollen joints ) , the radiological joint score , bone mineral density , and the GR number in P BMC were measured annually . RESULTS In females the GR number was up-regulated over time in both the prednisone and the placebo group . The same trend was observed in males . No correlations were found between the GR number in the prednisone users at the start of their treatment and changes in radiological scores or bone density after 2 years of treatment . No correlations were found between the GR number at the start and the clinical characteristics after a follow-up of 2 years . CONCLUSION The GR number in the P BMC of early RA patients did not predict which patients would be prednisone responders based on clinical or radiological parameters . However , the up-regulation of the GR number in P BMC in early RA patients towards the GR number of healthy subjects during the first two years of their disease course seems to reflect a recovery or compensatory mechanism as a response to an ongoing inflammatory process . This recovery may be not enough to efficiently control the inflammatory situation OBJECTIVES To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis . METHODS One hundred and two patients with active rheumatoid arthritis were r and omly allocated to treatment with disease modifying anti-inflammatory drug ( DMARD ) alone or DMARD and prednisolone in a one year follow up study . Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient . The mean dose was 6 mg and the mean cumulated dose was 2160 mg . Patients were followed up with disease activity parameters , radiograph of the h and s ( Larsen score ) , and bone mineral density ( BMD ) of the lumbar spine , distal forearm and h and . At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation . RESULTS The results showed that disease activity in the prednisolone treated group was reduced within two weeks . In the DMARD alone group disease activity was gradually reduced over months . At six months there was no difference between the groups as evaluated by an improvement score using a number of ACR criteria . Prednisolone in the present set up was not able to protect significantly against radiological disease progression , although there was a trend towards less progression in Larsen score in the prednisolone group , a matter that was further underlined in an intention to treat analysis . BMD data revealed a significant reduction in spinal BMD in the prednisolone group , whereas prednisolone seemed to have a protective effect against bone loss in the h and and distal forearm . CONCLUSIONS This study does not allow any firm conclusions for or against the treatment of rheumatoid arthritis with prednisolone . The data suggest that the beneficial effects of prednisolone are not as clear cut in established rheumatoid arthritis as in early disease . Furthermore the data indicate that treatment in the chosen relatively low dose does not provide sufficient control of disease . On the other h and the spinal bone loss observed in the prednisolone group does invite considerations about using higher doses The efficacy of oral prednisone as bridge therapy in rheumatoid arthritis ( RA ) was studied . Forty patients starting aurothioglucose were r and omized to receive either prednisone or placebo for 18 weeks . The dose was 10 mg/day in the first 12 weeks , 7.5 mg/day in weeks 13 and 14 , 5 mg/day in weeks 15 and 16 , and 2.5 mg/day in weeks 17 and 18 . Patients were followed for 44 weeks . We found that disease activity was significantly lower in the prednisone group as early as week 1 and continued up to week 12 . Response to prednisone was noticed in 60 % of the patients . After tapering prednisone , a rebound deterioration was noticed at weeks 20 and 24 in 58 % of the responders . No significant differences in X-ray progression were found between the two groups . We concluded that oral prednisone ( 10 mg/day ) significantly reduces short-term disease activity in 60 % of patients with active RA . The rebound deterioration after tapering the dose means that bridge therapy with prednisone using this dose-reduction scheme is not recommended OBJECTIVE Our previous analysis of patients with early active rheumatoid arthritis ( RA ) treated with prednisone or placebo  revealed the following discrepancy : although a significant retardation of joint damage was observed in the prednisone group compared with the placebo group , no differences in clinical variables between the 2 groups were observed , due to greater use of additional therapy in the placebo group . We sought to investigate whether this discrepancy would extend to variables of well-being . METHODS We conducted a double-blind , r and omized , placebo-controlled clinical trial of prednisone ( 10 mg ) in patients with RA ; the duration of the study was 2 years . Following the placebo-controlled trial , a 1-year open-label followup study was conducted in 81 patients with early ( < /=1 year ) active , previously untreated RA . Forty-one patients were allocated to receive oral prednisone , 10 mg/day , and 40 patients were assigned to the placebo group .  Analgesics , nonsteroidal antiinflammatory drugs ( NSAIDs ) , local injections of a glucocorticoid ( only when absolutely necessary ) , and use of physiotherapy were allowed in both groups . After 6 months , sulfasalazine ( 2 gm/day ) could be prescribed as rescue therapy in both groups . At the beginning of the study and every 6 months thereafter , 2 question naires ( the VDF [ Dutch version of the Health Assessment Question naire ] and the IRGL [ Dutch version of the Arthritis Impact Measurement Scales ] ) were administered . A visual analog scale ( VAS ) for morning pain was administered every 3 months . Disease activity and radiologic scores were assessed . RESULTS VDF scores in the 2 groups were not statistically significantly different . No statistically significant differences between groups were observed in almost all parameters of the IRGL . In the prednisone group ( and only at 6 months ) , the VAS scores for morning pain and general well-being showed improvement comparable with the transient improvement in some of the disease activity variables . In the prednisone group , use of NSAIDs , analgesics , local injections of glucocorticoids , and physiotherapy sessions was approximately 50 % that in the placebo group . CONCLUSION Although significant retardation of joint damage in the prednisone group indicates better disease control , no differences between the groups for variables of well-being were found . This discrepancy may be attributed to greater use of additional therapy in the placebo group . In future clinical trials , the use of additional therapies should be taken into account when analyzing the differences in effect between drugs OBJECTIVE To assess the effect of 5 mg/day prednisolone on disease progression in patients with early rheumatoid arthritis ( RA ) receiving st and ardized disease-modifying antirheumatic drug ( DMARD ) therapy .  METHODS Patients with active RA of < 2 years ' duration were r and omly assigned in a double-blinded manner to receive prednisolone or placebo while starting concomitant DMARD therapy ( gold sodium thiomalate or methotrexate ) . H and and foot radiographs were taken at baseline and at 6 , 12 , and 24 months and were evaluated according to the Ratingen score and the total modified Sharp/van der Heijde score ( SHS ) . RESULTS Of 192 included patients , 166 were available for the intent-to-treat analysis ( ITT ) . Seventy-six patients completed the study per protocol ( PP ) . Radiographic progression ( increase in the Ratingen score ) was significantly less with prednisolone than with placebo . The difference in the progression rate between the groups was greatest in the first 6 months . At 24 months in the ITT population , the least squares ( LS ) mean difference was 3.14 ( 95 % confidence interval [ 95 % CI ] 0.94 , 5.34 ) , P = 0.006 . The results were confirmed by the total SHS in the ITT population ( LS mean difference 7.20 [ 95 % CI 0.93 , 13.47 ] , P = 0.022 ) and with the PP population . Clinical and functional outcomes tended to be better and the rate of remissions was higher in the prednisolone group . Side effects were observed more frequently in the prednisolone group than in the control group : weight gain ( 4 versus 0 patients ) , hypertension ( 6 versus 2 patients ) , glaucoma ( 3 versus 0 patients ) , Cushing 's syndrome ( 5 versus 0 patients ) , gastric distress ( 9 versus 4 patients ) , and gastric ulcers ( only with concomitant nonsteroidal antiinflammatory drug therapy ; 3 versus 0 patients ) . No new lumbar fractures were found in either group . CONCLUSION The very low daily dose of 5 mg prednisolone given over 2 years in combination with background DMARD therapy substantially decreased radiographic progression in early RA at low risk A dysfunction in the endocrine control system for inflammation in rheumatoid arthritis serves as the theoretical basis for chronic inflammation in the study design described . Eighteen patients with rheumatoid arthritis , who acted as their own controls , were brought to a minimum symptom state through conventional means , trained , and allowed to control subsequent flares by a patient-initiated , flare-response prednisone regimen . The six-month trial was double-blind with a crossover at midpoint . While continuing stable non-steroidal anti-inflammatory and disease modifying antirheumatic drug therapies , the patients averaged additional 57 % and 75 % reductions from baseline in tender joint count and total pain score , respectively , on the prednisone therapy . The prednisone therapy was differentiated by improvement from that of a placebo by six of the nine parameters evaluated . The adverse events were no more frequent with prednisone than with placebo use . The efficacy of prednisone was increased threefold while reducing consumption by 40 % when compared to the predecessor 5-mg prednisone/day clinical trial November 1967 Urticaria-Moore-Robinson and Warin DICORNAI pigmentosa , and , moreover , on pharmacological grounds it would be unlikely for aspirin , an acid substance , to have such an action , as most recognized histamine liberators are bases . Another possibility would be that aspirin was acting as a hapten , forming an antigen when combined with serum proteins . We have no clear evidence against this , but we would have to assume that at least one in five patients who suffered from chronic urticaria would also have such an allergy to aspirin . That aspirin in some way renders the skin in these patients more sensitive to histamine is suggested by the present report that intradermal histamine weals were larger after aspirin in these patients . In this connexion it is interesting that Juhlin and Rune ( 1962 ) have reported that the threshold to 48/80 , a known histamine liberator , is lowered in acute urticaria . It has been stated in the past that aspirin sensitivity is specific to acetylsalicylic acid and does not extend to related compounds . In the present investigations similar reactions were obtained in most patients from sodium salicylatt and phenyl salicylate , and it would seem likely that it is the salicylic acid radical which is responsible for aspirin reactivity A 10-year study of the management of rheumatoid arthritis was conducted to compare a programme consisting of rest and anti-inflammatory and antirheumatic drugs with one consisting of maintenance of activity , anti-inflammatory and antirheumatic drugs , and systemic steroids where necessary . During this period subjects who did not respond to the treatment allocated went on to a combined treatment programme of rest , anti-inflammatory and antirheumatic drugs , and steroids . Among those who remained in the trial for the 10 years , there was little difference between the two groups in morning stiffness , number of inflamed joints , functional capacity , grip strength , number of American Rheumatism Association criteria present , and whether they remained on their original treatment programme or switched to the combined programme . However , in those who started in the steroid group , the condition of several joints tended to be better clinical ly and radiologically than in those of the other group during and at the end of 10 years of the original treatment programme , at time of transfer to the combined programme , and at the completion of the combined programme . Both groups had as many complications of disease and treatment , and adverse effects attributable to steroids seemed to be restricted to those with severe disease who had not responded to their original programme . A policy of maintaining physical activity plus the judicious use of steroids where required produces , in the long term , results as good as or probably better than a regimen of bed rest and no steroids The association between corticosteroid therapy and subsequent infections was calculated by pooling data from 71 controlled clinical trials . The overall rate of infectious complications was 12.7 % in the 2,111 patients r and omly allocated to systemic corticosteroids  and 8.0 % in the 2,087 controls  ( relative risk [ RR ] , 1.6 ; 95 % confidence interval [ CI ] , 1.3 - 1.9 ; P less than .001 ) . The risk of infection was particularly high in patients with neurologic diseases ( RR , 2.8 ; 95 % CI , 1.9 - 4.3 ; P less than .001 ) and less pronounced in patients with intestinal ( RR , 1.4 ; 95 % CI , 1.1 - 1.7 ; P = .02 ) , hepatic ( RR , 1.4 ; 95 % CI , 0.9 - 2.3 ; P = .25 ) , and renal ( RR greater than 1 ; P = .03 ) diseases . The rate was not increased in patients given a daily dose of less than 10 mg or a cumulative dose of less than 700 mg of prednisone . With increasing doses the rate of occurrence of infectious complications increased in patients given corticosteroids as well as in patients given placebo , a finding suggesting that not only the corticosteroid but also the underlying disease state account for the steroid-associated infectious complications observed in clinical practice Abstract Objectives : To determine the extent to which publication is influenced by study outcome . Design : A cohort of studies su bmi tted to a hospital ethics committee over 10 years were examined retrospectively by review ing the protocol s and by question naire . The primary method of analysis was Cox 's proportional hazards model . Setting : University hospital , Sydney , Australia . Studies : 748 eligible studies su bmi tted to Royal Prince Alfred Hospital Ethics Committee between 1979 and 1988 . Main outcome measures : Time to publication . Results : Response to the question naire was received for 520 ( 70 % ) of the eligible studies . Of the 218 studies analysed with tests of significance , those with positive results ( P<0.05 ) were much more likely to be published than those with negative results ( P0.10 ) ( hazard ratio 2.32 ( 95 % confidence interval 1.47 to 3.66 ) , P=0.0003 ) , with a significantly shorter time to publication ( median 4.8 v 8.0 years ) . This finding was even stronger for the group of 130 clinical trials ( hazard ratio 3.13 ( 1.76 to 5.58 ) , P=0.0001 ) , with median times to publication of 4.7 and 8.0 years respectively . These results were not material ly changed after adjusting for other significant predictors of publication . Studies with indefinite conclusions ( 0.05 P<0.10 ) tended to have an even lower publication rate and longer time to publication than studies with negative results ( hazard ratio 0.39 ( 0.13 to 1.12 ) , P=0.08 ) . For the 103 studies in which outcome was rated qualitatively , there was no clear cut evidence of publication bias , although the number of studies in this group was not large . Conclusions : This study confirms the evidence of publication bias found in other studies and identifies delay in publication as an additional important factor . The study results support the need for prospect i ve registration of trials to avoid publication bias and also support restricting the selection of trials to those started before a common date in undertaking systematic review s. Key messages This retrospective cohort study of clinical research projects confirms the findings of publication bias found in previous studies Delay in the publication of studies with negative results has been identified as an additional important factor in publication bias With the recognised importance of evidence based medicine , these results have important implication s for the selection of studies included in systematic review s Prospect i ve registration of clinical research projects will avoid many of the problems associated with publication bias However , it is also important to restrict inclusion in systematic review s to studies started before a certain date to allow for the delay in completing studies with negative The intra-observer , inter-observer , day-to-day , week-to-week and diurnal variations in grip strength measurement have been studied in patients with rheumatoid arthritis . In addition , the changes in grip strength measurements in a double-blind , cross-over trial of Sodium Salicylate and Prednisolone are reported . An intra-observer error of up to 9 mmHg was found and , in addition , there was also considerable variation in grip strength measurements between different observers . Grip strength is responsive to Sodium Salicylate and Prednisolone therapy but the change in association with the former was minimal — indicating insensitivity of the test . In clinical trials , measurement of grip strength should not only be performed by one observer for each patient but measurements should be made at the same time of day because of its diurnal variation . The inherent errors in the method should be considered when interpreting results of grip strength measurement in such trials OBJECTIVE To investigate the incidence of osteoporotic fractures and effects on bone of low-dose glucocorticoid ( GC ) monotherapy in a group of previously untreated patients with early active RA we performed a double blind , r and omised , placebo-controlled clinical trial . The study duration was 2 years , with an open follow-up during the third year . Patients were r and omly allocated to receive 10 mg prednisone or placebo . METHODS Non-steroidal anti-inflammatory drugs ( NSAIDs ) were allowed in both groups . After 6 months sulphasalazine ( 2 gr daily ) could be prescribed as rescue therapy in both groups . Except for 500 mg calcium supplement daily , no specific preventive measures were taken . This was a normal procedure at the time the study was design ed ( 1989 - 1991 ) . At the start of the study and every 6 months , X-rays of the twelfth thoracic and of all lumbar vertebrae were scored using the Kleerekoper method , and every year biochemical parameters of bone metabolism and bone mineral density ( BMD , expressed in T-scores ) and bone mineral content ( BMC , expressed in g/cm ) were assessed . RESULTS In the prednisone group there was a higher incidence during the study of lumbar vertebral fractures than in the placebo group : 7 vs 4 respectively . This difference did not reach statistical significance however , probably because of the small numbers . One patient of the prednisone group suffered an osteoporotic fracture of the pelvis . In the 2-year study and the subsequent follow-up year , no other peripheral fractures were seen in either group . No significant changes from baseline in BMD and BMC of the hips were seen in either group during the study and the follow-up year . In the lumbar spine , BMD in the prednisone group decreased although not statistically significantly during the whole study . No correlation between changes in serum osteocalcin and BMD was observed . CONCLUSION Low-dose prednisone monotherapy for patients with early active previously untreated RA seems to increase the risk of fractures not only by reducing the BMD but also by changes in bone strength and structure Drug treatment for rheumatoid arthritis usually consists of a combination of a nonsteroidal anti-inflammatory drug ( NSAID ) and a disease-modifying antirheumatic drug ( for example , sulfasalazine , methotrexate , gold salt , or a combination ) . New biological agents , such as tumor necrosis factor- blocking agents and interleukin-1 receptor antagonists , appear promising ( 1 , 2 ) . Glucocorticoids have had a special place in the treatment of rheumatoid arthritis since the publication of the report by Hench and coworkers showing that cortisone dramatically alleviated the symptoms of rheumatoid arthritis by inhibiting inflammation ( 3 ) . This period of enthusiasm in the 1950s was followed by a long period in which glucocorticoids were applied cautiously for rheumatoid arthritis because of their many side effects and the recognition that inhibition of inflammation is not necessarily associated with retardation of joint damage ( 4 ) . Ongoing research on glucocorticoids in rheumatoid arthritis focused on both inflammation and joint damage . Some recent studies showed that glucocorticoids reduced the progression of joint damage when added to therapy with disease-modifying antirheumatic drugs . These findings suggested that glucocorticoids might also have disease-modifying properties . If this could be confirmed , glucocorticoids might be used more often , especially since potential serious adverse effects of glucocorticoid therapy are more easily managed today ( 5 ) . Secondary osteoporosis is inhibited by potent bisphosphonates , and gastrointestinal complications of glucocorticoid therapy , especially in combination with NSAIDs , can be reduced by misoprostol , proton-pump inhibitors , or cyclooxygenase-2 selective NSAIDs . As yet , disease-modifying properties of low-dose glucocorticoids as monotherapy for patients with early rheumatoid arthritis have not been investigated . The aim of our study was to investigate the clinical efficacy , disease-modifying properties , and side effects of low-dose glucocorticoids as monotherapy for previously untreated patients with early active rheumatoid arthritis . Methods Patients From October 1992 through October 1995 , all consecutive out patients at the rheumatology departments of the Deventer and Zutphen Hospitals , the Netherl and s , who were at least 18 years of age and had early previously untreated rheumatoid arthritis ( disease duration < 1 year ) that satisfied classification criteria were invited to participate in the study [ 6 ] . To be included , patients had to have active disease , which was defined as the presence of at least two of the following three criteria : 1 ) early-morning stiffness lasting 30 minutes or longer , 2 ) 28-joint score for tenderness and 28-joint score for swelling of 3 or more , and 3 ) Westergren erythrocyte sedimentation rate of 28 mm or higher after 1 hour ( 7 , 8) . Exclusion criteria were contraindications to prednisone  or NSAIDs  , active gastrointestinal problems , serious complicating diseases , severe hypertension , hemorrhagic diathesis , treatment with cytotoxic or immunosuppressive drugs , alcohol or drug abuse , and psychiatric or mental problems . Informed consent was obtained from all patients before participation . Of the 118 eligible patients , 37 declined to participate ( Figure 1 ) . Figure 1 . Trial profile . Intervention Pharmacy personnel at Deventer Hospital used a computer-generated r and omization procedure to r and omly assign the 81 participating patients , in blocks of 10 , to one of two treatment groups . One group received two tablets of prednisone , 5 mg , once daily at breakfast , and one group received placebo . The pharmacology department at Deventer Hospital prepared and labeled the prednisone and placebo tablets , which were identical in shape and color , and distributed them to patients in unlabeled boxes . Only the pharmacist could access the allocation table . Both groups of patients received 500 mg of elementary calcium in the evening . The code of r and omization was broken after 2 years of treatment , and the prednisone dosage was tapered . Surplus tablets of the study medication were counted at every visit , and adherence was satisfactory ( 96 % ) . Use of NSAIDs  was not regulated . Local glucocorticoid injections were permitted only when absolutely necessary . Physical therapy and additional use of paracetamol were allowed . After 6 months , sulfasalazine ( 2 g/d ) could be prescribed as rescue medication . The decision to add sulfasalazine was made on clinical grounds ( activity of rheumatoid arthritis ) . Design and Setting The ethics committees of the University Medical Center Utrecht and the Deventer and Zutphen Hospitals approved the trial . The study was considered ethically acceptable when it was design ed ( 19891991 ) ; later , however , it became clear that irreversible joint damage is an early feature of rheumatoid arthritis . With our present knowledge , it would probably be considered unethical to compare the effects of prednisone and placebo in patients who did not receive a disease-modifying antirheumatic drug for at least 6 months . In our study , sulfasalazine could be prescribed as rescue medication only after 6 months to avoid obscuring the effects of prednisone monotherapy . Measurements All clinical outcome measurements , except those for disability and radiologic outcomes , were performed at baseline and every 3 months . Disability , which was assessed with the Health Assessment Question naire , and radiologic outcomes were measured every 6 months . Early-morning stiffness was recorded in minutes ( maximum , 720 minutes ) . Morning pain and general well-being were assessed on a horizontal visual analogue scale ranging from 0 to 100 mm , with 0 representing the best score ( no problems ) and 100 representing the worst score . Swelling and tenderness were assessed with the 28-joint score ( 7 , 8) . Grip strength was measured in kPa with a vigorimeter ( range , 0 to 200 kPa ) ; the mean of three measurements was calculated for each h and . Disability was assessed with a vali date d Dutch version of the Health Assessment Question naire ( Vragenlijst Dagelijks Functioneren ) ( 9 ) , which had a range of 0 to 3 ( 0 represented the best score [ no problems ] , and 3 represented the worst score ) . Serum C-reactive protein level was measured in mg/L. To investigate the possible sparing effect of the trial medication , we recorded the use of NSAIDs and analgesics , the frequency of intra-articular corticosteroid injections , and the use of physiotherapy . The patients recorded the use of NSAIDs , analgesics  , and physical therapy in st and ardized patient diaries . To calculate the use of NSAIDs and to compare different NSAIDs , we arbitrarily chose naproxen as a reference . One thous and mg of naproxen was defined as 1 unit and was considered to be approximately equivalent to 600 mg of azapropazone , 100 mg of diclofenac , 200 mg of flurbiprofen , 1600 mg of ibuprofen , 100 mg of indomethacin , 200 mg of ketoprofen , 15 mg of meloxicam , 1000 mg of nabumetone , 20 mg of piroxicam , and 600 mg of tiaprofenic acid . Every 3 months , the first author recorded use of intra-articular corticosteroid injections . Radiologic outcome measures were erosions , joint space narrowing , and the total score for both ( range , 0 to 448 ) . The total score is the sum of the erosions and narrowing scores in 44 joints in the h and s and feet , assessed on plain radiography and scored with the van der Heijde modification of the Sharp method ( 10 , 11 ) . Radiologic outcome measures also included the number of patients with erosive disease in each group and the number of radiologically affected joints per patient . Radiographs were taken at entry and every 6 months . An assistant prepared the radiographs to be read , and all identifying patient data on the radiographs were concealed from the readers . The readers had no knowledge of patient identity when they scored the radiographs . Radiographs were read in r and om patient order and were scored for each patient in temporal order . Scoring in temporal order clearly has advantages , as a comparative study has shown ( 11 ) . However , with this method , scores can either be stable or increase ; a decrease ( indicating improvement ) is not possible . The first author and an independent radiologist viewed all available radiographs  at one center . When the readers ' total scores for individual cases differed by 25 % or more , agreement was reached through discussion . Joint damage was defined as a score that exceeded 0 . To correct for possible differences between the two treatment groups in the number of patients who developed little or no joint damage , we also analyzed data only from patients who developed joint damage . Furthermore , radiologic damage was also analyzed with a cutoff point of 4 modified Sharp units . A score of 0 to 3 was interpreted as no damage , and scores of 4 or greater were interpreted as joint damage . This cutoff point seems to reflect clinical ly relevant change ( 12 ) and was also used in our study to define erosive rheumatoid arthritis . At the start of the study and every 3 months for 2 years , st and ardized lists were used to document adverse effects . We noted the occurrence of infections and the use of antibiotics ; the latter was checked at the patient 's pharmacy . For hypertension , the first author used a single device to measure blood pressure in mm Hg . For steroid diabetes , serum glucose level was measured in mmol/L. Hyperglycemia was defined according to the World Health Organization st and ard : postpr and ial , a glucose level of at least 11.0 mmol/L ( 198 mg/dL ) , and fasting , at least 6.6 mmol/L ( 119 mg/dL ) . Urinary glucose level was measured by using a semiquantitative method ( dipstick ) . A value less than 2.7 mmol/L ( 49 mg/dL ) was considered negative , a value of 2.7 to 5.5 mmol/L ( 50 to 99 mg/dL ) was considered a trace , a value of 5.6 to 16.6 mmol/L ( 100 to 299 mg/dL ) was considered 1 + , a value of 16.7 to 54.9 mmol/L ( 300 to 989 mg/dL ) was considered 2 + , and a value of 55 mmol/L or greater ( 990 mg/dL ) was considered 3 + . To assess weight gain , An index of functional impairment is described for use in the assessment of rheumatoid arthritis . The index consists of 17 questions and is simple to perform and not time-consuming . The index has a high degree of intra- and inter-observer reproducibility , and can be performed satisfactorily by paramedical and nonmedical personnel , and by the patient himself . The index does not show change in short-term clinical trials of antiinflammatory drugs , but does change with significant improvement in the patient 's functional ability , following , for example , major reconstructive joint surgery . Dr Peter Lee Centre for Rheumatic Diseases 35 Baird Street GlaSgow G4DEH Scotl INCREASED awareness of the importance of properly controlled drug evaluations has brought with it a need for the development of experimental technics that can provide essential information about dr ... A single-blind non-crossover method for assessing the potential effectiveness of  antirheumatic drugs  has been described . The method employs entirely subjective indices and incorporates a daily pain chart for measuring the pain response over the duration of the trial . In addition , the mean number of days withdrawn and patients ' satisfaction rating are measured . The statistical method can correct for initial imbalances between groups and allows for the valid comparison of drugs from separate trials . Ten antirheumatic medications  were evaluated using this technique in 684 patients with rheumatoid arthritis , and the results are in agreement with those of previous studies using st and ard clinical methods . The new method is simple , rapid in performance , economical in terms of cost and time , and has been shown to be sensitive and reproducible . The results indicate that there are no significant differences in efficacy between the currently available non-steroidal , anti-inflammatory analgesic drugs , in the treatment of rheumatoid arthritis A double-blind trial of prednisolone in patients with rheumatoid arthritis using doses of zero , 3 mg and 5 mg is reported . Patients on a dose of 3 mg derived little sustained benefit but subjects on the higher dose showed some improvement which did not last more than two years . Mild suppression of the hypothalamo-pituitary-adrenal axis occurred in both steroid-treated groups BACKGROUND Oral glucocorticoids are widely used to treat patients with rheumatoid arthritis , but their effect on joint destruction , as assessed radiologically , is uncertain . METHODS We conducted a r and omized , double-blind trial comparing oral prednisolone ( 7.5 mg daily for two years ) with placebo in 128 adults with active rheumatoid arthritis of less than two years ' duration . Except for systemic corticosteroids , other treatments could be prescribed . The primary outcome variables were the progression of damage as seen on radiographs of the h and after one and two years , as measured by the Larsen index , and the appearance of erosions in h and s that had no erosions at base line . The radiographs were viewed jointly by a radiologist and a rheumatologist who were unaware of the treatment assignment and the time point at which the films were obtained . RESULTS The statistical analysis of radiologically detected changes was based on 106 patients for whom there were films obtained at base line and two years later . After two years , the Larsen scores increased by a mean of 0.72 unit in the prednisolone group , indicating very little change , and by 5.37 units in the placebo group , indicating substantial joint destruction ( P = 0.004 ) . Of the 212 h and s of these patients , 147 ( 69.3 percent ) had no erosions at the start of the study . At two years , 15 of the 68 such h and s in the prednisolone group ( 22.1 percent ) and 36 of the 79 such h and s in the placebo group ( 45.6 percent ) had acquired erosions ( difference , 23.5 percentage points ; 95 percent confidence interval , 5.9 to 40.7 ; P = 0.007 ) . The patients in the prednisolone group had greater reductions than the patients in the placebo group in scores on an articular index and for pain and disability at 3 months ; for pain at 6 months ; and for disability at 6 , 12 , and 15 months ( all P < 0.05 ) . There was no difference between groups in st and ardized scores for the acute-phase response . The adverse events were typical of those encountered with antirheumatoid drugs . CONCLUSIONS In patients with early , active rheumatoid arthritis , prednisolone ( 7.5 mg daily ) given for two years in addition to other treatments substantially reduced the rate of radiologically detected progression of disease
BACKGROUND The effect of low dose corticosteroids , equivalent to 15 mg prednisolone daily or less , in patients with rheumatoid arthritis has been question ed .
We performed a systematic review of trials which compared corticosteroids with placebo or non-steroidal , anti-inflammatory drugs .
OBJECTIVES To determine whether short-term ( i.e. as recorded within the first month of therapy ) , oral low-dose corticosteroids ( corresponding to a maximum of 15 mg prednisolone daily ) is superior to placebo and non-steroidal , anti-inflammatory drugs in patients with rheumatoid arthritis .