Abstract
Background
Low dose corticosteroid use in RA is currently widespread with up to 80% of patients using prednisone or similar corticosteroid preparations in many arthritis practices, but the value of corticosteroids for the treatment of RA has been debated by several authors.
Objectives
To perform a systematic review of low‐dose corticosteroid efficacy in the moderate term for the treatment of rheumatoid arthritis (RA).
Search methods
We searched MEDLINE from 1966 to 1998, using the keywords "corticosteroids" and "rheumatoid arthritis". We also handsearched all issues of Arthritis and Rheumatism and the Scandinavian Journal of Rheumatology from their dates of first publication to 1994 and examined all Arthritis and Rheumatism abstracts over the 15 year period preceding 1994. References of all identified studies were searched for relevant trials. Authors of unpublished manuscripts were contacted.
Selection criteria
We required that trials be randomized or cross‐over and report at least one of the outcome measures of interest. We also required that trials be of at least three months duration and use prednisone (or a comparable corticosteroid preparation) at a mean dosage of less than or equal to 15 mg/day, compared to placebo or active drug controls.
Data collection and analysis
Data was abstracted by two independent reviewers (LC, KS) using a standard form. We reported results for all available outcomes recommended by the Outcome Measures for Rheumatology Trials (OMERACT) group.
Main results
Very few studies directly assessed the effectiveness of corticosteroids for RA treatment and many were of poor methodologic quality. Only seven of 34 studies identified by our search met criteria for inclusion. Our results indicated that corticosteroids were significantly more effective than placebo controls for four of six outcomes assessed [standardized mean difference for tender joints = ‐0.37 (95%CI: ‐0.59, ‐0.14), swollen joints = ‐0.41 (‐0.67, ‐0.16), pain = ‐0.43 (‐0.74, ‐0.12), and functional status = ‐0.57 (‐0.92, ‐0.22)]. The results for grip strength and ESR were not significant [GS = +0.30 (‐0.19, +0.80), weighted mean difference (WMD) for ESR = ‐7.03 (‐18.06, +4.01)]. The single trial that compared prednisone to aspirin indicated no statistically significant difference between these groups for joint tenderness (0.10 (‐0.35, +0.55) and for ESR [0.00 (‐11.09, +11.09]. Overall, the four outcomes assessed in the single trial that compared prednisone to chloroquine suggested that there was no statistically significant differenece in the effectiveness of these two agents [SMD for joint tenderness = +0.23 (‐0.30, +0.75), swollen joints = +0.43 (‐0.11, +0.96), functional status = ‐0.27 (‐0.80, +0.26), and WMD for ESR = ‐16.00 (‐30.58, ‐1.42)].
Authors' conclusions
Based on the limited data available, moderate‐term prednisone treatment of RA appears to be superior to placebo and comparable to treatment with aspirin or chloroquine in improving several common rheumatoid arthritis disease activity measures.
Plain language summary
The effectiveness of low‐dose corticosteroids in the treatment of rheumatoid arthritis disease activity over the moderate term
Low dose corticosteroid use in RA is currently widespread with up to 80% of patients using prednisone or similar corticosteroid preparations in many arthritis practices, but the value of corticosteroids for the treatment of RA has been debated by several authors.
We included studies that used prednisone (or a comparable corticosteroid preparation) at a mean dose of less than or equal to 15 mg per day. We included studies that utilized either placebo controls or active controls (i.e. comparative studies).
Very few studies directly assessed the effectiveness of corticosteroids for RA treatment and many were of poor methodologic quality. Only seven of 34 studies identified by our search met criteria for inclusion. Our results indicated that corticosteroids were significantly more effective than placebo controls for four of six outcomes assessed [standardized mean difference for tender joints = ‐0.37 (95%CI: ‐0.59, ‐0.14), swollen joints = ‐0.41 (‐0.67, ‐0.16), pain = ‐0.43 (‐0.74, ‐0.12), and functional status = ‐0.57 (‐0.92, ‐0.22)]. The results for grip strength and ESR were not significant [GS = +0.30 (‐0.19, +0.80), weighted mean difference (WMD) for ESR = ‐7.03 (‐18.06, +4.01)]. The single trial that compared prednisone to aspirin indicated no statistically significant difference between these groups for joint tenderness (0.10 (‐0.35, +0.55) and for ESR [0.00 (‐11.09, +11.09]. Overall, the four outcomes assessed in the single trial that compared prednisone to chloroquine suggested that there was no statistically significant differenece in the effectiveness of these two agents [SMD for joint tenderness = +0.23 (‐0.30, +0.75), swollen joints = +0.43 (‐0.11, +0.96), functional status = ‐0.27 (‐0.80, +0.26), and WMD for ESR = ‐16.00 (‐30.58, ‐1.42)].
Background
Few areas of arthritis care management generate as much emotional controversy as the use of low dose corticosteroids for the treatment of rheumatoid arthritis (RA). Low dose corticosteroid use in RA is currently widespread with up to 80% of patients using prednisone or similar corticosteroid preparations in many arthritis practices (Pincus 1992, Pincus 1995, Saag 1996). Despite a relative paucity of published data, several authors have debated the value of corticosteroids for the treatment of RA (Weiss 1989, Caldwell 1991, Ramos‐Remus 1992, Weisman 1993). Weiss advocated a disease modifying role for corticosteroids in RA and Kirwan's randomized, double‐blind controlled trial supports this view (Weiss 1989, Kirwan 1995). Caldwell and Furst proposed that corticosteroids should be used cautiously as a "bridge" to the safer, more effective slow‐acting anti‐rheumatic drugs (Caldwell 1991). Weisman suggested that low dose corticosteroids provide near complete disease activity control in people with a good prognosis, and that they can assist with symptomatic management of patients with seropositive, aggressive disease (Weisman 1993). In contrast, Ramos‐Remus, McDougall, Russell, and colleagues have emphasized corticosteroid toxicity and the natural preservation of functional status that may occur in patients not treated with prednisone (Ramos‐Remus 1992, McDougall 1994).
Despite these qualitative reviews, there has been no quantitative analysis of the literature evaluating the effectiveness of moderate‐term low dose corticosteroids for control of RA disease activity. Meta‐analysis (MA) provides an appropriate statistical framework for quantitatively combining the results of several studies on a similar topic (Naylor 1989, Mann 1990, Nettleman 1992). MA has previously been used to evaluate the effectiveness of second‐line therapies and short‐term low dose prednisolone for the treatment of RA (Felson 1990, Felson 1992, Gøtzsche 1992, Gøtzsche 1998).
Objectives
The aims of our investigation were to perform a systematic qualitative review of studies evaluating low‐dose corticosteroid efficacy in rheumatoid arthritis. We sought to quantitatively combine results from similar studies using meta‐analysis to determine summary measures of corticosteroid efficacy.
Based on clinical perceptions, we hypothesized that low‐dose corticosteroids would prove to be significantly better than placebo and at least equivalent to active controls in improving rheumatoid arthritis disease activity over the moderate term.
Methods
Criteria for considering studies for this review
Types of studies
Criteria for inclusion were based on recommendations of the conference on Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT 1993). We accepted only studies that were randomized controlled or cross‐over trials lasting 3 months or longer.
Types of participants
Patients with a diagnosis of active rheumatoid arthritis.
Types of interventions
We included studies that used prednisone (or a comparable corticosteroid preparation) at a mean dose of less than or equal to 15 mg per day. We included studies that utilized either placebo controls or active controls (i.e. comparative studies).
Types of outcome measures
We required studies to report at least one of the following outcome measures in a quantitative fashion: joint tenderness (JT), joint swelling (JS), grip strength (GS), or erythrocyte sedimentation rate (ESR).
We reported the results of all available outcomes suggested by OMERACT, including: JT, JS, ESR, pain, functional status (FS), patient global assessment, and physician global assessment. We also report grip strength (GS). We did not consider radiographic outcomes in this review since we were evaluating treatment duration substantially shorter than the one year period currently recommended for evaluation of radiographic change in RA.
Search methods for identification of studies
Using "corticosteroids" and "rheumatoid arthritis" as subject headings we performed a computerized literature search of all English language clinical studies from MEDLINE inception in 1966 through to May 1998. The Cochrane Controlled Trials Register will be searched for the next update. The search strategy is in Appendix 1.
We also hand‐searched all issues of Arthritis and Rheumatism as well as the Scandinavian Journal of Rheumatology from their dates of first publication to 1994. To ensure completeness, two independent reviewers examined the reference lists of all identified studies. Furthermore, we examined all Arthritis and Rheumatism abstracts over the period 1980 to 1994 in order to identify preliminary studies that had not been published. The authors of all unpublished manuscripts were contacted.
Data collection and analysis
Once study selection was complete, data on outcome measures was abstracted from the studies at the baseline time point and at the time point closest to six months of follow‐up for both the corticosteroid and the control arms. Data was abstracted by two independent reviewers (LC, KS) using a standard form. During data abstraction, any ambiguities were resolved by consensus of the reviewers, or in several cases by contacting the authors of a given report. We also abstracted data for other variables that might affect outcomes including: patient age, sex, duration of disease, severity of disease (indicated by baseline joint counts and rheumatoid factor seropositivity), and the source of funding for each study.
We conducted a standard meta‐analysis using methods for continuous data developed by Hedges and Olkin (Hedges 82) and described recently by Petitti (Petitti 94). A fixed effects model was used unless the test for homogeneity indicated significant heterogeneity among the studies. The homogeneity of the trials for each pooled analysis was estimated using a chi‐square test. In case of significant heterogeneity, a random effects model was used.
When the scale of a particular outcome varied among the studies, we calculated a standardized mean difference for that outcome. Specifically, we calculated the standardized mean difference in the endpoint outcomes between the corticosteroid and control arms. When there was consistency across studies in the outcome scale used, we calculated the weighted mean difference between the endpoint treatment and control arms. Baseline standard deviations for each treatment arm were used in these calculations using RevMan 3.1. Negative values indicate a benefit of corticosteroids over the control arm.
Results
Description of studies
Although we identified thirty‐four studies of interest for the meta‐analysis, only seven studies met criteria for inclusion (Harris 1983, Million 1984, Van Schaardenburg 95, Van Gestel 1995, Stenberg 1992, Empire 1995, Kirwan 1995). Five were placebo‐controlled (Harris 1983, Million 1984, Van Gestel 1995, Stenberg 1992, Kirwan 1995) and the other two were active‐controlled studies comparing prednisone to another agent, which included chloroquine (Van Schaardebburg 95) and aspirin (Empire 55). The seven studies were published between 1955‐1995. Characteristics of the included studies are shown in the table of Characteristics of Included Studies.
Although the study by Million et al. (Million 1984) reported many outcomes, standard deviations were not provided for most outcomes and pain was available only at 10 years. The study by Kirwan 1995 reported an articular index derived from both joint pain and swelling scores, weighted by the size of the joint. We therefore used this information for both the JT and JS outcome calculations.
Of the studies selected, all enrolled only adults ( > 18 years old), and in six of the seven selected studies at least 90% of subjects were documented to satisfy either the 1958 or 1987 ACR (American College of Rheumatology, formerly American Rheumatism Association) criteria for rheumatoid arthritis. The seventh study was conducted before ACR criteria were in use but the authors indicated that all subjects with arthritis diagnoses other than RA were excluded (Empire 1995). In all but two studies, background use of second‐line agents and/or nonsteroidal anti‐inflammatory agents was allowed. In total, approximately 35 to 45% of subjects in both the corticosteroid and control treatment arms were receiving second‐line agents concurrently. Joint tenderness, joint swelling, grip strength, and ESR were reported most commonly. Particularly deficient, and used only in recent studies, were measures of patient functional assessment using instruments such as the Health Assessment Questionnaire (Fries 1982) or the Arthritis Impact Measurement Scale (Meenan 1982). Ritchie articular index or other quantitative evaluations of joint scores (when reported) were equated with tender joint count (Ritchie 1968, Eberl 1976).
The excluded studies and reasons for exclusion are summarized in the table of excluded studies. Many studies had more than one reason for exclusion. Of the other twenty‐seven studies excluded from the meta‐analysis, twelve did not randomize subjects, three used an average corticosteroid dose above 15 mg per day and seven were of less than three months duration. Two studies used an alternative corticosteroid preparation (deflazacort) as the control arm, and five studies were continuations of earlier reports already included. Of note, from the multiple publications of the Empire Rheumatism Council and the Joint Commission of the Medical Research Council and Nuffield Foundation, we included only one study comparing cortisone with aspirin (Empire 1995).
Risk of bias in included studies
All included studies were formally evaluated for quality using Jadad's scale, which ranges from ‐2 to +5 (Jadad 1996). Six of the seven included studies were also formally assessed using a method developed by Chalmers 1981. This technique assigns a maximum of 100 points to each study depending on the quality of its design. Chalmer's method weights the degree of blinding most heavily, but it also considers other characteristics including the choice of analytic techniques and the control of bias.
Of note and reflected in the quality ratings, only 4 of the 7 studies used a double blind design (Harris 1983, Stenberg 1992, Van Gestel 1995, Kirwan 1995).
Effects of interventions
The included studies involved 253 patients randomized to corticosteroids, 177 to placebo, 50 to ASA and 28 to chloroquine.
The results of our pooled analysis comparing corticosteroids to placebo controls indicated that corticosteroids were significantly more effective than placebo for four of the six outcomes available. The standardized (or weighted) mean differences and 95% confidence intervals for the six outcomes were: JT = ‐0.37 (95%CI: ‐0.59, ‐0.14), JS = ‐0.41 (‐0.67, ‐0.16), pain = ‐0.43 (‐0.74, ‐0.12), FS = ‐0.57 (‐0.92, ‐0.22), GS = +0.30 (‐0.19, +0.80), and ESR (WMD) = ‐7.03 (‐18.06, +4.01).
Only a single trial compared corticosteroids (prednisone) to aspirin (Empire 1995), and only two outcomes were available for this comparison. This comparison indicated no statistically significant difference between these groups for the two outcomes assessed [SMD for JT = +0.10 (‐0.35, +0.55), WMD for ESR = 0.00 (‐11.09, +11.09)].
Four outcomes were available for the single trial that compared prednisone to chloroquine treatment (Van Schaardenburg 95). The results of this study suggested that the effectiveness of these two agents is similar. Specifically, the SMD (or WMD) for the four outcomes were: JT = +0.23 (‐0.30, +0.75), JS = +0.43 (‐0.11, +0.96), FS = ‐0.27 (‐0.80, +0.26), and ESR (WMD) = ‐16.00 (‐30.58, ‐1.42).
All results reported were derived from fixed effects models because we did not find evidence of significant study heterogeneity for any of the comparisons.
Discussion
Our findings highlight the limited data available which directly assess the moderate‐term effectiveness of low‐dose corticosteroids for RA. It was surprising to us that in an area as controversial as this one, published information is so sparse. Furthermore, the existing studies are of generally poor quality reflecting weaknesses in study design. The results of our pooled analyses indicate that corticosteroids appear to be more effective than placebo and comparable to active controls in improving most conventional outcome measures.
Our analysis was not intended to address the relative toxicity of corticosteroids; toxicity concerns have been previously investigated in observational studies by us and others (Michel 1991, Saag 1994, Wolfe 1995). However, putative corticosteroid toxicity was not inconsequential in the studies included in our analysis. For example, in Million and colleagues' study two deaths and six vertebral fractures were potentially attributable to corticosteroids (Million 1984). In comparison, however, second‐line agents used to treat RA are also associated with serious side‐effects (Felson 1992, Fries 1993) and this may limit their long‐term usefulness (Iannuzzi 1983, Kushner 1989). Given the drawbacks of the currently available second‐line agents, as well as data showing that corticosteroids are the RA therapy least likely to be discontinued by a rheumatologist over a five year period (Pincus 1992), we undertook this critical assessment of the RA corticosteroid effectiveness literature.
The subjects included in our meta‐analysis are representative of the general RA population likely to be prescribed corticosteroids (Byron 1986). However, the generalizability of our results to older, rheumatoid arthritis patients and to patients with a longer duration of disease may be limited due to the relatively younger age distribution and shorter disease duration of our subjects. Although one of our studies included only subjects with elderly onset rheumatoid arthritis (Van Schaardenburg 95), this study was too small to allow us to determine whether the effectiveness of corticosteroids for RA treatment is systematically different among older RA patients.
Meta‐analysis is not a substitute for large, well designed controlled trials (Borzak 1995). However, it provides a formal quantitative synthesis of the available data (Dickersin 1992). There are general limitations of meta‐analysis (particularly those describing arthritis therapies) including methodologic ambiguities in dealing with continuous data and the potential for publication bias (Chalmers 1987). In addition to these general meta‐analysis limitations, our corticosteroid meta‐analysis was further limited by the small number of studies satisfying inclusion criteria. Indeed, the small number of included studies limits our ability to perform sensitivity analyses among subgroups of the studies.
Background therapy, which included second line drugs in many studies, also may confound interpretation of corticosteroid's independent effect. However, subject randomization and a generally equivalent use of second‐line agents in both the corticosteroid and the non‐corticosteroid treatment arms largely eliminates these concerns.
Data beyond one year were not available in sufficient studies to perform a longer‐term meta‐analysis and determine whether improvements demonstrated over shorter periods are sustained beyond 6‐12 months. In this meta‐analysis, we focused on disease activity outcome measures routinely included in arthritis clinical trials (Felson 1990). Although these measures of disease activity are not a substitute for long‐term evaluation of disease progression (most often assessed by radiographic changes) disease activity measures have a strong association with long‐term disease outcomes (Hassell 1993). As particularly evident in the report by Million et al, and in the open‐label study of Bernsten and others (not included in the meta‐analysis), improvements in disease activity parameters are strongly correlated with patient satisfaction and with better functional ability (Million 1984, Bernsten 61). In a condition like rheumatoid arthritis with such profound socioeconomic consequences (Yelin 1995), even moderate term improvement in function may be a worthwhile objective from both a patient and a societal perspective.
Authors' conclusions
Implications for practice.
Although our findings are based on very few controlled studies, they generally uphold the widely held belief that corticosteroids, when administered for periods of approximately 6 months, are effective for the treatment of RA.
Implications for research.
Further investigation is needed to carefully weigh the relative effectiveness of corticosteroids by their known toxicity, and to assess the effectiveness of longer corticosteroid treatment periods.
What's new
| Date | Event | Description |
|---|---|---|
| 5 November 2008 | Amended | Converted to new review format. CMSG ID: C054‐R |
Acknowledgements
The authors gratefully acknowledge the assistance of Drs. Mary Nettleman, Ms. Sheela Kolluri and Jessie McGowan.
Appendices
Appendix 1. MEDLINE search strategy
001 exp arthritis, rheumatoid/ 002 (rheumatoid adj arthrit$).tw. 003 ((caplan's or felty's or sjogren's) adj syndrome).tw. 004 ankylosing spondylitis.tw. 005 still's disease.tw. 006 or/1‐5 007 exp adrenal cortex hormones/ 008 adrenal cortex hormones.rn,tw. 009 prednisone/ 010 prednisone.tw,rn. 011 corticosteroid$.tw. 012 glucocorticoids.rn,tw. 013 corticosterone.tw,rn. 014 hydrocortisone.tw,rn. 015 cortisone.tw,rn. 016 exp prednisolone/ 017 prednisolon.tw,rn. 018 or/7‐17 019 6 and 18 020 clinical trial.pt. 021 randomized controlled trial.pt. 022 tu.fs. 023 dt.fs. 024 random$.tw. 025 (double adj blind$).tw. 026 placebo$.tw. 027 or/20‐26 028 19 and 27 029 28
Data and analyses
Comparison 1. Prednisone versus placebo.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Tender joint count | 5 | 304 | Mean Difference (IV, Fixed, 95% CI) | ‐2.14 [‐3.86, ‐0.43] |
| 2 Swollen joint count | 4 | 238 | Mean Difference (IV, Fixed, 95% CI) | ‐3.80 [‐6.74, ‐0.87] |
| 3 Grip strength | 1 | 66 | Mean Difference (IV, Fixed, 95% CI) | 35.0 [‐21.42, 91.42] |
| 4 ESR | 3 | 110 | Mean Difference (IV, Fixed, 95% CI) | ‐7.03 [‐18.06, 4.01] |
| 5 Pain | 2 | 162 | Mean Difference (IV, Fixed, 95% CI) | ‐0.31 [‐0.56, ‐0.06] |
| 6 Functional status | 1 | 128 | Mean Difference (IV, Fixed, 95% CI) | ‐0.39 [‐0.63, ‐0.15] |
1.1. Analysis.
Comparison 1 Prednisone versus placebo, Outcome 1 Tender joint count.
1.2. Analysis.
Comparison 1 Prednisone versus placebo, Outcome 2 Swollen joint count.
1.3. Analysis.
Comparison 1 Prednisone versus placebo, Outcome 3 Grip strength.
1.4. Analysis.
Comparison 1 Prednisone versus placebo, Outcome 4 ESR.
1.5. Analysis.
Comparison 1 Prednisone versus placebo, Outcome 5 Pain.
1.6. Analysis.
Comparison 1 Prednisone versus placebo, Outcome 6 Functional status.
Comparison 2. Prednisone versus aspirin.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Tender joint count | 1 | 77 | Mean Difference (IV, Fixed, 95% CI) | 1.30 [‐4.55, 7.15] |
| 2 ESR | 1 | 77 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [‐11.09, 11.09] |
2.1. Analysis.
Comparison 2 Prednisone versus aspirin, Outcome 1 Tender joint count.
2.2. Analysis.
Comparison 2 Prednisone versus aspirin, Outcome 2 ESR.
Comparison 3. Prednisone versus chloroquine.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Tender joint count | 1 | 56 | Mean Difference (IV, Fixed, 95% CI) | 2.40 [‐3.07, 7.87] |
| 2 Swollen joint count | 1 | 56 | Mean Difference (IV, Fixed, 95% CI) | 1.5 [‐0.32, 3.32] |
| 3 ESR | 1 | 56 | Mean Difference (IV, Fixed, 95% CI) | ‐16.0 [‐30.58, ‐1.42] |
| 4 Functional status | 1 | 56 | Mean Difference (IV, Fixed, 95% CI) | ‐0.20 [‐0.58, 0.18] |
3.1. Analysis.
Comparison 3 Prednisone versus chloroquine, Outcome 1 Tender joint count.
3.2. Analysis.
Comparison 3 Prednisone versus chloroquine, Outcome 2 Swollen joint count.
3.3. Analysis.
Comparison 3 Prednisone versus chloroquine, Outcome 3 ESR.
3.4. Analysis.
Comparison 3 Prednisone versus chloroquine, Outcome 4 Functional status.
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Empire 1995.
| Methods | Randomized, stratified by sex and centre Comparative Sample size at entry: Cortisone= 49, ASA = 50 | |
| Participants | Active polyarthritis of rheumatoid type Mean age: Cortisone = 46.0, ASA = 47.0 Disease Duration: Cortisone = 7.1 yrs, ASA = 6.8 yrs Mean number of affected joints: cortisone = 20.5, ASA = 18.0 | |
| Interventions | Cortisone acetate, initially 25 mg q 8 hrs, adjusted to the lowest effective dose. Therapy discontinued after 1 month if <=25 mg/d or => 100 mg/d. Average dose = ASA at 4 g/d in 5 daily doses | |
| Outcomes | Joint tenderness ESR | |
| Notes | Quality = 44% Chalmers scale Quality = 2/5 Jadad scale | |
Harris 1983.
| Methods | Randomized Placebo Double blind Sample size at entry: Prednisone= 18, placebo = 16 | |
| Participants | RA diagnosis of at least 1 year duration; active disease Mean age: Prednisone = 53.9, placebo = 54.9 % Female = 63% Mean disease duration: Prednisone = 6.9 yrs, placebo = 7.4 yrs Mean number affected joints: Prednisone = 28.1, placebo = 27.4 | |
| Interventions | Prednisone = 5 mg/day; placebo = 350 mg lactose NSAIDs, salicylates, gold salts, D‐penicillamine allowed | |
| Outcomes | Joint tenderness Joint swelling Pain ESR | |
| Notes | Quality = 56% Chalmers scale Quality = 4/5 Jadad scale | |
Kirwan 1995.
| Methods | Randomized Placebo controlled trial Double blind Sample size at entry: Prednisone = 61, placebo = 67 | |
| Participants | Active RA (based on # painful joints, active synovitis, AM stiffness, acute phase response) Disease duration < 2 years Mean age: Prednisone = 48.2, placebo = 50.3 % Female: Prednisone = 88%, placebo = 89% Disease duration: Prednisone = 1.28 yrs, placebo = 1.34 yrs Articular index: prednisone = 208, placebo = 209 | |
| Interventions | Prednisone 7.5 mg/day placebo = "identical tablets" NSAIDs and specific antirheumatic drugs allowed (Authors report similar rates of NSAID and other antirheumatic drug use among placebo and prednisone groups). | |
| Outcomes | Articular index (derived from both joint pain & swelling, weighted by joint size) Pain Functional status (HAQ) | |
| Notes | Quality = 5/5 Jadad scale | |
Million 1984.
| Methods | Randomized Placebo controlled Not blinded Sample size at entry: Prednisoline = 53, conservative rest = 50 | |
| Participants | Definite or classical RA by 1958 criteria Disease duration 2‐24 months Mean age: Prednisolone = 48, rest = 47.7 % Female: Prednisolone = 78%, rest = 83% # affected joints: Prednisolone = 10.3, rest = 10.7 | |
| Interventions | Prednisolone up to 20 mg/day adjusted to lowest effective dose Rest, conservative treatment Background drugs: ASA, NSAIDs, Chloroquine, Gold, intra‐articular steroids | |
| Outcomes | Joint tenderness Grip strength | |
| Notes | Quality = 15% Chalmers scale Quality = 2/5 Jadad scale | |
Stenberg 1992.
| Methods | Cross‐over Placebo controlled trial Double blinded Sample size at entry = 22 | |
| Participants | ACR criteria Active disease (defined by swollen & tender joints, ESR, AM stiffness and global pain) Mean age = 60.9 years % Female = 61% % RF positive = 100% Disease duration = 9.6 years (2‐22 years) | |
| Interventions | Prednisone 20 mg/d (days 1‐5), 10 mg/d (days 6‐10), 5 mg/d (days 11‐14) then adjust up during flares. Control = placebo tablets | |
| Outcomes | Joint tenderness Joint swelling ESR | |
| Notes | Quality = 28% Chalmers scale Quality = 2/5 Jadad scale | |
Van Gestel 1995.
| Methods | Crossover Placebo Sample size at entry: 22 | |
| Participants | Patients with RA, ACR criteria Mean age: 60.9 years (range 38‐77) % Female: 61% % RF positive: 18% Disease Duration: 9.6 years (2‐22) Patients excluded if DMARD or NSAID therapy changed in last 6 months | |
| Interventions | Prednisone 20 mg for 5 days, 10 mg for days 6‐10, 5 mg therafter adjusted upward to relieve symptoms Placebo Patients continued NSAID and DMARD treatment | |
| Outcomes | Joint tenderness Joint swelling ESR | |
| Notes | Quality = 38% Chalmers scale Quality = 2/5 Jadad scale | |
Van Schaardenburg 95.
| Methods | Randomized Comparative Sample size at entry: Prednisone= 28, chloroquine=28 | |
| Participants | Definite or classic RA (1958 ARA criteria) No concomitant DMARDs within previous 3 months Mean age: Pred= 69; Chlor=70 %Female: Prednisone= 71%; Chloroquine=63% % RF positive: Prednisone= 86%; Chloroquine=43% Disease duration: Prednisone= 11 months; Chloroquine= 10 months # affected joints: Prednisone=2.8; Chloroquine=3.7 | |
| Interventions | Chloroquine 100 mg/d loading dose, replaced with IM gold if lack of efficacy Prednisone dose: 15 mg/d, adjusted by 2.5 mg/week to lowest effective dose, add chloroquine if lack of efficacy after 3 months | |
| Outcomes | Joint tenderness (modified Ritchie Articular Index, max = 69) Joint swelling (max 20) ESR Functional status (Dutch HAQ) | |
| Notes | Quality = 52% Chalmers scale Quality = 2/5 Jadad scale | |
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Berntsen 1961 | Not randomized controlled trial |
| Boardmann 1967 | Inadequate treatment duration Non‐quantitative joint count measure(s) |
| Buchanan 1988 | Not randomized controlled trial Inadequate treatment duration |
| De Andrade 1964 | Inadequate treatment duration No joint swelling or tenderness |
| Deodhar 1973 | Inadequate treatment duration |
| Empire Cort 1957 | Continuation of earlier study |
| Gray 1991 | Deflazacort control |
| Healy 1988 | Not randomized controlled trial |
| Hench 1949 | Not randomized controlled trial No joint swelling or tenderness |
| Joint ACTH 1954 | Inadequate corticosteroid dose |
| Joint ACTH cort 1957 | Inadequate corticosteroid dose No joint swelling or tenderness Cortisone control |
| Joint ACTH pred 1959 | Non‐standard measure(s) of joint count No standard deviation available for other measures |
| Joint ACTH pred 1960 | No joint swelling or tenderness Continuation of earlier study |
| Joint ACTH2 1955 | Continuation of earlier study |
| Joint ACTH3 1957 | Continuation of earlier study |
| Lee 1973 | Inadequate treatment duration No joint swelling or tenderness |
| Lee 1976 | Not randomized controlled trial Inadequate treatment duration No joint swelling or tenderness Duplicate data |
| Lockie 1983 | Not randomized controlled trial No joint swelling or tenderness |
| McConkey 1973 | Not randomized controlled trial No joint swelling or tenderness |
| McConkey 1979 | Not randomized controlled trial No joint swelling or tenderness |
| McDougall 1994 | Not randomized controlled trial No joint swelling or tenderness |
| Messina 1992 | Deflazacort control |
| Myles 1976 | Not randomized controlled trial No joint swelling or tenderness |
| Ritchie 1968 | Inadequate treatment duration Non‐quantitative joint count measure(s) |
| Tait 1994 | Not randomized controlled trial |
| West 1967 | Continuation of earlier study |
| Zuckner 1969 | Not randomized controlled trial Inadequate corticosteroid dose |
Sources of support
Internal sources
Rosalind Russell Medical Research Center for Arthritis, UCSF, USA.
External sources
No sources of support supplied
Declarations of interest
None known
Edited (no change to conclusions)
References
References to studies included in this review
Empire 1995 {published data only}
- Empire Rheumatism Council Sub‐Committee. Multi‐Center controlled trial comparing cortisone acetate and acetyl salicylic acid in the long‐term treatment of rheumatoid arthritis. Ann Rheum Dis 1955;14:353‐363. [DOI] [PMC free article] [PubMed] [Google Scholar]
Harris 1983 {published data only}
- Harris, E. D., Emkey, R.D., Nichols, J.E., and Newberg, A. Low dose prednisone therapy in rheumatoid arthritis: A double blind study. J Rheumatol 1983;10:713‐721. [PubMed] [Google Scholar]
Kirwan 1995 {published data only}
- Kirwan, J. R., Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med 1995;333:142‐6. [DOI] [PubMed] [Google Scholar]
Million 1984 {published data only}
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Stenberg 1992 {published data only}
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