|Year : 2020 | Volume
| Issue : 1 | Page : 14-20
Effectiveness and safety study of oral triamcinolone in patients with rheumatoid arthritis in India
Department of Rheumatology, Lifepoint Multispecialty Hospital, Pimpri-Chinchwad, Maharashtra, India
|Date of Submission||21-Aug-2019|
|Date of Decision||21-Oct-2019|
|Date of Acceptance||14-Nov-2019|
|Date of Web Publication||13-Jan-2020|
Dr. Nilesh Patil
Department of Rheumatology, Lifepoint Multispecialty Hospital, 145/1 Mumbai Bypass Road, Near Hotel Sayaji, Wakad, Pimpri- Chinchwad - 411 023, Maharashtra
Source of Support: None, Conflict of Interest: None
INTRODUCTION: This study was conducted to assess the effectiveness and safety of low-dose oral triamcinolone (Kenacort®, Abbott Healthcare Pvt. Ltd) in combination with disease-modifying antirheumatic drugs (DMARDs) in Indian patients with rheumatoid arthritis (RA).
MATERIALS AND METHODS: Patients with an established diagnosis of RA, on a stable dose of DMARDs for at least 6-weeks, with evidence of disease flare-up or insufficient response to DMARDs were enrolled. Effectiveness of triamcinolone (4 mg) on disease activity (Disease Activity Score-28 [DAS28]), severity (Visual Analog Scale) and duration of morning stiffness, tender joint count (TJC), swollen joint count (SJC), patient global assessment of disease activity (Health Assessment Questionnaire-Disability Index [HAQ-DI]), quality of life (RAND 36-Item Health Survey score [SF-36]), and safety at 6 and 12 weeks of treatment were assessed.
RESULTS: About 98.3% of patients completed the study (119/121; female: 64.5%). A significant improvement in DAS28 score was evident at weeks 6 and 12 compared to baseline (baseline: mean [standard deviation (SD)]: 6.6 (0.9); week 6: mean (SD): 5.5 (0.9); 95% confidence interval difference (CI): −1.3 to −1.0; P < 0.001; week 12: mean [SD]:4.7 [0.7]; 95% CI difference: −2.1 to −1.8; P < 0.001). Severity and duration of morning stiffness also improved significantly at the end of 6 and 12 weeks of treatment (P < 0.001). Substantial improvement in TJC, SJC, HAQ-DI score, and RAND 36-Item score was also evident (P < 0.001). Commonly reported adverse events were gastroesophageal reflux disease (3.3%), headache (3.3%), and fever (2.5%), which were mild and resolved subsequently.
CONCLUSION: Low-dose triamcinolone with DMARDs was effective and well-tolerated in Indian patients with RA and in those with evidence of disease flare-up or insufficient response to DMARDs.
Keywords: Disease-modifying antirheumatic drugs, glucocorticoids, oral triamcinolone, rheumatoid arthritis, tender joint count
|How to cite this article:|
Patil N. Effectiveness and safety study of oral triamcinolone in patients with rheumatoid arthritis in India. Int J Health Allied Sci 2020;9:14-20
|How to cite this URL:|
Patil N. Effectiveness and safety study of oral triamcinolone in patients with rheumatoid arthritis in India. Int J Health Allied Sci [serial online] 2020 [cited 2020 Feb 24];9:14-20. Available from: http://www.ijhas.in/text.asp?2020/9/1/14/275652
| Introduction|| |
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease which damages cartilage, bones, and joints, resulting in degenerative changes, including loss of function and joint instability. The disease is three times more common in women compared to men and typical in elderly population., RA affects 0·5%–1·0% of all adults, with majority in the age group of 35–50 years. The global prevalence of RA varies between 0.3% and 1% amid an annual incidence rate of three cases per 10,000 population. The disease is ranked as the 42nd highest contributor to global disability. In India, the prevalence of RA is reported to be between 0.28% and 0.7%, translating into an adult patient population of 2.37–4.66 million.,
RA is characterized by synovial inflammation and hyperplasia (“swelling”), autoantibody production, cartilage and bone destruction (“deformity”), and systemic features including cardiovascular, pulmonary, psychological, and skeletal disorders. The interaction between environmental triggers and genetic factors are thought to influence the susceptibility of the disease., Patients with RA typically present with pain, stiffness in multiple joints, swollen peripheral joints, regional osteoporosis, narrowing of the synovial space, and fibrous ankylosis. Morning joint stiffness practically present in a majority of the patients with active RA is considered as one of the most characteristic diagnostic criteria of the disease. The degree of morning stiffness correlates with elevated levels of nocturnal pro-inflammatory cytokine interleukin-6 which shows a marked rise – above tenfold – in the early morning hours in patients of RA.
Early diagnosis and timely initiation of treatment are crucial for a more benign course of the disease. Treatment for RA is mainly focused on managing symptoms such as pain, stiffness, and mobility, to achieve stable remission and improve mobility. There are a number of disease-modifying and anti-inflammatory agents which can significantly reduce the impact of RA. The available medications for RA include glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs), targeted DMARDs, and biologic DMARDs.
Glucocorticoids used as monotherapy or in combination with conventional synthetic DMARDs have been an invaluable tool in the management of RA for decades., Glucocorticoids are not only effective in relieving signs and symptoms of the RA but also interfere with radiographic progression disease. The high-quality evidence has shown that glucocorticoid therapy reduces breakdown and erosion of cartilage and bones in the affected joints, as seen by X-rays over a period of 1–2 years.
However, concerns have been raised regarding adverse events (AEs) associated with long-term and/or high-dosage administration of glucocorticoids. Long-term systemic glucocorticoids are found to be associated with adverse effects such as adrenal suppression, hyperglycemia, diabetes, cardiovascular disease, dyslipidemia, dermatological and gastrointestinal events, psychiatric disturbances, and immunosuppression. In addition, longer duration and a higher dose of glucocorticoids in patients with RA are linked with increased risk of generalized bone loss, hip, and vertebral fractures.,
However, on the contrary, results from a large number of studies have indicated that a combination of low-dose glucocorticoids with DMARDs may have a significant benefit with respect to joint preservation, along with acceptable safety. Furthermore, there is evidence that long-term treatment with low-dose glucocorticoids slows down radiographic progression by at least 50% in patients with early RA. Low-dose glucocorticoids can aid in avoiding the occurrence of adverse effects caused by most DMARDs. This may also delay the use of expensive biologic agents for the management of RA.
It has been demonstrated that low-dose (4 mg) oral triamcinolone, a corticosteroid, reduced the early morning inflammatory surge in RA patients by at least 75% without adrenal insufficiency, salt retention, edema, obesity, moon face, hypertension, metabolic syndrome, infections, or mood disorders. Triamcinolone also resulted in weight loss and diuresis which aided recovery in patients with pain, inflammation, and disability.
However, there is a dearth of data to corroborate the effect of low-dose oral triamcinolone in RA patients. The present study was designed to obtain insights on the effect of low-dose oral triamcinolone as an adjunct to DMARDs in Indian patients with RA over a period of 24-weeks. Changes in disease activity and patient-reported outcomes (physical and emotional functions), in addition to the safety and side effect profile with once-daily 4 mg oral triamcinolone, were also assessed.
| Materials and Methods|| |
Study design and population
This was a prospective, single-center, open-label, noncomparative study (CTRI/2018/07/015000) evaluating the effectiveness and safety of oral low-dose triamcinolone as an add-on to DMARD therapy in Indian patients with RA. The study was conducted from July 2018 to January 2019 at the Department of Rheumatology, Lifepoint Multispecialty Hospital, Pimpri-Chinchwad, India.
- Male and female patients in the age group of 18-65 years.
- Patients willing to participate in the study and sign the informed consent form.
- Patients with a documented history of RA who are on treatment with at least one DMARD for >6 months and on a stable dose of DMARD(s) for at least 6 weeks.
- Patients with evidence of disease flare-up or having insufficient response to DMARD(s) defined as:
- DAS-28 (ESR) >3.2 (moderate disease activity),
- Swollen joint count of 4 or more out of 28,
- Tender joint count of 4 or more out of 28
Patients treated with glucocorticoids by any route in the past 6 weeks on more than 3 DMARDs or an additional concomitant biological DMARD, patients having other types of inflammatory arthritis (e.g., lupus), active infection including tuberculosis, uncontrolled diabetes, or uncontrolled hypertension, patients under treatment with any medication that may affect the treatment efficacy evaluation, patients under treatment with any medication whose concomitant use may be susceptible to interactions with triamcinolone or may affect the safety, patients having known intolerance to any of the ingredients of the formulation, inability, or unwillingness to comply with study procedures, patients having participated in a clinical trial in the past 30 days, pregnant or lactating women, and patients having any other condition deemed unfit by the investigator for the patients' participation in the study were excluded from the study.
The study duration was 24 weeks. During the 12-week treatment period, patients were prescribed with low-dose oral triamcinolone (Kenacort®, Abbott Healthcare Pvt. Ltd) as an add-on to their current DMARD therapy and were administered in the morning in nonfasting condition. Follow-up visits were scheduled at weeks 6, 12, and 24 (12 weeks after discontinuation of triamcinolone therapy), along with telephonic follow-ups at weeks 8 and 10, respectively. Patients were also provided with a diary to record details of daily study drug consumption, any AEs experienced, and concomitant medications consumed during the study.
The study was conducted in accordance with the principles of the Declaration of Helsinki and in compliance with Good Clinical Practice guidelines. Written informed consent was obtained from all study participants or legally acceptable representative of the patient before being examined for eligibility criteria. The study protocol and the informed consent form were reviewed and approved by the relevant institutional review board before initiation of the study.
Outcome measures for testing the efficacy of low-dose oral triamcinolone at baseline and follow-up visits included severity of morning stiffness on a 0–100 mm Visual Analog Scale (VAS, 0 = no pain and 100 = worst imaginable pain), duration of morning stiffness (min), TJC-28, SJC-28, DAS28-ESR, Health Assessment Questionnaire-Disability Index (HAQ-DI) score, and RAND 36-Item Health Survey (RAND SF-36) score.
Disease Activity Score-28-erythrocyte sedimentation rate
The DAS index combines information relating to the number of swollen and tender joints, in addition to a measure of general health and acute phase response. The DAS28 is based on a count of 28 swollen and tender joints, with a score ranging from 0 to 9.4, and can be used to objectively evaluate a patient's response to treatment.
The HAQ-DI includes eight blocks of questions covering difficulties when performing simple daily activities. The maximum score of all items within each of the eight categories gives the category score for each patient. The functional disability index is the average of all eight category scores.
The RAND SF-36 is a set of generic, coherent, and easily administered, patient-reported quality-of-life measure questionnaire. The scale is widely used for routine monitoring and assessment of treatment outcomes in adult patients.
The primary endpoints were percentage of patients achieving low DAS28-ESR score (DAS [ESR] ≤3.2) at week 12, mean change in DAS28-ESR, severity (VAS score [mm]), and duration of morning stiffness (min) from baseline to week 12, post low-dose triamcinolone plus DMARD treatment.
The secondary endpoints included percentage of patients achieving low DAS28-ESR score (DAS [ESR] ≤3.2) at weeks 6 and 24, percentage of patients achieving improved score (defined as ≥0.22 units improvement in the HAQ-DI) at 6 and 12 weeks, percentage of patients who required dose modification at 24 weeks (12 weeks after stopping treatment with low-dose triamcinolone), mean change in DAS28-ESR, severity (VAS score [mm]) and duration of morning stiffness (min) from baseline to week 6, and mean change in TJC-28, SJC-28, and RAND SF-36 scores from baseline to weeks 6 and 12, following treatment with low-dose triamcinolone as an adjunct to DMARD. Safety was also assessed throughout the study period.
Qualitative and quantitative variables are presented using descriptive statistics. Quantitative variables were evaluated using paired t-test at 5% level of significance, and the corresponding P value is presented. Data were analyzed using SPSS® statistics software, version 23.0 (IBM Corp., Armonk, NY, USA).
| Results|| |
A total of 121 (men: 43; women: 78) patients with mean (standard deviation [SD]) age of 45.5 (11.7) years were enrolled in the study. Of the 121 patients, 119 (98.3%) completed the study; two patients withdrew consent to participate in the study. The demographic and baseline characteristics of patients are summarized in [Table 1].
Of 119 patients who completed the study, 6 (5.0%) and 15 (12.6%) patients achieved low DAS-28 score (DAS [ESR] ≤3.2) at weeks 6 and 12, respectively, post triamcinolone plus DMARD treatment. Five (4.2%) patients maintained a low DAS-28 score (DAS [ESR] ≤3.2) at 24 weeks, i.e., 12 weeks after discontinuing treatment.
The mean change in efficacy parameters at weeks 6 and 12, post treatment, is presented in [Table 2]. Compared to the mean (SD) score of 6.6 (0.9) at baseline, DAS-28 score reduced significantly by −1.1 and −1.9 at weeks 6 and 12, respectively. The mean (SD) morning stiffness (VAS score) reduced significantly by −8.4 at week 6 and by −17.4 at 12 weeks, compared to the mean (SD) baseline score of 62.5 (13.8). Likewise, duration of morning stiffness (min) reduced significantly by −6.3 min and −8.0 min at weeks 6 and 12, respectively, compared to the baseline mean (SD) duration of 31.7 (12.1) min.
|Table 2: Mean change in efficacy parameters after 6 weeks and 12 weeks of treatment compared to baseline|
Click here to view
The mean (SD) TJC-28 score at baseline was 20.6 (5.0), which reduced significantly by −9.8 at week 6 and by −13.5 at 12 weeks. Similarly, the mean SJC-28 scores reduced significantly by −6.7 and −12.2 at weeks 6 and 12, respectively, compared to the baseline mean (SD) score of 16.5 (5.8) [Table 2]. The mean (SD) HAQ-DI score at the baseline was 1.6 (0.4), which reduced significantly by −0.5 and −0.6 at weeks 6 and 12, respectively [Table 2]. Correspondingly, a total of 94 (79.0%) and 108 (90.8%) patients achieved a reduction of ≥0.22 units in HAQ-DI score at weeks 6 and 12, respectively.
[Table 3] presents the mean changes in scores of RAND SF-36 parameters at weeks 6 and 12, post treatment. Compared to the baseline mean (SD) score of 33.4 (14.0), physical function score increased significantly by 20.9 and 32.5 at weeks 6 and 12, respectively. The mean (SD) score for role limitation due to physical health at the baseline was 10.9 (19.4), which improved significantly by 16.9 at week 6 and by 42.8 at 12 weeks. Likewise, the mean (SD) score for role limitation due to emotional health at the baseline was 9.5 (19.9), which increased significantly by 17.6 at week 6 and by 44.5 at 12 weeks.
|Table 3: Mean change in RAND 36-Item Health Survey score parameters after 6 weeks and 12 weeks of treatment compared to baseline|
Click here to view
The mean energy score increased significantly by 8.3 and 6.1 at weeks 6 and 12, respectively, compared to the baseline mean (SD) score of 43.9 (8.5). However, compared to the baseline mean (SD) score of 50.1 (9.5), emotional well-being score declined significantly by −3.4 at week 6 and by −3.0 at 12 weeks. The mean (SD) social function score at the baseline was 45.6 (9.5), which increased by 1.9 and 1.1 at weeks 6 and 12, respectively, though not significant [Table 3].
The mean pain score improved significantly by 14.7 at week 6 and by 22.5 at 12 weeks, compared to the baseline mean (SD) score of 38.8 (14.6). The mean (SD) general health score at the baseline was 53.9 (16.3), which decreased significantly by −6.7 at week 6. The mean health change score improved significantly by 19.4 and 26.9 at weeks 6 and 12, respectively, compared to the baseline mean (SD) score of 26.7 (13.3) [Table 3].
About 13 (10.7%) patients reported incidences of AEs. Most commonly reported AEs were gastroesophageal reflux disease (GERD; 4 [3.3%]) and headache (4 [3.3%]), followed by fever (3 [2.5%]) and mild pain (2 [1.7%]). Majority of AEs were mild in nature, which were resolved subsequently, and were not due to study medication. No severe or serious AEs were reported.
| Discussion|| |
Glucocorticoids are potent anti-inflammatory drugs used in patients with RA to bridge the time until treatment with DMARDs is effective., Glucocorticoids have a long history of use in the treatment of RA. The most commonly available glucocorticoids include dexamethasone, methylprednisolone, prednisolone, prednisone, and triamcinolone. Co-administration of low-dose glucocorticoids with DMARDs as “bridging therapy” in RA treatment is now widely accepted. A meta-analysis by Kirwan et al. in 2007 had established that glucocorticoids at low doses slow the progression of joint damage in RA. These findings have paved the way for European and US rheumatology associations to review their position, especially in the treatment of early RA.,
Triamcinolone has been used in the treatment of RA for over 6 decades. It suppresses inflammation and rheumatic manifestations while having fewer and less severe gastrointestinal symptoms, less psychic irritation, and no effect on arterial blood pressure. However, there is a lack of scientific evidence to evaluate the safety and efficacy of low-dose (4 mg) oral triamcinolone in RA patients. The present study evaluated the effectiveness and safety of low-dose oral triamcinolone as an adjunct to DMARDs in Indian patients with RA over an observation period of 24 weeks. To the best of our knowledge, this is the first of its kind study evaluating the effect of low-dose oral triamcinolone in RA patients in the past 3 decades.
The DAS28-ESR based on 28 joints is an important tool for assessing disease activity and treatment success in achieving desired disease control. The most commonly used evaluation in daily practice, DAS28-ESR, has been validated in clinical trials to assess treatment response in RA patients. In our study, 15 (12.6%) patients achieved low disease activity (defined as having a DAS-28 ≤ 3.2) at week 12, following low-dose triamcinolone plus DMARD treatment. The mean DAS-28 score also reduced significantly (P< 0.0001) by −1.9 at week 12. This reduction in DAS-28 score was comparable to change in DAS-28 score of −1.15 reported by Buttgereit et al. Circadian Administration of Prednisone in Rheumatoid Arthritis (CAPRA-2) with low-dose prednisone at 12 weeks, and higher than −0.9 reported by Cutolo et al., with modified-release prednisone at 16 weeks.
Functional disability and pain arising from morning stiffness have a significant impact on patients' quality of life. In this study, a trend toward lower severity and duration of morning stiffness was noted. The mean morning stiffness reduced significantly (P< 0.0001) by −17.4 at 12 weeks, and duration of morning stiffness reduced significantly by −8.0 min by week 12.
Swollen and tender joints are the most characteristic features of RA, and disease severity is directly related to the SJC and TJC. In our study, TJC-28 score decreased significantly (P< 0.0001) by −13.5 and SJC-28 score by −12.2 at 12 weeks, post low-dose triamcinolone plus DMARD treatment. The change in TJC and SJC scores reported in our study was comparatively higher than change in TJC score of −4.7 and SJC score of −3.3 reported by Buttgereit et al. (CAPRA-2), with low-dose prednisone at 12 weeks.
The HAQ-DI is a standardized disability questionnaire developed for use in RA. A high HAQ-DI score has been reported to be a strong predictor of morbidity and mortality in RA, and low HAQ-DI scores are predictive of better outcomes. There was a significant decrease in HAQ-DI scores in our study, following treatment with low-dose triamcinolone and DMARD. The mean HAQ-DI score reduced significantly (P< 0.0001) by −0.6 at 12 weeks. Correspondingly, a total of 108 (90.8%) patients achieved a reduction of ≥0.22 units in HAQ-DI score at week 12. This reduction of −0.6 in HAQ-DI score in our study was comparatively higher than the change in HAQ-DI score of −0.24 reported by Buttgereit et al. (CAPRA-2), with low-dose prednisone at 12 weeks.
RAND 36-Item Health Survey has the advantage of describing the impact of the disease in terms of patient-centered outcomes rather than the biological or disease-centered outcomes perceived by clinicians. The RAND SF-36 includes eight scales that assess pain, physical functioning, general health, fatigue/vitality, mental health, social functioning, and role limitations due to either physical or emotional problems, assessing a broader range of health concerns than RA-specific measures, and has had extensive testing of reliability and validity.
In our study, compared to the baseline scores of physical functioning, role limitations – physical health and emotional problem, energy, pain, and health change components of the RAND SF-36 scale improved significantly (P< 0.0001) at the follow-up visits [Table 3]. However, general health, social functioning, and emotional well-being scores showed a weak response. Mean general health and social function scores increased marginally (P > 0.05) by 1.2 and 1.1, respectively, at 12 weeks; with emotional well-being score declining significantly (P< 0.05) by −3.0 at 12 weeks, post treatment [Table 3]. Although antirheumatic treatments improve the core physical aspects of RA and induce large changes in the pain and physical functioning scales, they do not directly target mood or social functioning. The effects on these aspects of health are indirect. Likewise, changes in general health and social function scores in our study were small relative to the changes in physical measures.
The RAND SF-36 scale deals with aspects of health status other than pain and physical functioning in RA patients. The results from our study indicated that diminished general health and social functioning scores have an impact on the overall emotional well-being of RA patients. It can be comprehended that the impact of disease in RA patients is not limited to physical domains but affects their mental and emotional well-being.
The AEs observed in our study were fewer when compared with AEs reported in other studies with short-term,, and long-term, use of low-dose glucocorticoids. No severe or serious AEs were reported. The most commonly reported AEs in our study were GERD, headache, and fever.
In this single-center, open-label, prospective study, a 12-week treatment with low-dose triamcinolone plus DMARD was found to produce significant and clinically relevant improvements in DAS28-ESR, severity and duration of morning stiffness, SJC, TJC, and HAQ-DI scores, with a safety profile comparable to conventional glucocorticoids formulation. The effect of low-dose triamcinolone treatment was visible at 24 weeks that is 12 weeks after terminating therapy.
The use of lower doses of GCs (<5 mg/d) has gained recognition by primary care providers and rheumatologists as both a “bridge” and an alternative to slow-acting antirheumatic drugs, DMARD, and nonsteroidal anti-inflammatory drugs. Recommendations have also indicated that glucocorticoids, especially at low doses and for a short duration, remain an appropriate option for RA treatment.,
| Conclusion|| |
The results from our study suggest that low-dose triamcinolone adjunct to DMARD was well tolerated, convenient to administer, and produced a clinically relevant improvement in RA symptoms. The present data also provide support for the use of low-dose triamcinolone as an adjunct to the DMARD in patients with early RA. However, small sample size, nonstatistically powered, and absence of control and/or comparator group are some limitations of this study. Further, large-scale randomized controlled studies are warranted to substantiate the results.
The authors thank the patients and study teams involved in the study. The authors also thank medONE Pharma Solutions, Delhi NCR, India, for medical writing support for the development of the manuscript.
Financial support and sponsorship
This investigator-initiated study was funded by Abbott Healthcare Pvt. Ltd, Mumbai, India.
Conflicts of interest
There are no other conflicts of interest.
| References|| |
Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet 2016;388:2023-38.
Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet 2010;376:1094-108.
Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T, et al
. The global burden of rheumatoid arthritis: Estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73:1316-22.
Handa R, Rao UR, Lewis JF, Rambhad G, Shiff S, Ghia CJ. Literature review of rheumatoid arthritis in India. Int J Rheum Dis 2016;19:440-51.
Handa R, Chaturvedi V, Danda D, Krishnamurthy V. Pneumococcal vaccination in rheumatic diseases. J Assoc Physicians India 2015;63:40-2.
Gibofsky A. Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: A synopsis. Am J Manag Care 2014;20:S128-35.
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N
Engl J Med 2011;365:2205-19.
Magyari L, Varszegi D, Kovesdi E, Sarlos P, Farago B, Javorhazy A, et al
. Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications. World J Orthop 2014;5:516-36.
Cutolo M, Villaggio B, Otsa K, Aakre O, Sulli A, Seriolo B. Altered circadian rhythms in rheumatoid arthritis patients play a role in the disease's symptoms. Autoimmun Rev 2005;4:497-502.
Arvidson NG, Gudbjörnsson B, Elfman L, Rydén AC, Tötterman TH, Hällgren R. Circadian rhythm of serum interleukin-6 in rheumatoid arthritis. Ann Rheum Dis 1994;53:521-4.
Fidahic M, Jelicic Kadic A, Radic M, Puljak L. Celecoxib for rheumatoid arthritis. Cochrane Database Syst Rev 2017;6:CD012095.
National Collaborating Centre for Chronic Conditions (UK). Rheumatoid Arthritis: National Clinical Guideline for Management and Treatment in Adults. (NICE Clinical Guidelines, No. 79.). London: Royal College of Physicians (UK); February, 2009. Available from: https://www.ncbi.nlm.nih.gov/books/NBK51812/
. [Last accessed on 2019 Apr 26].
Gibofsky A. Current therapeutic agents and treatment paradigms for the management of rheumatoid arthritis. Am J Manag Care 2014;20:S136-44.
Cutolo M, Spies CM, Buttgereit F, Paolino S, Pizzorni C. The supplementary therapeutic DMARD role of low-dose glucocorticoids in rheumatoid arthritis. Arthritis Res Ther 2014;16 Suppl 2:S1.
Krause D, Rau R, Braun J. Glucocorticoid treatment in early rheumatoid arthritis. Clin Exp Rheumatol 2011;29:S121-5.
Svensson B, Boonen A, Albertsson K, van der Heijde D, Keller C, Hafström I. Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: A two-year randomized trial. Arthritis Rheum 2005;52:3360-70.
Kirwan JR, Bijlsma JWJ, Boers M, Shea B. Effects of glucocorticoids on radiological progression in rheumatoid arthritis. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD006356. DOI: 10.1002/14651858.CD006356.
Kavanaugh A, Wells AF. Benefits and risks of low-dose glucocorticoid treatment in the patient with rheumatoid arthritis. Rheumatology (Oxford) 2014;53:1742-51.
Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, et al
. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol 2013;9:30.
Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. J Bone Miner Res 2000;15:993-1000.
Kim D, Cho SK, Park B, Jang EJ, Bae SC, Sung YK. Glucocorticoids are associated with an increased risk for vertebral fracture in patients with rheumatoid arthritis. J Rheumatol 2018;45:612-20.
Bijlsma JW. Disease control with glucocorticoid therapy in rheumatoid arthritis. Rheumatology (Oxford) 2012;51 Suppl 4:iv9-13.
Roger L. Where in the world is oral triamcinolone? J Rheumatol 2011;38:1519.
Hoes JN, Jacobs JW, Buttgereit F, Bijlsma JW. Current view of glucocorticoid co-therapy with DMARDs in rheumatoid arthritis. Nat Rev Rheumatol 2010;6:693-702.
Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al
. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960-77.
Nikas NS. Long-term treatment with low dose glucocorticoids in rheumatoid arthritis: New tricks of an old drug. Mediterr J Rheumatol 2018;29:13-6.
Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, et al
. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2016;68:1-26.
Hartung EF. Triamcinolone in treatment of rheumatoid arthritis. J Am Med Assoc 1958;167:973-6.
Canhão H, Rodrigues AM, Gregório MJ, Dias SS, Melo Gomes JA, Santos MJ, et al
. Common evaluations of disease activity in rheumatoid arthritis reach discordant classifications across different populations. Front Med (Lausanne) 2018;5:40.
Buttgereit F, Mehta D, Kirwan J, Szechinski J, Boers M, Alten RE, et al
. Low-dose prednisone chronotherapy for rheumatoid arthritis: A randomised clinical trial (CAPRA-2). Ann Rheum Dis 2013;72:204-10.
Cutolo M, Iaccarino L, Doria A, Govoni M, Sulli A, Marcassa C. Efficacy of the switch to modified-release prednisone in rheumatoid arthritis patients treated with standard glucocorticoids. Clin Exp Rheumatol 2013;31:498-505.
Buttgereit F, Doering G, Schaeffler A, Witte S, Sierakowski S, Gromnica-Ihle E, et al
. Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): A double-blind, randomised controlled trial. Lancet 2008;371:205-14.
Scott IC, Scott DL. Joint counts in inflammatory arthritis. Clin Exp Rheumatol 2014;32:S7-12.
Sultan N, Pope JE, Clements PJ; Scleroderma Trials Study Group. The health assessment questionnaire (HAQ) is strongly predictive of good outcome in early diffuse scleroderma: Results from an analysis of two randomized controlled trials in early diffuse scleroderma. Rheumatology (Oxford) 2004;43:472-8.
Talamo J, Frater A, Gallivan S, Young A. Use of the short form 36 (SF36) for health status measurement in rheumatoid arthritis. Br J Rheumatol 1997;36:463-9.
Ward MM, Guthrie LC, Alba MI. Clinically important changes in short form 36 health survey scales for use in rheumatoid arthritis clinical trials: The impact of low responsiveness. Arthritis Care Res (Hoboken) 2014;66:1783-9.
Buttgereit F, Doering G, Schaeffler A, Witte S, Sierakowski S, Gromnica-Ihle E, et al
. Targeting pathophysiological rhythms: Prednisone chronotherapy shows sustained efficacy in rheumatoid arthritis. Ann Rheum Dis 2010;69:1275-80.
Rice JB, White AG, Scarpati LM, Wan G, Nelson WW. Long-term systemic corticosteroid exposure: A systematic literature review. Clin Ther 2017;39:2216-29.
Safy M, Jacobs J, IJff N. On behalf of the Society for Rheumatology Research Utrecht (SRU), long-term outcome is better when a methotrexate-based treatment strategy is combined with 10 mg prednisone daily: Follow-up after the second Computer-Assisted Management in Early Rheumatoid Arthritis trial. Ann Rheum Dis 2017;76:1432-5.
Palmowski Y, Buttgereit T, Dejaco C, Bijlsma JW, Matteson EL, Voshaar M, et al
. “Official View” on glucocorticoids in rheumatoid arthritis: A systematic review of International Guidelines and consensus statements. Arthritis Care Res (Hoboken) 2017;69:1134-41.
[Table 1], [Table 2], [Table 3]