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Yoon: Clinical Experience with Low-dose Modified-release Prednisone Chronotherapy in Asian Patients with Rheumatoid Arthritis in Singapore
Original Article

J Rheum Dis 2015;22(2):76-84.

Published online: 31 October 2015

DOI: https://doi.org/10.4078/jrd.2015.22.2.76

Clinical Experience with Low-dose Modified-release Prednisone Chronotherapy in Asian Patients with Rheumatoid Arthritis in Singapore

Kam Hon Yoon

El Shaddai Arthritis and Rheumatism Specialist Medical Center, Singapore, Singapore

Corresponding to: Kam Hon Yoon, El Shaddai Arthritis and Rheumatism Specialist Medical Centre, Block 102, Towner Road #01-258, Singapore 322102, Singapore. E-mail: elshaddaiclinic@gmail.com

Received 11 July 2014       Revised 10 November 2014       Accepted 13 December 2014

Copyright © 2015 The Korean College of Rheumatology

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

To examine the demographic profile and treatment patterns in patients with rheumatoid arthritis (RA) prescribed low-dose modified-release prednisone (LODOTRAⓇ) on a named patient basis in Singapore and to evaluate safety and clinical outcome of the treatment.

Methods

Medical records of adult patients with RA who had inadequate responses to prior RA treatment and were prescribed low-dose modified-release prednisone between January and December 2012 at a specialist clinic were reviewed retrospectively. Demographics, treatment information, relevant laboratory evaluations, and disease condition, prior to and after the start of treatment, were collected.

Results

Thirty-eight patients were enrolled. The mean age was 52.8 years and median disease duration was 1.3 years (0.04 to 8.2 years). Patients received a mean daily dose of 5.0±1.0 mg of modi-fied-release prednisone for a median period of 4.4 months (0.2 to 11.8 months). Before treatment, the majority of patients received disease-modifying anti-rheumatic drugs (78.9%), glucocorticoids (71.0%), and non-steroidal anti-inflammatory drugs (NSAIDs) (68.4%). After the start of treatment, prescription of NSAIDs declined from 68.4% to 28.9%. Similar laboratory findings were observed before and after treatment. The median C-reactive protein level decreased substantially from 9.8 mg/L (0.2 to 77.7 mg/L) to 3.9 mg/L (0.4 to 27.6 mg/L). High proportions of patients reported improvement or recovery from morning stiffness (94.7%) or joint pain (70.0 to 100.0%) after treatment. The median number of painful joints decreased from 4 (1 to 8) to 0 (0 to 4) after treatment.

Conclusion

Our clinical experience in Asian patients with RA suggests that low-dose modified-release prednisone chronotherapy is associated with similar treatment patterns, safety profile, and clinical outcomes as in Western populations.

Keywords: Rheumatoid arthritis, Prednisone, Chronotherapy, Asians, Singapore

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Figure 1.
Prescription of maintenance medication among patients with rheumatoid arthritis before and after the start of low-dose modified-release prednisone chronotherapy. DMARDs: disease modifying anti-rheumatic drugs, NSAIDs: nonsteroidal anti-inflammatory drugs.
jrd-22-76f1.tif
Figure 2.
Course of disease condition after the start of low-dose modified-release prednisone chronotherapy compared to baseline. *Among patients with morning stiffness or pain at baseline.
jrd-22-76f2.tif
Table 1.
Demographics and baseline clinical characteristics (n=38)
Characteristic  
Age (yr) 52.8±12.8
Female 35 (92.1)
Race  
  Chinese 22 (57.9)
  Indian 13 (34.2)
  Malay 3 (7.9)
Disease duration since diagnosis (yr) 1.3 (0.04∼8.2)
Morning stiffness 19 (50.0)
Joint pain 38 (100.0)
  Total number of painful joints 4 (1∼8)
  Shoulder pain 15 (39.5)*
    Left 8 (21.1)
    Right 12 (31.6)
  Elbow pain 11 (28.9)*
    Left 6 (15.8)
    Right 9 (23.7)
  Wrist pain 12 (31.6)*
    Left 7 (18.4)
    Right 7 (18.4)
  Finger pain 24 (63.2)*
    Left 16 (42.1)
    Right 19 (50.0)
  Knee pain 27 (71.1)*
    Left 20 (52.6)
    Right 20 (52.6)
  Ankle pain 15 (39.5)*
    Left 10 (26.3)
    Right 8 (21.1)
  Other sites 12 (31.6)

Values are presented as mean±standard deviation, number (%), or median (range).

* Patients can have pain on the left side only, right side only or on both right and left sides.

Table 2.
Maintenance medications prescribed
Maintenance medications for RA (dosage) At baseline After start of treatment
Number (%) Median (range) Number (%) Median (range)
DMARDs 30 (78.9)   28 (73.7)  
 Hydroxychloroquine (mg/d) 21 (55.3) 266.7 (200.0∼400.0) 20 (52.6) 200.0 (200.0∼300.0)
 Methotrexate (mg/wk) 20 (52.6) 8.8 (5.0∼12.5) 22 (57.9) 10.0 (5.0∼15.0)
 Leflunomide (mg/wk) 7 (18.4) 100.0 (100.0∼100.0) 3 (7.9) 100.0 (100.0∼100.0)
 Sulfasalazine (mg/d) 5 (13.2) 1,000.0 (1,000.0∼1,000.0) 3 (7.9) 1,000.0 (1,000.0∼1,000.0)
 Minocycline (mg/d) 3 (7.9) 100.0 (100.0∼100.0) 3 (7.9) 100.0 (100.0∼100.0)
NSAIDs 26 (68.4)   11 (28.9)  
 Celecoxib (mg/d) 16 (42.1) 350.0 (200.0∼400.0) 6 (15.8) 350.0 (200.0∼400.0)
 Etoricoxib (mg/d) 12 (31.6) 102.5 (90.0∼120.0) 7 (18.4) 120.0 (90.0∼120.0)
Glucocorticoid-prednisone (mg/d) 27 (71.0) 8.3 (5.0∼16.3) 4 (10.5) 10.0 (5.0∼11.7)
Biologics 9 (23.7)   11 (28.9)  
 Etanercept (mg/mo) 8 (21.1) 25.0 (12.5∼100.0) 11 (28.9) 25.0 (8.3∼100.0)
 Adalimumab (mg/mo) 1 (2.6) 40.0 (40.0∼40.0) 1 (2.6) 20.0 (20.0∼20.0)
 Golimumab (mg/mo) 1 (2.6) 25.0 (25.0∼25.0) 1 (2.6) 50.0 (50.0∼50.0)

DMARDs: disease modifying anti-rheumatic drug, d: day, mo: month, NSAIDs: non-steroidal anti-inflammatory drugs, RA: rheumatoid arthritis, wk: week.

Table 3.
Flare medications prescribed
Flare medications for RA At baseline After start of treatment
Yes 25 (65.8) 28 (73.7)
 NSAIDs    
  Ketorolac 7 (18.4) 5 (13.2)
  Diclofenac 5 (13.2) 2 (5.3)
  Naproxen and esomeprazole 1 (2.6) 0
 Glucocorticoids    
  Betamethasone 25 (65.8) 25 (65.8)
  Triamcinolone 12 (31.6) 9 (23.7)
  Dexamethasone 0 1 (2.6)
 No 13 (34.2) 10 (26.3)

Values are presented as number (%). NSAIDs: non-steroidal anti-inflammatory drugs, RA: rheumatoid arthriitis.

Table 4.
Laboratory test findings before and after the start of low-dose modified-release prednisone chronotherapy
Laboratory finding Before treatment After start of treatment
Fasting glucose level (mg/dL) 92.5 (70.0∼216.0) 99.0 (67.0∼156.0)
  Abnormal* 4 4
  Normal 24 12
  Unknown 10 22
Triglyceride level (mg/dL) 100.0 (24.0∼314.0) 88.0 (34.2∼225.0)
  Abnormal* Not determined 2
  Normal Not determined 7
  Unknown 11 29
Total cholesterol level (mg/dL) 196.0 (126.0∼303.0) 218.0 (108.5∼314.0)
  Abnormal* Not determined 2
  Normal Not determined 7
  Unknown 11 29
ALT (U/L) 16.0 (8.0∼123.0) 19 (9.0∼87.0)
  Abnormal* 1 0
  Normal 27 16
  Unknown 10 29
AST (U/L) 24.5 (14.0∼66.0) 22.0 (14.0∼75.0)
  Abnormal* 0 0
  Normal 28 16
  Unknown 10 29

Values are presented as median (range) or number only. ALT: alanine aminotransferase, AST: aspartate aminotransferase.

* Abnormal laboratory findings: fasting glucose ＞120 mg/dL, 20% increase from baseline for triglycerides and total cholesterol, ALT＞102 U/L, AST＞81 U/L.

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