Article Text

PDF
THU0176 Efficiency and safety of rapamycin combined with low-dose IL-2 treatment compared with methotrexate in patients with rheumatoid arthritis
  1. Z Li1,
  2. H Niu1,
  3. M Chen1,
  4. H Yao1,
  5. J Luo1,
  6. C Gao2,
  7. X Li1,
  8. C Wang1
  1. 1Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
  2. 2Pathology, Brigham and Women's Hospital, Harvard Medical School, Brigham and Women's Hospital, Harvard Medical School, United States

Abstract

Background The molecular target rapamycin (mTOR) signaling can regulate between effector and regulatory T cell lineage commitment [1]. Rapamycin, the inhibitor of mTOR, has appeared to be a new therapy for several autoimmune diseases, such as systemic lupus erythematosus [2].

Objectives To evaluate whether rapamycin is beneficial in patients with Rheumatoid Arthritis (RA), and compared with Methotrexate in efficiency and safety.

Methods Fifty-eight DMARDs-naive RA patients were enrolled, thirty-eight were treated with Rapamycin (0.5 mg every 2 days, combined with IL-2 50WIU per day for 5 days), the others with Methotrexate (10mg per week) taken as control. Clinical improvement and immunological assessments were performed at baseline, 1 and 12 weeks. Treatment group assessed CD4+ T cell subsets by flow cytometry at baseline, 1 and 12 weeks.

Results We enrolled 58 patients. At baseline, patients had a mean DAS28 of 3.34 (0.81). Rapamycin group and Methotrexate group included 38 and 20 patients, respectively, with no significant differences in baseline characteristics. At 1 week, the mean DAS28 after Rapamycin treatment (2.43 [0.77]) and Methotrexate (2.25 [0.86]) was not significantly different (P=0.43). Same as ESR (24.74 [24.53], 21.76 [24.27], P=0.66). The dose of glucocorticoid during hospitalization of rapamycin treatment group (720.8 [554.3]) was lower than Methotrexate (1202.3 [943.1], P=0.042). The length of hospital stay of Rapamycin (14.5 [3.9]) was lower than Methotrexate (21.0 [3.8], P<0.001). Rapamycin administration resulted in an increase in the absolute counts of Treg cells from a median of 36.82 cell/ul (at week 0) to 99.80 cell/ul (at week 1) (P<0.001). The ratios of Th17/Treg cells showed a reduction from a median of 0.16 to 0.09, and the difference was significant (P=0.047). At 12 week, 5 patients treated with Rapamycin dropped out because of non-compliance. the mean DAS28 was not significantly different (2.36 [0.97], 2.16 [0.86], P=0.51). The same as the daily dose of glucocorticoid (10.21 [32.3], 9.16 [40.1], P=0.804). The absolute counts of Treg cells increased from a median of 36.82 cell/ul (at baseline) to 43.26 cell/ul after Rapamycin administration (P=0.028). The ratios of Th17/Treg had no significant difference from a median of 0.16 at baseline to 0.12 at week 12 (P=0.937). Liver enzyme elevations occurred on 2 patients after Methotrexate therapy for 1 week. However, there were no serious adverse events observed during the 12-week period of rapamycin treatment.

Conclusions Rapamycin combined with the low-dose IL-2 appears to be a safe and effective therapy for RA, by a rapid increase of circulating Treg cells and a correction of the ratio of Th17/Treg cells, which has gotten a same response compared with Methotrexate.

References

  1. Zheng Y. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment.[J]. Immunity, 2009, 30(6):832–844.

  2. Fernandez D, Bonilla E, Mirza N, et al. Rapamycin Reduces Disease Activity and Normalizes T Cell Activation–Induced Calcium Fluxing in Patients With Systemic Lupus Erythematosus[J]. Arthritis & Rheumatology, 2006, 54(9):2983–2988.

References

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.