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  1. F. R. Spinelli1,
  2. C. Garufi1,
  3. S. Mancuso1,
  4. F. Ceccarelli1,
  5. S. Truglia1,
  6. F. Conti1
  1. 1Sapienza University of Rome, Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Rheumatology Unit, Roma, Italy


Background The 2022 updated EULAR recommendations for the management of Rheumatoid Arthritis (RA) suggest tapering and discontinuation of oral glucocorticoids (GC), as rapidly as clinically feasible [1]. Considering GC as a “bridging therapy” to promptly reduce symptoms and control inflammation until the maximum effect of the Disease Modifying Anti-Rheumatic Drugs (DMARDs) is reached, the rapid effect of Janus Kinase (JAK) inhibitors could allow a fast and safe tapering of GC.

Objectives We aimed to evaluate the steroid-sparing effect of adding tofacitinib in RA patients with inadequate response to MTX.

Methods In this open label study, we enrolled patients with moderate-to-severe RA, on stable prednisone dose (5-12.5 mg/day) starting tofacitinib. After 1 month, in patients achieving at least a moderate EUALR response (>1.2 points reduction in DAS28 score), GC was tapered according to pre-specified schedule until complete withdrawal at week-12. The sample size of 30 patients was estimated assuming a 12-weeks response rate of 30% with a confidence interval of 90% and a margin of error of 15%. Disease activity was assessed after 4, 12, 24 and 48 weeks of treatment. The primary endpoint of the study was the percentage of patients discontinuing GCs after 12 weeks of treatment with tofacitinib. Secondary endpoints were: 1) the percentage of patients requiring a new GC course during the 12-months follow-up, 2) the percentage of patients in clinical remission or low disease activity at week 12, 24 and 48.

At each visit laboratory tests, complete physical examination and other safety assessments were performed with particular interest to serious infections, Varicella Zoster virus reactivation, Major Cardiovascular Adverse Events (MACE), thromboembolic events and malignancy. Adverse events leading withdrawal of tofacitinib were also recorded.

Results We enrolled 30 patients (26F: 4M, mean age 60±13 years, mean disease duration 13.2±7.8 years). The primary endpoint was achieved: 9 patients (30%) discontinued GC at week-12. At week 24 and 48, 12 patients (40%) had discontinued prednisone. The median prednisone dose decreased from a median dose of 5 mg/day (interquartile range 5-10 mg) to 2.5 (0-5), 2.5(0-5) mg/day at week 12 and 48 (p<0.00001 vs baseline). Multivariate analysis showed that factors negatively associated with GC withdrawal after 12 weeks were age (p=0.014), disease duration (p=0.045), and baseline PGA (p=0.028). During the follow up 4 patients had to increase the dose of GC from 1.2 (IQR 1-25-2.5) to 5; one more patient had to reintroduce 5 mg of prednisone after stopping at week 12. Discontinuation of glucocorticoids did not affect target achievement at week 12: a similar percentage of patients who discontinued or not discontinued GC achieved remission or low disease activity at week 12 (Figure 1A), and the percentage of patients who achieved the target increased throughout follow-up with no difference according to glucocorticoid therapy (Figure 1B).

Three out of the 30 patients discontinued tofacitinib for adverse events (one for the onset of endometrial malignancy after 5 months of treatment, one for serious infection and one for paresthesia). As for the adverse events of special interest, none of the patients reported Varicella Zoster reactivation and no case of MACE nor thromboembolic events were recorded.

Conclusion The rapid effect of tofacitinib in long standing RA patients allowed a significant reduction of the daily prednisone dose leading to the discontinuation of glucocorticoids in up to 30% of patients, without limiting the drug effectiveness.

Reference [1] Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 2023;82:3-18.

Acknowledgements: NIL.

Disclosure of Interests Francesca Romana Spinelli Speakers bureau: Amgen, Abbvie, Elil Lilly, Galapagos, Consultant of: Abbvie, Eli Lilly, Galapagos, Grant/research support from: Pfizer, cristina garufi Speakers bureau: Eli Lilly, Silvia Mancuso: None declared, fulvia ceccarelli: None declared, Simona Truglia: None declared, Fabrizio Conti Speakers bureau: Abbvie, BMS, Eli Lilly, Galapagos, Consultant of: Abbvie, BMS, Eli Lilly, Galapagos.

  • Targeted synthetic drugs
  • Clinical trials
  • Tapering

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