Tofacitinib as a GC Sparing Agent for Polymyalgia Rheumatica

NCT04799262 | Completed Phase 2

• 1 other identifier: GCs Sparing Regimen in PMR
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Glucocorticoids are the cornerstone treatment for polymyalgia rheumatica but induce adverse events. The efficacy of the candidate drug Tofacitinib has not yet been demonstrated in controlled studies. The aim of the study is to investigate the efficacy and safety of Tofacitinib as a glucocorticoid sparing agent in patients with polymyalgia rheumatica.

Conditions

Polymyalgia Rheumatica; Effect of Drug; Safety Issues

Outcome Measures

Primary Outcomes (1)

• Response to treatment

  Response to treatment is defined as the achievement of sustained low disease activity (PMR-AS\<7) with GC independence (≤2.5mg/d) for 4 weeks from week 20

  24 week

Secondary Outcomes (9)

• Time till GC-free low disease activity within 24w

  24 week

• Time till first relapse within 24w

  24 week

• Cumulative GC dose at 24w

  24 week

• Proportion of patients with sustained remission with GC independence for 4 weeks from week 20

  24 week

• Incidence of adverse events (AEs) and Serious AEs (SAEs)

  24 week

Study Arms (1)

Tofacitinib+Prednisone

EXPERIMENTAL

Tofacitinib was given at the dose of 10mg daily through the 24 weeks. Prednisone (or equivalent oral GCs) of 15 mg daily at baseline willed be tapered to 2.5 mg or less within 20 weeks. Unless specifically considered by patients and physicians, the GC will be tapered followed the predefined taper regimen depending on the response to treatment judged by PMR-AS. The PMR-AS will be determined every two weeks; if\<10 the GC daily dosage was decreased by 2.5mg; if\>17, the GC daily dosage was increased to the previous dosage; if 10≤PMR-AS≤17, the GC daily dosage was maintained at the previous stable dose.

Drug: Tofacitinib 5 MG

Interventions

Tofacitinib 5 MG DRUG

Oral tofacitinib at the dose of 5mg twice a day was given for 24 weeks. Prednisone (or equivalent oral GCs) of 15 mg daily at baseline willed be tapered to 2.5 mg or less within 20 weeks. Unless specifically considered by patients and physicians, the GC will be tapered followed the predefined taper regimen depending on the response to treatment judged by PMR-AS. The PMR-AS will be determined every two weeks; if\<10 the daily GC dosage was decreased by 2.5mg; if\>17, the GC daily dosage was increased to the previous dosage; if 10≤PMR-AS≤17, the GC daily dosage was maintained at the previous stable dose.

Also known as: Prednisone

Tofacitinib+Prednisone

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male between 50 and 85 years old.
• PMR according to the ACR/ EULAR 2012 PMR classification criteria.
• Patients must have erythrocyte sedimentation rate (ESR) ≥20 mm/hr and/or CRP ≥8 mg/L associated with highly active PMR (PMR-AS\>17) within 2 weeks prior to screening.
• Patient is willing and able to take prednisone of 15 mg/day at baseline.
• Signed written informed consent.

You may not qualify if:

• Presence of any other connective tissue disease, such as but not limited to giant-cell arteritis, systemic lupus erythematosus, systemic sclerosis, vasculitis, myositis, mixed connective tissue disease, and ankylosing spondylitis.
• Concurrent diagnosis of active fibromyalgia, rhabdomyolysis or neuropathic muscular diseases.
• Organ transplant recipient.
• Any prior (within the defined period below) or concurrent use of immunosuppressive therapies but not limited to any of the following: ① Any prior use of tumor necrosis factor inhibitors, anti-IL-6 agents or JAK inhibitor; ② Alkylating agents including cyclophosphamide within 6 months of baseline; ③ Cell-depletion agents (e.g. anti-CD20) without evidence of recovery of B cells to baseline level; ④ Abatacept within 8 weeks of baseline; ⑤ Any prior use of csDMARDs at unstable dose for less than 12 weeks before baseline, e.g. cyclosporine, azathioprine, mycophenolate mofetil, leflunomide, MTX; ⑥ Concurrent use of systemic GCs for conditions other than PMR.
• Evidence (as assessed by the investigators) of active infection, such as presence of hepatitis B surface antigen (HBsAg) or hepatitis C antibody in blood, human immunodeficiency virus (HIV) positivity.
• Patients with a history of active or recurrent herpes zoster.
• Patients who have had surgery within 4 weeks of screening or planned surgery during study.
• Malignancy within 5 years prior to screening, except for non-melanoma skin cancer.
• Pregnant or breastfeeding woman.
• Any medical condition that could interfere with the implementation or interpretation of the study or with the safety of the patient during the study.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Ren Ji Hospital

Shanghai, 201112, China

Location

Related Publications (1)

• Zhang L, Li J, Yin H, Chen D, Li Y, Gu L, Fu Y, Chen J, Chen Z, Yang S, Ye S, Li T, Lu L. Efficacy and safety of tofacitinib in patients with polymyalgia rheumatica: a phase 2 study. Ann Rheum Dis. 2023 May;82(5):722-724. doi: 10.1136/ard-2022-223562. Epub 2023 Jan 5. No abstract available.

  PMID: 36604153 DERIVED

MeSH Terms

Conditions

Polymyalgia Rheumatica

Interventions

tofacitinib; Prednisone

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Ting Li, MD

  RenJi Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Assessor and data analyst blindness. To avoid bias, physicians who assess disease activity will be blinded. Participants are required not to discuss their treatment regimen with physicians at each visit. The success of the blind method will be judged by requiring the assessors to determine the therapy of participants after each visit. When the database is locked, the statistician will carry on the data analysis in the hidden of therapy.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 16, 2021
• Study Start: January 1, 2021
• Primary Completion: March 16, 2022
• Study Completion: May 1, 2022
• Last Updated: September 15, 2022

Record last verified: 2022-05

Locations

CN (1)