Induction and Tapering Therapy With Tofacitinib and Glucocorticoid in Patients With Polymyalgia Rheumatica

Phase 3

Recruiting

• Conditions: Polymyalgia Rheumatica
• Interventions: Drug: Prednisone+Tofacitinib; Drug: Prednisone

• Registration Number: NCT06172361
• Lead Sponsor: Zhejiang University

Brief Summary

This will be efficacy and safety of Induction and Tapering Therapy with Tofacitinib and Glucocorticoid in patients with Polymyalgia Rheumatica (ITTG PMR): An open-label 52-week randomized controlled trial

Detailed Description

Rheumatic polymyalgia (PMR) is more commonly observed in individuals over the age of 50, who may have a higher prevalence of osteoporosis, diabetes, cardiovascular diseases, and other chronic conditions. Currently, glucocorticoids are the primary treatment for PMR, but they can lead to various side effects, and recurrence is common during steroid tapering. Our previous 24-week study confirmed the effective treatment of PMR patients with tofacitinib. Given the relatively slow efficacy of tofacitinib, early adjunctive therapy with NSAIDs is needed. To address this, we are planning an open-label 52-week randomized controlled trial. This study aims to assess the use of tofacitinib in combination with glucocorticoids to induce rapid improvement, followed by rapid tapering of steroids and slow tapering of tofacitinib. The objective is to observe the efficacy and safety of this regimen for PMR, providing a new treatment option for clinical use.

Study Timeline

• Study First Submitted: 2023-12-07
• Study First Submitted QC: 2023-12-07
• Study First Posted: 2023-12-15
• Study Start: 2024-01-20
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-25
• Last Update Posted: 2024-07-29
• Primary Completion: 2025-09-30
• Study Completion: 2026-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

1. PMR patients who fulfilled the 1982 Chuang criteria or 2012ACR/EULAR criteria for PMR; They did not receive any glucocorticoids or biological agents during the 2 weeks period that preceded their inclusion in the study;
2. Patients with high activity rheumatic polymyalgia: disease activity score PMR-AS (Table 3) > 10,
3. Adults age 50-88, Weight 45-85Kg,
4. ESR>20mm/h or CRP >50mg/L (5mg/dl),
5. Informed consent.

Exclusion Criteria

1. Patients with known allergies to tofacitinib, prednisone or methylprednisolone,
2. Patients with identified giant cell arteritis, systemic lupus erythematosus, rheumatoid arthritis, calcium pyrophosphate deposition (CPPD) arthropathy, and other rheumatic diseases,
3. Patients with severe osteoarthritis,
4. Subjects with any severe acute, chronic or recurrent infection (e.g. pneumonia or pyelonephritis, recurrent pneumonia, chronic bronchiectasis, tuberculosis, etc.),
5. Hepatitis B virus carriers or individuals with chronic active hepatitis B or C, other chronic liver diseases, HIV infection,
6. Patients with abnormal liver function (ALT/AST 2 times higher); Moderate to severe renal impairment (glomerular filtration rate <60); hyperlipidemia not improved by lipid-lowering drugs,
7. Pregnant or lactating women,
8. Patients with a history of malignancy who do not meet the following condition (patients with malignant tumors who have been successfully treated for more than 5 years before screening without any evidence of recurrence),
9. Patients with previous visual field disorder or single eye dysfunction, cataract patients,
10. Patients with decompensated cardiac insufficiency or severe hypertension or diabetes mellitus, i.e. systolic blood pressure higher than 160mmhg or diastolic blood pressure higher than 100mmhg,
11. For patients with abnormal blood routine, lymphocytes <500/mm3 or ANC <1000/mm3 or HGB < 90g/L,
12. Patients with active bleeding and peptic ulcer,
13. Have used biological agents or added azathioprine, leflunomide, FK 506 within 1 month before enrollment,
14. Those who have participated in other drug clinical trials within 4 weeks,
15. Patients using CYP3A4 inhibitors or inducers such as ketoconazole, fluconazole, or rifampicin within 4 weeks.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment group	Prednisone+Tofacitinib	Prednisone (or equivalent dose of methylprednisolone) + Tofacitinib
Positive control group	Prednisone	prednisone (or equivalent dose of methylprednisolone)

Primary Outcome Measures

Name	Time	Method
Proportion of patients with PMR-AS score <10 score at weeks 52	at 52 weeks	PMR-AS score: CRP (mg/dL)+Patient self-evaluation (0-10 visual scale)+ Physician global assessment (0-10 Visual Scale)+\[morning stiffness (min) x0.1\]+ EUL (0-3)

Secondary Outcome Measures

Name	Time	Method
ESR at weeks 24	at 24 weeks	ESR (mm/h)
PMR-AS score at weeks 24	at 24 weeks	PMR-AS score: CRP (mg/dL)+Patient self-evaluation (0-10 visual scale)+ Physician global assessment (0-10 Visual Scale)+\[morning stiffness (min) x0.1\]+ ability to elevate the upper limbs(EUL 0-3)
CRP at weeks 24	at 24 weeks	CRP (mg/dL)
CRP at weeks 52	at 52 weeks	CRP (mg/dL)
Proportion of patients who discontinue drugs at weeks 52	at 52 weeks	Proportion of patients who discontinue Tof in the treatment group, prednisone in the control group at weeks 52
PMR-AS score at weeks 52	at 52 weeks	PMR-AS score: CRP (mg/dL)+Patient self-evaluation (0-10 visual scale)+ Physician global assessment (0-10 Visual Scale)+\[morning stiffness (min) x0.1\]+EUL (0-3)
ESR at weeks 52	at 52 weeks	ESR (mm/h)

Trial Locations

Locations (1)

Division of Rheumatology, the First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China