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

NCT ID: NCT06172361

Last Updated: 2025-08-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-20
• Study Completion Date: 2026-01-30

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.

Conditions

Polymyalgia Rheumatica

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment group

Prednisone (or equivalent dose of methylprednisolone) + Tofacitinib

Group Type: EXPERIMENTAL

Prednisone+Tofacitinib

Intervention Type: DRUG

Withdrawal of prednisone (or equivalent dose of methylprednisolone) within 4 weeks: 5mg tid for 2 weeks, 5mg bid for 1 week, 5mg qd for 1 week, then discontinue.

Take Tofacitinib 10mg/d for 3 months, then 7.5mg/d for 2 months, followed by 5mg qd for 2 months, then 5mg qod for 2 months, and finally 5mg every 3 days for 2 months, discontinue the Tofacitinib for 1 month. If there is a relapse during the dose reduction process, resume Tofacitinib at the original dosage.

Positive control group

prednisone (or equivalent dose of methylprednisolone)

Group Type: ACTIVE_COMPARATOR

Prednisone

Intervention Type: DRUG

Prednisone 15mg (or equivalent dose of methylprednisolone) was set as the initial treatment of PMR. When improvement was achieved, the dose of Prednisone was reduced to 10mg daily within 4-10 weeks; When remission was achieved, then taper Prednisone gradually by 2.5mg every 6-8 weeks. Once relapse occurred, the dose increased to the pre-relapse dose. If reducing pred dosage is difficult, Methotrexate (MTX) 10mg qw can be added after 24 weeks.

Interventions

Prednisone+Tofacitinib

Withdrawal of prednisone (or equivalent dose of methylprednisolone) within 4 weeks: 5mg tid for 2 weeks, 5mg bid for 1 week, 5mg qd for 1 week, then discontinue.

Take Tofacitinib 10mg/d for 3 months, then 7.5mg/d for 2 months, followed by 5mg qd for 2 months, then 5mg qod for 2 months, and finally 5mg every 3 days for 2 months, discontinue the Tofacitinib for 1 month. If there is a relapse during the dose reduction process, resume Tofacitinib at the original dosage.

Intervention Type: DRUG

Prednisone

Prednisone 15mg (or equivalent dose of methylprednisolone) was set as the initial treatment of PMR. When improvement was achieved, the dose of Prednisone was reduced to 10mg daily within 4-10 weeks; When remission was achieved, then taper Prednisone gradually by 2.5mg every 6-8 weeks. Once relapse occurred, the dose increased to the pre-relapse dose. If reducing pred dosage is difficult, Methotrexate (MTX) 10mg qw can be added after 24 weeks.

Intervention Type: DRUG

Other Intervention Names

Pred+Tof; Pred

Eligibility Criteria

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 88 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Weiqian Chen

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Weiqian Chen

Role: PRINCIPAL_INVESTIGATOR

Division of Rheumatology, the First Affiliated Hospital, Zhejiang University School of Medicine

Locations

Division of Rheumatology, the First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yanlin He

Role: CONTACT

yanlinriver@163.com

8617799855659

Facility Contacts

Weiqian Chen, Doctor

Role: primary

cwq678@zju.edu.cn

+8613989814907

References

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Reference Type: BACKGROUND

PMID: 36125471 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36604153 (View on PubMed)

Ma X, Yang F, Wu J, Xu B, Jiang M, Sun Y, Sun C, Yu Y, Xu D, Xiao L, Ren C, Chen C, Ye Z, Liang J, Lin J, Chen W. Efficacy and Safety of Tofacitinib in Patients with Polymyalgia Rheumatica (EAST PMR): An open-label randomized controlled trial. PLoS Med. 2023 Jun 29;20(6):e1004249. doi: 10.1371/journal.pmed.1004249. eCollection 2023 Jun.

Reference Type: BACKGROUND

PMID: 37384596 (View on PubMed)

Spinelli FR, Garufi C, Mancuso S, Ceccarelli F, Truglia S, Conti F. Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib. Sci Rep. 2023 Sep 20;13(1):15537. doi: 10.1038/s41598-023-42371-z.

Reference Type: BACKGROUND

PMID: 37730835 (View on PubMed)

Dejaco C, Kerschbaumer A, Aletaha D, Bond M, Hysa E, Camellino D, Ehlers L, Abril A, Appenzeller S, Cid MC, Dasgupta B, Duftner C, Grayson PC, Hellmich B, Hocevar A, Kermani TA, Matteson EL, Mollan SP, Neill L, Ponte C, Salvarani C, Sattui SE, Schmidt WA, Seo P, Smolen JS, Thiel J, Toro-Gutierrez CE, Whitlock M, Buttgereit F. Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica. Ann Rheum Dis. 2024 Jan 2;83(1):48-57. doi: 10.1136/ard-2022-223429.

Reference Type: BACKGROUND

PMID: 36828585 (View on PubMed)

Other Identifiers

IIT20230087C-X1

Identifier Type: -

Identifier Source: org_study_id