Clinical trial NCT06172361: Induction and Tapering Therapy With Tofacitinib and Glucocorticoid in Patients With Polymyalgia Rheumatica
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Polymyalgia Rheumatica
Keywords: Polymyalgia Rheumatica
Tofacitinib
Glucocorticoid
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2023-12-15
Enrollment: 98
Sex: ALL
Minimum age (years): 50
Maximum age (years): 88
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Treatment group: Prednisone (or equivalent dose of methylprednisolone) + Tofacitinib

Positive control group: prednisone (or equivalent dose of methylprednisolone)
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of patients with PMR-AS score <10 score at weeks 52
timeFrame: at 52 weeks
Secondary outcomes:
measure: PMR-AS score at weeks 24
timeFrame: at 24 weeks
measure: PMR-AS score at weeks 52
timeFrame: at 52 weeks
measure: CRP at weeks 24
timeFrame: at 24 weeks
measure: CRP at weeks 52
timeFrame: at 52 weeks
measure: ESR at weeks 24
timeFrame: at 24 weeks
measure: ESR at weeks 52
timeFrame: at 52 weeks
measure: Proportion of patients who discontinue drugs at weeks 52
timeFrame: at 52 weeks
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Division of Rheumatology, the First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Division of Rheumatology, the First Affiliated Hospital, Zhejiang University School of Medicine
name: Weiqian Chen
role: PRINCIPAL_INVESTIGATOR
References:
citation: Devauchelle-Pensec V, Carvajal-Alegria G, Dernis E, Richez C, Truchetet ME, Wendling D, Toussirot E, Perdriger A, Gottenberg JE, Felten R, Fautrel BJ, Chiche L, Hilliquin P, Le Henaff C, Dervieux B, Direz G, Chary-Valckenaere I, Cornec D, Guellec D, Marhadour T, Nowak E, Saraux A. Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial. JAMA. 2022 Sep 20;328(11):1053-1062. doi: 10.1001/jama.2022.15459.
citation: 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.
citation: 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.
citation: 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.
citation: 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.