Safety and Efficacy of Tofacitinib vs Methotrexate in the Treatment of Psoriatic Arthritis

NCT03736161 | Completed Phase 3 DMC

• 1 other identifier: PsOLSET-BD
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Title Safety and Efficacy of Tofacitinib vs Methotrexate in the treatment of Psoriatic Arthritis- An Open Label Randomized single center study Psoriatic arthritis is defined as an inflammatory arthropathy associated with skin psoriasis and usually negative for rheumatoid factor. Till date, many NSAIDs, corticosteroids, DMARDs have been used, but the safety and efficacy issues demands more researches. The prevalence of PsA worldwide is about 1%-2% and among patients with psoriasis ranges from 7% to 42%. The pathogenesis of PsA involves many cytokines. Tofacitinib is an oral Janus Kinase (JAK) inhibitor with immunomodulatory and anti-inflammatory mechanism. It binds to JAK and prevents the activation of the JAK-signal transducers and activators of transcription (STAT) signaling pathway which ultimately decreases the production of pro-inflammatory cytokines, and prevents both inflammatory response and the inflammation-induced damage. It has shown better efficacy in many diseases like Rheumatoid Arthritis, Axial spondyloarthropathies, Psoriasis, Psoriatic Arthritis, Alopecia areata, dry eye disease. This prospective, open label, randomized study will be conducted in inpatient and outpatient departments of Rheumatology, BSMMU, Dhaka, Bangladesh in 110 adult volunteers (\>18 years) of both genders diagnosed as psoriatic arthritis. Patients will be divided equally into two groups, Group A will be put on Tofacitinib 5 mg twice daily and Group B will be put on Methotrexate weekly in increasing dose with maximum dose of 25 mg weekly. Groups will be divided on the basis of randomization by random number table. Patients with inadequate response to highest dose of MTX or Tofacitinib 5 mg BD at the end of 3 months will be put on Tofacitinib 5 mg BD or Tofacitinib 10 mg BD respectively. The patients not eligible for therapy will not be included in the study. Patients will be followed up at 1, 3 and 6 months. Baseline characteristics will be monitored and recorded at 3 and 6 months. The clinical information of the study subjects will be recorded in a structured history, clinical examination and questionnaire. All subjects will be enrolled after having informed written consent. The participants will enjoy every right to participate or withdraw from the study at any point of time. Response to Tofacitinib will be expressed in mean, standard deviation and percentage. Ethical clearance will be taken from the Institutional Review Board (IRB) of BSMMU.

Conditions

Psoriatic Arthritis

Keywords

PsA

Outcome Measures

Primary Outcomes (1)

• American college of Rheumatology 20 (ACR 20) response

  This response criteria is achieved if there is 20% improvement in tender or swollen joint counts along with 20% improvement in three of the following five parameters: 1. Erythrocyte sedimentation rate in mm in 1st hour 2. Patient assessment in numerical scale of 10 (range: 0-10) 3. Physician assessment in numerical scale of 10 (range: 0-10) 4. Visual analog pain scale (range: 0-10) 5. Disability/functional questionnaire with maximum score of 3 (range: 0-3)

  3 months

Secondary Outcomes (10)

• Disease activity score-28 joint-ESR score (DAS28-ESR)

  1, 3 and 6 months

• Disease activity index for psoriatic Arthritis (DAPSA)

  1, 3 and 6 months

• Psoriasis Area and Severity Index (PASI)

  1, 3 and 6 months

• Maastricht Ankylosing Spondylitis Enthesitis Score

  1, 3 and 6 months

• Health Assessment Questionnaire- Disability Index

  1, 3 and 6 months

Study Arms (2)

Group A- Tofacitinib

EXPERIMENTAL

Tofacitinib 5mg twice daily orally. Patients with inadequate response to Tofacitinib 5 mg BD at the end of 3 months will be put on Tofacitinib 10 mg BD.

Drug: Group A- Tofacitinib

Group B- Methotrexate

PLACEBO COMPARATOR

Methotrexate in increasing dose starting from 15 mg weekly to a maximum dose of 25 mg weekly from the end of 1st month. Patients with inadequate response to highest dose of MTX at the end of 3 months will be put on Tofacitinib 5 mg BD.

Drug: Group B- Methotrexate

Interventions

Group A- Tofacitinib DRUG

Group A patients will receive Tofacitinib 5mg BD. Patients will be followed up at 1, 3 and 6 months. Patients with inadequate response to Tofacitinib 5 mg BD at the end of 3 months will be put on Tofacitinib 10 mg BD. Primary endpoint for efficacy will be determined by ACR 20 response.

Also known as: Tofacitinib

Group A- Tofacitinib

Group B- Methotrexate DRUG

Group B patients will receive Methotrexate in increasing dose weekly with maximum dose up to 25 mg/week. Patients will be followed up at 1, 3 and 6 months. Patients with inadequate response to highest dose of MTX at the end of 3 months will be put on Tofacitinib 5 mg BD. Primary endpoint for efficacy will be determined by ACR 20 response.

Also known as: Methotrexate

Group B- Methotrexate

Eligibility Criteria

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

You may qualify if:

• Male or female patients more than 18 years
• Psoriatic arthritis \> 3 months with peripheral involvement diagnosed on the basis of CASPAR criteria
• Unresponsive to more than 2 NSAIDs at maximum recommended doses for more than 4 weeks, i.e 2 weeks for each NASID
• \. Patients with active disease 6. PsA with or without extra-articular features like enthesitis, dactylitis and nail changes

You may not qualify if:

• Systemic infections requiring hospital admission during the past 6 months
• A history of active infectious disorders (including active or latent tuberculosis), and/or a history of chronic or recurrent serious infective diseases, opportunistic infections
• Hemoglobin (Hb) \< 9 g/dl
• White blood cell count \< 3000, Neutrophil count \< 1000, Platelet count \< 100000
• Live vaccines within 3 months prior to the first dose
• Serum creatinine \> upper limit of normal reference range
• GFR less than 50 mL/min
• Alanine aminotransaminase (ALT) more than 2 times of ULN
• Pregnant or breast feeding, females of child-bearing potential not using highly effective contraception
• New York Heart Association Class III and IV congestive heart failure
• Evidence or history of malignancy, with the exception of adequately treated or excised non-metastatic basal or squamous cell cancer of the skin or cervical carcinoma in situ
• Any lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease

Sponsors & Collaborators

• Globe Pharmaceuticals Limited: lead

Study Sites (1)

Bangabandhu Sheikh Mujib Medical University

Dhaka, 1205, Bangladesh

Location

Related Publications (34)

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Related Links

• Safety, efficacy and tolerability of oral tofacitinib in Japanese patients with psoriasis and psoriatic arthritis
• Modulation of innate and adaptive immune by Tofacitinib
• EULAr 2015 recommendations for the treatment of Psoriatic Arthritis
• Pfizer's poster and oral presentation at ACR conference

MeSH Terms

Conditions

Arthritis, Psoriatic

Interventions

tofacitinib; Methotrexate

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Prayush Sharma, MD

  Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Open label randomized trial

Study Record Dates

• First Submitted: November 2, 2018
• First Posted: November 9, 2018
• Study Start: September 15, 2017
• Primary Completion: September 28, 2019
• Study Completion: September 28, 2019
• Last Updated: October 21, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)