Safety and Efficacy of Tofacitinib vs Methotrexate in the Treatment of Psoriatic Arthritis (PsOLSET-BD)

October 17, 2019 updated by: Dr. Prayush Sharma, Globe Pharmaceuticals Limited

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background:

Methotrexate, an anti-folate drug, is a widely accepted and commonly used DMARD for the treatment of PsA. Tofacitinib is a JAK inhibitor, and relatively new drug for this condition.

Aims:

To assess and compare safety and efficacy of Tofacitinib and Methotrexate in the treatment of PsA.

Methodology:

This open label, randomized, prospective study was conducted in Department of Rheumatology, BSMMU, Dhaka for 1½ years from September, 2017 to February, 2019. 61 patients, aged >18 years with the diagnosis of PsA for ≥3 months were randomized into two groups. 29 patients (Tofacitinib 5mg BD) and 32 patients (MTX from 15 mg/week to 25 mg/week over 1 month) were enrolled and followed-up at the end of 1, 3 and 6 months. Primary endpoint was ACR 20 response at the end of 3 months. Patients who achieved treatment target on the basis of DAPSA score at the end of 3 months were allowed to continue previuos treatment and assessed for safety and efficacy till 6 months. Patients not achieving treatment target in Tofacitinib group were put on Tofacitinib 10 mg BD and in MTX group were put on Tofacitinib 5 mg BD. These patients were followed-up for safety and efficacy at the end of 6 months. Secondary outcome measures were EULAR response, 66/68 joints SJC/TJC, VAS for pain, ESR, CRP, DAPSA, DAS28, PASI, PASI 75 response, MASES and HAQ-DI. Safety assessment was done on the basis of clinical history, examination and laboratory findings at each follow-up. Ethical clearance was obtained from IRB, BSMMU at the beginning. Statistical analysis was done using chi-square test, Fisher's exact test, paired sample t-test and independent sample t-test. Missing data were dealt with intention to treat (ITT) analysis.

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bangladesh
      • Dhaka, Bangladesh, 1205
        • Bangabandhu Sheikh Mujib Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patients more than 18 years
  2. Psoriatic arthritis > 3 months with peripheral involvement diagnosed on the basis of CASPAR criteria
  3. Unresponsive to more than 2 NSAIDs at maximum recommended doses for more than 4 weeks, i.e 2 weeks for each NASID

5. Patients with active disease 6. PsA with or without extra-articular features like enthesitis, dactylitis and nail changes

Exclusion Criteria:

  1. Systemic infections requiring hospital admission during the past 6 months
  2. A history of active infectious disorders (including active or latent tuberculosis), and/or a history of chronic or recurrent serious infective diseases, opportunistic infections
  3. Hemoglobin (Hb) < 9 g/dl
  4. White blood cell count < 3000, Neutrophil count < 1000, Platelet count < 100000
  5. Live vaccines within 3 months prior to the first dose
  6. Serum creatinine > upper limit of normal reference range
  7. GFR less than 50 mL/min
  8. Alanine aminotransaminase (ALT) more than 2 times of ULN
  9. Pregnant or breast feeding, females of child-bearing potential not using highly effective contraception
  10. New York Heart Association Class III and IV congestive heart failure
  11. 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
  12. Any lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Group A- Tofacitinib
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 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.
Other Names:
  • Tofacitinib
PLACEBO_COMPARATOR: Group B- Methotrexate
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
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.
Other Names:
  • Methotrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
American college of Rheumatology 20 (ACR 20) response
Time Frame: 3 months

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease activity score-28 joint-ESR score (DAS28-ESR)
Time Frame: 1, 3 and 6 months

Disease activity score for assessment of disease activity of rheumatoid arthritis. It is calculated using the following parameters:

  1. Tender joint count- 28 joints
  2. Swollen joint count- 28 joints
  3. Patient global assessment (range 1-10)
  4. Erythrocyte sedimentation rate in mm in 1st hour Greater score means poor prognosis.A score of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission.
1, 3 and 6 months
Disease activity index for psoriatic Arthritis (DAPSA)
Time Frame: 1, 3 and 6 months

The DAPSA score consists of five variables: tender and swollen joints (TJC68, SJC66), patient global assessment and patient pain assessment (each on a 10-cm visual analogue scale [VAS]), and CRP. The addition of these variables is the result.

Disease Activity: 0-4 Remission, 5-14 low, 15-28 moderate, >28 high Disease Activity
1, 3 and 6 months
Psoriasis Area and Severity Index (PASI)
Time Frame: 1, 3 and 6 months

PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease).

The body is divided into four sections (head (H) (10% of a person's skin); arms (A) (20%); trunk (T) (30%); legs (L) (40%)). Each of these areas is scored by itself, and then the four scores are combined into the final PASI. For each section, the percent of area of skin involved, is estimated and then transformed into a grade from 0 to 6:

  1. 0% of involved area
  2. < 10% of involved area
  3. 10-29% of involved area
  4. 30-49% of involved area
  5. 50-69% of involved area
  6. 70-89% of involved area
  7. 90-100% of involved area Within each area, the severity is estimated by three clinical signs: erythema, induration and desquamation.
1, 3 and 6 months
Maastricht Ankylosing Spondylitis Enthesitis Score
Time Frame: 1, 3 and 6 months

The Maastricht Ankylosing Spondylitis Enthesitis Score uses 13 most specific and sensitive sites. These include the bilateral first and seventh costochondral joints, the anterior and posterior superior iliac spines, the iliac crests, the fifth lumbar spinous process, and the proximal insertion of Achilles tendon.

Total score-13 Range: 0-13 Greater score implies greeater entheses involvement, and thus greater disease activity.
1, 3 and 6 months
Health Assessment Questionnaire- Disability Index
Time Frame: 1, 3 and 6 months

An assessment tool for chronic diseases. A questionnaire where a person indicates the amount of difficulty they have with: dressing and grooming, arising, eating, walking, hygiene, reaching, gripping and performing common daily activities.

Total score- 3 Range- 0-3 Higher scores indicates higher disability.
1, 3 and 6 months
EULAR response
Time Frame: 3 months
EULAR response according to predefined changes in DAS28-ESR scores
3 months
66/68 joints SJC/TJC
Time Frame: 1, 3 and 6 months
SJC- swollen joint count and TJC- tender joint count
1, 3 and 6 months
ESR
Time Frame: 1, 3 and 6 months
Erythrocyte sedimentation rate
1, 3 and 6 months
CRP
Time Frame: 1, 3 and 6 months
C-reactive protein
1, 3 and 6 months
PASI75 response
Time Frame: 3 and 6 months
75% improvement in PASI score
3 and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Globe Pharmaceuticals Limited

Investigators

  • Principal Investigator: Prayush Sharma, MD, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 15, 2017

Primary Completion (ACTUAL)

September 28, 2019

Study Completion (ACTUAL)

September 28, 2019

Study Registration Dates

First Submitted

November 2, 2018

First Submitted That Met QC Criteria

November 7, 2018

First Posted (ACTUAL)

November 9, 2018

Study Record Updates

Last Update Posted (ACTUAL)

October 21, 2019

Last Update Submitted That Met QC Criteria

October 17, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PsOLSET-BD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Psoriatic Arthritis

Clinical Trials on Group A- Tofacitinib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kosovo

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe