Psoriatic Arthritis
Conditions
Keywords
Psoriatic arthritis, dactylitis, enthesitis
Brief summary
Dactylitis is a poor prognostic factor in psoriatic arthritis (PsA) patients. The efficacy of synthetic or biologic disease modifying anti-rheumatic drugs (DMARDs) on dactylitis has not been previously studied in randomized controlled trials as a primary endpoint. In this investigator initiated clinical trial the investigators aim to test the hypothesis that the combination therapy of golimumab and methotrexate (MTX) will result in a significant improvement of dactylitis in comparison with MTX monotherapy, in MTX naïve psoriatic arthritis patients, at week 24. Similarly the efficacy on enthesitis, peripheral and axial involvement, skin and nail psoriasis, inflammation and damage of the feet and hands assessed by magnetic resonance imaging (MRI), composite indexes of disease activity, remission, function and quality of life will be determined. This is a national multicentre, interventional, double-blinded, placebo-controlled, parallel design trial. 136 patients with active dactylitis, refractory to at least two systemic non-steroidal anti-inflammatory drugs (NSAIDs), at optimal dosage, for 3 months will be included and centrally randomized to golimumab in combination with MTX versus MTX monotherapy, in a 1:1 ratio. The study duration will be 24 weeks. The investigators expect the results from this trial will contribute to a better definition of the treatment algorithm of PsA patients with dactylitis.
Interventions
DRUGGolimumab
Prefilled syringe with golimumab 50mg (Simponi®) administrated subcutaneously, once monthly, for 24 weeks.
DRUGMethotrexate
MTX started at 15mg/weekly at baseline, increased to 20mg/weekly at week 4 and to 25mg/weekly at week 8, maintaining the dose of 25mg/weekly throughout the trial period of 24 weeks, except in case of intolerance or toxicity
DRUGPlacebo
The prefilled syringe with placebo will be administrated subcutaneously, once monthly, for 24 weeks.
Sponsors
Merck Sharp & Dohme LLC
Instituto de Medicina Molecular João Lobo Antunes
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each subject must be/have….. * Able and willing to give written informed consent and comply with the requirements of the study protocol. * Age ≥ 18 years old, at baseline. A subject may be of both gender and any race/ethnicity. * PsA diagnosis according to Classification of Psoriatic Arthritis (CASPAR) criteria, established at least 3 months prior to screening. * Active psoriatic arthritis, at the time of entry into the study, defined by: ≥1 tender dactylitis, refractory to at least two systemic NSAIDs, at optimal dosage, for 3 months and at least one other site of active inflammation (peripheral joints, enthesis, spine, skin or nails). * Naïve to MTX therapy. * Patients can have been previously treated with synthetic DMARDs (except MTX) or corticosteroids but must have withdrawn according to the following schedules: * All synthetic DMARDs and oral corticosteroids withdrawn at least two weeks prior to screening or 5 half lives according, to what is longer, except for leflunomide. * leflunomide ≥ 12 weeks or ≥ 2 weeks after standard cholestyramine or activated charcoal washout. * Up to a maximum of two local corticosteroids injection are allowed, administrated, at least four weeks prior to screening (indication for local corticoids injection is dependent on expert opinion decision). * NSAIDs (up to the maximum recommend dose) if the dose has been stable for at least 4 weeks prior to baseline and the patient is expected to remain on the baseline dose for the 6 months of the study. * Female subjects or male subjects and his female sexual partner of childbearing potential must agree to use a medically accepted method of contraception prior to enrollment, while receiving protocol-specified medication and for 6 months after stopping the medication. * Medically accepted methods of contraception include condoms (male or female) with a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), inert or copper containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation). Other methods may be used as required by local legislation. * Postmenopausal women are not required to use contraception (postmenopausal is defined as at least 12 consecutive months without a spontaneous menses).
Exclusion criteria
A subject meeting any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dactylitis Severity Score (DSS) | From baseline to week 24 | Changes from baseline in Dactylitis Severity Score at 24 weeks. Each digit with dactylitis was evaluated in a severity scale from 0 to 3 (0 = no dactylitis; 1 = mild dactylitis, 2 = moderate dactylitis, 3 = severe dactylitis). The total score is calculated as the sum of the individual digits dactylitis scores, ranging from a minimum 0 to a maximum of 60, with higher scores corresponding to worse severities. |
Countries
Portugal
Participant flow
Recruitment details
GO-DACT was a proof-of-concept multicentric, investigator-initiated trial conducted between August 2014 and June 2017, in 13 Rheumatology centres in Portugal.
Participants by arm
| Arm | Count |
|---|---|
| Golimumab in Combination With Methotrexate Golimumab 50mg, subcutaneous, once monthly, for 24 weeks, in combination with MTX.
MTX started at 15mg/weekly at baseline, increased to 20mg/weekly at week 4 and to 25mg/weekly at week 8, maintaining the dose of 25mg/weekly throughout the trial period of 24 weeks, except in case of intolerance or toxicity
Golimumab: Prefilled syringe with golimumab 50mg (Simponi®) administrated subcutaneously, once monthly, for 24 weeks.
Methotrexate: MTX started at 15mg/weekly at baseline, increased to 20mg/weekly at week 4 and to 25mg/weekly at week 8, maintaining the dose of 25mg/weekly throughout the trial period of 24 weeks, except in case of intolerance or toxicity | 21 |
| Placebo in Combination With Methotrexate MTX started at 15mg/weekly at baseline, increased to 20mg/weekly at week 4 and to 25mg/weekly at week 8, maintaining the dose of 25mg/weekly throughout the trial period of 24 weeks, except in case of intolerance or toxicity.
Methotrexate: MTX started at 15mg/weekly at baseline, increased to 20mg/weekly at week 4 and to 25mg/weekly at week 8, maintaining the dose of 25mg/weekly throughout the trial period of 24 weeks, except in case of intolerance or toxicity
Placebo: The prefilled syringe with placebo will be administrated subcutaneously, once monthly, for 24 weeks. | 23 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 0 |
Baseline characteristics
| Characteristic | Golimumab in Combination With Methotrexate | Placebo in Combination With Methotrexate | Total |
|---|---|---|---|
| Age, Continuous | 46.2 years | 44.1 years | 45.7 years |
| Dactylitis Severity Score (DSS) | 6.0 score on a scale | 6.0 score on a scale | 6.0 score on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 22 Participants | 42 Participants |
| Region of Enrollment Portugal | 21 participants | 23 participants | 44 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 17 Participants | 20 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 21 |
| other Total, other adverse events | 14 / 23 | 17 / 21 |
| serious Total, serious adverse events | 1 / 23 | 0 / 21 |
Outcome results
Primary
Dactylitis Severity Score (DSS)
Changes from baseline in Dactylitis Severity Score at 24 weeks. Each digit with dactylitis was evaluated in a severity scale from 0 to 3 (0 = no dactylitis; 1 = mild dactylitis, 2 = moderate dactylitis, 3 = severe dactylitis). The total score is calculated as the sum of the individual digits dactylitis scores, ranging from a minimum 0 to a maximum of 60, with higher scores corresponding to worse severities.
Time frame: From baseline to week 24
Population: An intention-to-treat analysis (ITT) was performed for the primary endpoint, applying the last observation carried forward method and including all randomly assigned patients who received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo in Combination With Methotrexate | Dactylitis Severity Score (DSS) | -2 change of score on a scale |
| Golimumab in Combination With Methotrexate | Dactylitis Severity Score (DSS) | -5 change of score on a scale |
p-value: =0.026Wilcoxon (Mann-Whitney)