Psoriatic Arthritis
Conditions
Keywords
Psoriatic Arthritis, Ustekinumab, Methotrexate, DAS28
Brief summary
Methotrexate (MTX) co-medication can improve the therapeutic effect of biological therapies (e.g. Tumor necrosis factor (TNF) -inhibitors) in rheumatoid arthritis (RA), but its role in Psoriatic Arthritis (PsA) remains unclear. No data from Randomized Clinical Trials (RCTs) are available to address the questions whether add-on of MTX to UST monotherapy, or a withdrawal of continuous MTX therapy in patients with newly initiated Ustekinumab (UST) treatment or simultaneously induction of MTX with UST in naive active PsA-patients will influence outcome measurements. So, the purpose of the study is to analyse the effects of blinded MTX-co-medication on outcome in patients treated with UST: Non-inferiority at week 24 of UST monotherapy compared to add-on to MTX in patients with active PsA and at least 12 weeks of MTX treatment prior to screening or who are actually not treated with MTX and do not have prior inadequate response to MTX-treatment for PsA will be demonstrated.
Detailed description
Methotrexate (MTX) co-medication can improve the therapeutic effect of biological therapies (e.g. TNF-inhibitors) in rheumatoid arthritis (RA), but its role in Psoriatic Arthritis (PsA) remains unclear. Differences in phenotypical manifestations between PsA and RA might influence the impact of co-medication, treatment response and treatment adherence differently. Independent from this data, the impact of use of MTX in Ustekinumab (UST) treated patients with active PsA remains unclear: No data from Randomized Clinical Trials (RCTs) are available to address the questions whether add-on of MTX to UST monotherapy, or the other way around, a withdrawal of continuous MTX therapy in patients with newly initiated UST treatment or simultaneously induction of MTX with UST in patients will influence outcome. There is some evidence that MTX may contribute to improved treatment persistence with anti-TNF therapy, particularly when used in combination with infliximab, but there is very little data to support a benefit in effectiveness in patients receiving concomitant MTX. Additionally, MTX may play a role in immunogenicity: In the PSUMMIT program the patients with concomitant MTX had lower anti-drug-antibody (ADA) rates than those on UST-monotherapy, although there was no effect on efficacy and safety. Furthermore, methotrexate treatment manifestations such as dactylitis or enthesitis seems to be ineffective. In this study, the effect of blinded MTX-co-medication on outcome in patients treated with UST will be analysed. Differences on efficacy, safety and treatment adherence will be calculated related to MTX use in four arms of the stratified, randomized placebo-controlled clinical trial which contains a study treatment period of 52 weeks. The primary endpoint, differences in DAS28 in the treatment groups, will be measured at week 24.
Interventions
DRUGMethotrexate
subjects will receive once weekly 15 mg (3 capsules) MTX
DRUGUstekinumab
subject will receive Ustekinumab open-label over a treatment period of 52 weeks
OTHERPlacebo
subjects will receive once weekly 3 capsules PLC to MTX
Sponsors
Janssen-Cilag Ltd.
Dr. Frank Behrens
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Methotrexate tablets will be encapsulated equal to Placebo to ensure blinding. Ustekinumab will be open-label
Intervention model description
randomised, placebo-controlled, double-blind, multicenter study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with active psoriatic arthritis who are naïve to UST will be stratified to either without MTX-therapy or on MTX-treatment (dosage 15mg once weekly) for at least 12 weeks prior to screening. * Active PsA is defined as TJC ≥4 and SJC ≥4 (68/66 joint count) and DAS28 ≥ 3,2 at screening * PsA according to CASPAR criteria * At least age of 18 years * Presence of chest x-ray without signs of active or latent infection (esp. for tuberculosis) within the last 3 months * Permitted pre-treatment with up to three biologic-agents, whereupon only one biologic agent must be withdrawn due to inadequate response. * For MTX-naive patients: Previous use of NSAID * Written informed consent obtained prior to the initiation of any protocol-required procedures * Compliance to study procedures and study protocol Inclusion criteria related to MTX * For the group on MTX: Patients must have stable MTX dosages of at least 15mg once weekly for at least 12 weeks prior to screening and stable MTX dosages of at 15mg once weekly for at least 4 weeks prior to screening * Compliance of intake of MTX must be documented by treating physician * For the group without MTX therapy: patients must be eligible for MTX treatment (according to SmPC) and have not failed prior MTX treatment for the treatment of PsA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of mean values of DAS28 at week 24 | week 24 | To demonstrate non-inferiority of mean values of DAS28 at week 24 of UST monotherapy compared to add-on to MTX with stratification according to patients on or without MTX before randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of mean DAS28 at week 52 | week 52 | The Disease Activity Score (DAS) consists of SJC and TJC measurements, the erythrocyte sedimentation rate (or CRP) and the subject's global assessment of disease activity. |
| change in DAS28 | baseline to week 4 | The Disease Activity Score (DAS) consists of SJC and TJC measurements, the erythrocyte sedimentation rate (or CRP) and the subject's global assessment of disease activity. |
| DAS28-ESR remission | week 4 | — |
| Assessment of Tender joint count/Swollen joint count (TJC/SJC) (68/66) | week 4 | Tender and swollen joint will be assessed and counted by trained personel |
| Assessment of TJC/SJC (68/66) | week 16 | Tender and swollen joint will be assessed and counted by trained personel |
| ACR (20/50/70) response | week 4 | Portion of Patient that reach 20%, 50% or 70% improvement in ACR score consisting of SJC and TJC measurements, subject's assessment of pain, subject's global assessment of disease activity, physician's global assessment of disease activity, HAQ and measurements of erythrocyte sedimentation rate and CRP |
| Change in ACR core set | baseline to week 4 | Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described |
| Assessment of PASI | week 4 | The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients |
| Assessment of BASDAI | week 4 | The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement |
| Assessment of BSA | week 4 | The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients. |
| Assessment of DAS28 | week 4 | The Disease Activity Score (DAS) consists of SJC and TJC measurements, the erythrocyte sedimentation rate (or CRP) and the subject's global assessment of disease activity. |
| Compliance measured by questionnaire CQR5 | through treatment period; normally 52 weeks | The CQR5 consists of 5 questions addressing information on treatment compliance of the patient. |
| Quality of life measured by HAQ | week 4 | Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA |
| Quality of life measured by EQ5D | week 4 | EQ5D is a standardised instrument for use as a measure of health outcome |
| Quality of life measured by DLQI | week 4 | The Dermatology Life Quality Index is a 10-question validated questionnaire. |
| Quality of life measured by HAQ, | week 24 | Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA |
| Assessment of Change in Dactylitis | week 4, 16, 24, 40 and week 52 | Functional assessment: Change in number and severity of digits involved) involved |
| Assessment of Change in Enthesitis (LEI) | week 4, 16, 24, 40 and week 52 | functional outcome |
| Assessment of mtNAPSI | week 4, 16, 24, 40 and week 52 | The modified target Nail Psoriasis Severity Index is used for evaluation of nail involvement in patients |
| Ultrasound (US) assessment of joints and enthesis according to PASON22 | Week 4, 24 and week 52 | selected sites only |
| Frequency and seriousness of adverse events as reported and documented in Case report form | each study visit (week 0 to week 52) | Documentation of the occurence, frequency and seriousness of adverse events as reported and documented in Case report form |
| Treatment adherence measured by patient diary | through treatment period; normally 52 weeks | Compliance with treatment will be determined by patient diary |
Countries
Germany
Outcome results
None listed