Psoriatic ArthritisPhase 3MUSTNCT03148860
Impact of Concomitant MTX on Efficacy, Safety and Adherence of Ustekinumab-treatment in Patients With Active PsA
A Phase 3 study testing Methotrexate and Ustekinumab in people with Psoriatic Arthritis, run by Dr. Frank Behrens at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Psoriatic Arthritis
- What is being tested?
- Methotrexate and Ustekinumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 186 participants
- Where
- 1 siteGermany
- Study dates
- 15 Dec 2016to 21 Oct 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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- Permitted pre-treatment with up to three biologic-agents, whereupon only one biologic agent must be withdrawn due to inadequate response.
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- 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
Who cannot join
- Exclusion criteria related to Investigational medicinal product (IMP):
- Previous use of UST or any other anti-IL23 agent
- according to SmPC
- Inadequate Response to prior MTX-treatment for Psoriatic Arthritis
- previous B-cell depleting therapy
- Patients with other chronic inflammatory articular disease or systemic autoimmune disease with musculoskeletal symptoms
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- Patients with active Tb
- Patients with latent Tb, measured by Interferon gamma release assay, that are not pre-treated for at least 1 months and planned to be treated 9 months in total with INH once a day according to local guidelines
- Any active infection, a history of recurrent clinically significant infection, a history of recurrent bacterial infections with encapsulated organisms
- Primary or secondary immunodeficiency
- History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised
- Evidence of significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and of the study outcome
- History of a severe psychological illness or condition
- Known hypersensitivity to any component of the product
- Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test
- Males or females of reproductive potential not willing to use effective contraception (e.g. contraceptive pill, IUD, physical barrier)
- Alcohol, drug or chemical abuse Exclusion criteria related to prior treatments
- Previous DMARD therapy other than MTX at least for the last 28 days prior screening due to washout time of different DMARD therapies (including Leflunomide etc.)
- Previous immunosuppressive biologic therapy at least for the last
- 4 weeks prior to screening for Enbrel® (etanercept) - with a terminal half-life of 102 ± 30 hours (s.c. route)
- 10 weeks prior to screening for Humira® (adalimumab) - with a terminal half-life of 10-20 days (average 2 weeks) (s.c. route)
- 10 weeks prior to screening for Simponi® (golimumab) - with a terminal half-life of 11-14 days
- 10 weeks prior to screening for Cimzia® (certolizumab) - with a terminal half-life of approx. 14 days
- 8 weeks prior to screening for Remicade® (infliximab) - with a terminal half-life of 8.0-9.5 days (i.v. infusion)
- 60 days prior to screening due to washout time of other immunosuppressive biologic therapies
- current participation in another interventional clinical trial
- Haemoglobin < 8.5 g / dl
- Neutrophil counts < 1.500 / μl
- Platelet count < 75.000 / μl
- Lower than 1 x 1000 / μl lymphopenia for more than three months prior to inclusion.
- Serum creatinine > 1.4 mg / dl for women or 1.6 mg / dl for men
- AST or ALT > 2.5 time upper limit of norm
- Underage or incapable patients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Concomitant Methotrexate on Efficacy, Safety and Adherence of Ustekinumab-treatment in Patients With Active Psoriasis Arthritis
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.
Read the 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.
- Conditions
- Psoriatic Arthritis
- Being tested
- Methotrexate, Ustekinumab, Placebo
- Keywords
- Psoriatic Arthritis, Ustekinumab, Methotrexate, DAS28
- Medical subject headings
- Arthritis, Psoriatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
subjects will receive once weekly 15 mg (3 capsules) MTX
UstekinumabDrug
Also called Stelara
subject will receive Ustekinumab open-label over a treatment period of 52 weeks
PlaceboOther
subjects will receive once weekly 3 capsules PLC to MTX
| Study group | Role | What they receive |
|---|---|---|
| Methotrexate naive - Ustekinumab and Methotrexate | Active comparator | Methotrexate naive subjects will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label Receives: Drug: Methotrexate; Drug: Ustekinumab |
| Methotrexate naive - Ustekinumab and Placebo to Methotrexate | Placebo comparator | Methotrexate naive subjects will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label Receives: Drug: Ustekinumab; Other: Placebo |
| Methotrexate pre-treated subjects-Ustekinumab and Methotrexate | Active comparator | subjects pretreated with Methotrexate will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label Receives: Drug: Methotrexate; Drug: Ustekinumab |
| Methotrexate pre-treated subjects-Ustekinumab and PLC | Placebo comparator | subjects pretreated with Methotrexate will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label Receives: Drug: Ustekinumab; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of mean values of DAS28 at 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.
Measured: week 24
Secondary outcomes (68)
Assessment of mean DAS28 at 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.
Measured: week 52
Assessment of DAS28
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.
Measured: week 4
Assessment of DAS28
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.
Measured: week 16
Assessment of DAS28
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.
Measured: week 24
Assessment of DAS28
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.
Measured: week 40
Assessment of DAS28
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.
Measured: week 52
change in DAS28
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.
Measured: baseline to week 4
change in DAS28
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.
Measured: baseline to week 16
change in DAS28
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.
Measured: baseline to week 24
change in DAS28
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.
Measured: baseline to week 40
change in DAS28
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.
Measured: baseline to week 52
DAS28-ESR remission
Measured: week 4
DAS28-ESR remission
Measured: week 16
DAS28-ESR remission
Measured: week 24
DAS28-ESR remission
Measured: week 40
DAS28-ESR remission
Measured: week 52
Assessment of Tender joint count/Swollen joint count (TJC/SJC) (68/66)
Tender and swollen joint will be assessed and counted by trained personel
Measured: week 4
Assessment of TJC/SJC (68/66)
Tender and swollen joint will be assessed and counted by trained personel
Measured: week 16
Assessment of TJC/SJC (68/66)
Tender and swollen joint will be assessed and counted by trained personel
Measured: week 24
Assessment of TJC/SJC (68/66)
Tender and swollen joint will be assessed and counted by trained personel
Measured: week 40
Assessment of TJC/SJC (68/66)
Tender and swollen joint will be assessed and counted by trained personel
Measured: week 52
ACR (20/50/70) response
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
Measured: week 4
ACR (20/50/70) response
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
Measured: week 16
ACR (20/50/70) response
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
Measured: week 24
ACR (20/50/70) response
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
Measured: week 40
ACR (20/50/70) response
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
Measured: week 52
Change in ACR core set
Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described
Measured: baseline to week 4
Change in ACR core set
Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described
Measured: baseline to week 16
Change in ACR core set
Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described
Measured: baseline to week 24
Change in ACR core set
Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described
Measured: baseline to week 40
Change in ACR core set
Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described
Measured: baseline to week 52
Assessment of PASI
The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients
Measured: week 4
Assessment of BASDAI
The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement
Measured: week 4
Assessment of BSA
The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients.
Measured: week 4
Assessment of BASDAI
The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement
Measured: week 16
Assessment of PASI
The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients
Measured: week 16
Assessment of BSA
The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients.
Measured: week 16
Assessment of BASDAI
The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement
Measured: week 24
Assessment of PASI
The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients
Measured: week 24
Assessment of BSA
The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients.
Measured: week 24
Assessment of PASI
The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients
Measured: week 40
Assessment of BSA
The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients.
Measured: week 40
Assessment of BASDAI
The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement
Measured: week 40
Assessment of PASI
The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients
Measured: week 52
Assessment of BSA
The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients.
Measured: week 52
Assessment of BASDAI
The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement
Measured: week 52
Treatment adherence measured by patient diary
Compliance with treatment will be determined by patient diary
Measured: through treatment period; normally 52 weeks
Compliance measured by questionnaire CQR5
The CQR5 consists of 5 questions addressing information on treatment compliance of the patient.
Measured: through treatment period; normally 52 weeks
Quality of life measured by HAQ
Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA
Measured: week 4
Quality of life measured by EQ5D
EQ5D is a standardised instrument for use as a measure of health outcome
Measured: week 4
Quality of life measured by DLQI
The Dermatology Life Quality Index is a 10-question validated questionnaire.
Measured: week 4
Quality of life measured by EQ5D
EQ5D is a standardised instrument for use as a measure of health outcome
Measured: week 16
Quality of life measured by HAQ
Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA
Measured: week 16
Quality of life measured by DLQI
The Dermatology Life Quality Index is a 10-question validated questionnaire.
Measured: week 16
Quality of life measured by DLQI
The Dermatology Life Quality Index is a 10-question validated questionnaire.
Measured: week 24
Quality of life measured by EQ5D
EQ5D is a standardised instrument for use as a measure of health outcome
Measured: week 24
Quality of life measured by HAQ,
Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA
Measured: week 24
Quality of life measured by HAQ
Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA
Measured: week 40
Quality of life measured by EQ5D
EQ5D is a standardised instrument for use as a measure of health outcome
Measured: week 40
Quality of life measured by DLQI
The Dermatology Life Quality Index is a 10-question validated questionnaire.
Measured: week 40
Quality of life measured by HAQ
Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA
Measured: week 52
Quality of life measured by EQ5D
EQ5D is a standardised instrument for use as a measure of health outcome
Measured: week 52
Quality of life measured by DLQI
The Dermatology Life Quality Index is a 10-question validated questionnaire.
Measured: week 52
Assessment of Change in Dactylitis
Functional assessment: Change in number and severity of digits involved) involved
Measured: week 4, 16, 24, 40 and week 52
Assessment of Change in Enthesitis (LEI)
functional outcome
Measured: week 4, 16, 24, 40 and week 52
Assessment of mtNAPSI
The modified target Nail Psoriasis Severity Index is used for evaluation of nail involvement in patients
Measured: week 4, 16, 24, 40 and week 52
Ultrasound (US) assessment of joints and enthesis according to PASON22
selected sites only
Measured: Week 4, 24 and week 52
Frequency and seriousness of adverse events as reported and documented in Case report form
Documentation of the occurence, frequency and seriousness of adverse events as reported and documented in Case report form
Measured: each study visit (week 0 to week 52)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2017
- Study start15 Dec 2016
- Primary completion12 Apr 2021
- Study completion21 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Psoriatic ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomised, placebo-controlled, double-blind, multicenter study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 186 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Frank Behrens
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen-Cilag Ltd.
- Responsible party
- Sponsor-investigator, Dr. Frank Behrens, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
- Investigators
- Frank Behrens, MD, Principal investigator, Fraunhofer IME
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03148860
- Sponsor's protocol ID
- TMP-1115_01
- Acronym
- MUST
- Status last verified
- Mar 2022
- First submitted
- 4 Apr 2017
- Last updated
- 2 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Koehm M, Rossmanith T, Foldenauer AC, Herrmann E, Brandt-Jurgens J, Burmester GR, Kellner H, Kiltz U, Kofler DM, Rech J, Mojtahed-Poor S, Jonetzko C, Burkhardt H, Behrens F; MUST Investigator Group. Methotrexate plus ustekinumab versus ustekinumab monotherapy in patients with active psoriatic arthritis (MUST): a randomised, multicentre, placebo-controlled, phase 3b, non-inferiority trial. Lancet Rheumatol. 2023 Jan;5(1):e14-e23. doi: 10.1016/S2665-9913(22)00329-0.
PubMed 38251504Mojtahed Poor S, Henke M, Ulshofer T, Kohm M, Behrens F, Burkhardt H, Schiffmann S. The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate. Rheumatology (Oxford). 2023 Dec 1;62(12):3993-3999. doi: 10.1093/rheumatology/kead177.
PubMed 37079726
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Concomitant Methotrexate on Efficacy, Safety and Adherence of Ustekinumab-treatment in Patients With Active Psoriasis Arthritis
- ClinicalTrials.gov ID
- NCT03148860
- Acronym / sponsor ID
- MUST / TMP-1115_01
- Conditions
- Psoriatic Arthritis
- Keywords
- Psoriatic Arthritis, Ustekinumab, Methotrexate, DAS28
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 186 participants (actual)
- Lead sponsor
- Dr. Frank BehrensUniversity, hospital or other
- Collaborators
- Janssen-Cilag Ltd.
- Study start
- 15 Dec 2016 (actual)
- Primary completion
- 12 Apr 2021 (actual)
- Study completion
- 21 Oct 2021 (actual)
- First posted
- 11 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- randomised, placebo-controlled, double-blind, multicenter study
| Arm | Type | Receives |
|---|---|---|
| Methotrexate naive - Ustekinumab and Methotrexate | Active comparator | Drug: Methotrexate, Drug: UstekinumabMethotrexate naive subjects will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label |
| Methotrexate naive - Ustekinumab and Placebo to Methotrexate | Placebo comparator | Drug: Ustekinumab, Other: PlaceboMethotrexate naive subjects will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label |
| Methotrexate pre-treated subjects-Ustekinumab and Methotrexate | Active comparator | Drug: Methotrexate, Drug: Ustekinumabsubjects pretreated with Methotrexate will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label |
| Methotrexate pre-treated subjects-Ustekinumab and PLC | Placebo comparator | Drug: Ustekinumab, Other: Placebosubjects pretreated with Methotrexate will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (33 listed)
- Previous use of UST or any other anti-IL23 agent
- according to SmPC
- Inadequate Response to prior MTX-treatment for Psoriatic Arthritis
- previous B-cell depleting therapy
- Patients with other chronic inflammatory articular disease or systemic autoimmune disease with musculoskeletal symptoms
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methotrexatesubjects will receive once weekly 15 mg (3 capsules) MTX | Drug | Methotrexate naive - Ustekinumab and Methotrexate, Methotrexate pre-treated subjects-Ustekinumab and Methotrexate |
| UstekinumabAlso: Stelarasubject will receive Ustekinumab open-label over a treatment period of 52 weeks | Drug | Methotrexate naive - Ustekinumab and Methotrexate, Methotrexate naive - Ustekinumab and Placebo to Methotrexate, Methotrexate pre-treated subjects-Ustekinumab and Methotrexate, Methotrexate pre-treated subjects-Ustekinumab and PLC |
| Placebosubjects will receive once weekly 3 capsules PLC to MTX | Other | Methotrexate naive - Ustekinumab and Placebo to Methotrexate, Methotrexate pre-treated subjects-Ustekinumab and PLC |
Primary outcome
Assessment of mean values of DAS28 at week 24
Time frame: 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.
68 secondary outcomes
Assessment of mean DAS28 at week 52
Time frame: week 52
Assessment of DAS28
Time frame: week 4
Assessment of DAS28
Time frame: week 16
Assessment of DAS28
Time frame: week 24
Assessment of DAS28
Time frame: week 40
Assessment of DAS28
Time frame: week 52
change in DAS28
Time frame: baseline to week 4
change in DAS28
Time frame: baseline to week 16
change in DAS28
Time frame: baseline to week 24
change in DAS28
Time frame: baseline to week 40
change in DAS28
Time frame: baseline to week 52
DAS28-ESR remission
Time frame: week 4
DAS28-ESR remission
Time frame: week 16
DAS28-ESR remission
Time frame: week 24
DAS28-ESR remission
Time frame: week 40
DAS28-ESR remission
Time frame: week 52
Assessment of Tender joint count/Swollen joint count (TJC/SJC) (68/66)
Time frame: week 4
Assessment of TJC/SJC (68/66)
Time frame: week 16
Assessment of TJC/SJC (68/66)
Time frame: week 24
Assessment of TJC/SJC (68/66)
Time frame: week 40
Assessment of TJC/SJC (68/66)
Time frame: week 52
ACR (20/50/70) response
Time frame: week 4
ACR (20/50/70) response
Time frame: week 16
ACR (20/50/70) response
Time frame: week 24
ACR (20/50/70) response
Time frame: week 40
ACR (20/50/70) response
Time frame: week 52
Change in ACR core set
Time frame: baseline to week 4
Change in ACR core set
Time frame: baseline to week 16
Change in ACR core set
Time frame: baseline to week 24
Change in ACR core set
Time frame: baseline to week 40
Change in ACR core set
Time frame: baseline to week 52
Assessment of PASI
Time frame: week 4
Assessment of BASDAI
Time frame: week 4
Assessment of BSA
Time frame: week 4
Assessment of BASDAI
Time frame: week 16
Assessment of PASI
Time frame: week 16
Assessment of BSA
Time frame: week 16
Assessment of BASDAI
Time frame: week 24
Assessment of PASI
Time frame: week 24
Assessment of BSA
Time frame: week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
- Derived from this study: PubMed 38251504Koehm M, Rossmanith T, Foldenauer AC, Herrmann E, Brandt-Jurgens J, Burmester GR, Kellner H, Kiltz U, Kofler DM, Rech J, Mojtahed-Poor S, Jonetzko C, Burkhardt H, Behrens F; MUST Investigator Group. Methotrexate plus ustekinumab versus ustekinumab monotherapy in patients with active psoriatic arthritis (MUST): a randomised, multicentre, placebo-controlled, phase 3b, non-inferiority trial. Lancet Rheumatol. 2023 Jan;5(1):e14-e23. doi: 10.1016/S2665-9913(22)00329-0.
- Derived from this study: PubMed 37079726Mojtahed Poor S, Henke M, Ulshofer T, Kohm M, Behrens F, Burkhardt H, Schiffmann S. The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate. Rheumatology (Oxford). 2023 Dec 1;62(12):3993-3999. doi: 10.1093/rheumatology/kead177.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Behrens, MD principal investigator
Fraunhofer IME
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methotrexate and Ustekinumab in people with Psoriatic Arthritis, run by Dr. Frank Behrens at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of mean values of DAS28 at week 24 (time frame: week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03148860, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.