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CompletedNCT03148860MUSTUpdated Mar 2, 2022

Impact of Concomitant MTX on Efficacy, Safety and Adherence of Ustekinumab-treatment in Patients With Active PsA

A Phase 3 interventional study of Methotrexate and Ustekinumab in Psoriatic Arthritis, sponsored by Dr. Frank Behrens. Completed at 1 site in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-03-02.

Sponsored by Dr. Frank Behrens · Phase 3, Interventional, and Treatment

From the registry’s dates

  • Registered 3 months after the study started (first participant enrolled Dec 2016, registered Apr 2017).
Phase
Phase 3
Study type
Interventional
Enrollment
186
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

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.

02

Conditions studied

  • Psoriatic Arthritis

Keywords

  • Psoriatic Arthritis
  • Ustekinumab
  • Methotrexate
  • DAS28
03

In context

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 186 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.

Browse Arthritis studies →

Lead sponsor

Dr. Frank Behrens is the lead sponsor of 7 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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

Exclusion Criteria:

Exclusion criteria related to Investigational medicinal product (IMP):

  • Previous use of UST or any other anti-IL23 agent
  • according to SmPC

Exclusion criteria for the group without MTX:

  • Inadequate Response to prior MTX-treatment for Psoriatic Arthritis

Exclusion criteria related to general health:

  • previous B-cell depleting therapy
  • Patients with other chronic inflammatory articular disease or systemic autoimmune disease with musculoskeletal symptoms
  • 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

Exclusion criteria related to laboratory:

  • 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

Exclusion criteria related to formal aspects:

  • Underage or incapable patients
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
186 participants (actual)

Study arms

  • Active comparator
    Methotrexate naive - Ustekinumab and Methotrexate

    Methotrexate naive subjects will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label

    Drug: Methotrexate · Drug: Ustekinumab

  • Placebo comparator
    Methotrexate naive - Ustekinumab and Placebo to Methotrexate

    Methotrexate naive subjects will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label

    Drug: Ustekinumab · Other: Placebo

  • Active comparator
    Methotrexate pre-treated subjects-Ustekinumab and Methotrexate

    subjects pretreated with Methotrexate will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label

    Drug: Methotrexate · Drug: Ustekinumab

  • Placebo comparator
    Methotrexate pre-treated subjects-Ustekinumab and PLC

    subjects pretreated with Methotrexate will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label

    Drug: Ustekinumab · Other: Placebo

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

    Also known as: Stelara

  • OtherPlacebo

    subjects will receive once weekly 3 capsules PLC to MTX

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: week 24

Secondary outcomes

  1. 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.

    Time frame: week 52

  2. 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.

    Time frame: week 4

  3. 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.

    Time frame: week 16

  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.

    Time frame: week 24

  5. 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.

    Time frame: week 40

  6. 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.

    Time frame: week 52

  7. 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.

    Time frame: baseline to week 4

  8. 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.

    Time frame: baseline to week 16

  9. 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.

    Time frame: baseline to week 24

  10. 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.

    Time frame: baseline to week 40

  11. 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.

    Time frame: baseline to week 52

  12. DAS28-ESR remission

    Time frame: week 4

  13. DAS28-ESR remission

    Time frame: week 16

  14. DAS28-ESR remission

    Time frame: week 24

  15. DAS28-ESR remission

    Time frame: week 40

  16. DAS28-ESR remission

    Time frame: week 52

  17. Assessment of Tender joint count/Swollen joint count (TJC/SJC) (68/66)

    Tender and swollen joint will be assessed and counted by trained personel

    Time frame: week 4

  18. Assessment of TJC/SJC (68/66)

    Tender and swollen joint will be assessed and counted by trained personel

    Time frame: week 16

  19. Assessment of TJC/SJC (68/66)

    Tender and swollen joint will be assessed and counted by trained personel

    Time frame: week 24

  20. Assessment of TJC/SJC (68/66)

    Tender and swollen joint will be assessed and counted by trained personel

    Time frame: week 40

  21. Assessment of TJC/SJC (68/66)

    Tender and swollen joint will be assessed and counted by trained personel

    Time frame: week 52

  22. 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

    Time frame: week 4

  23. 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

    Time frame: week 16

  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

    Time frame: week 24

  25. 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

    Time frame: week 40

  26. 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

    Time frame: week 52

  27. Change in ACR core set

    Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described

    Time frame: baseline to week 4

  28. Change in ACR core set

    Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described

    Time frame: baseline to week 16

  29. Change in ACR core set

    Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described

    Time frame: baseline to week 24

  30. Change in ACR core set

    Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described

    Time frame: baseline to week 40

  31. Change in ACR core set

    Changes in SJC, TJC, HAQ, patient's and physician's global assessment, pain, CRP and ESR will be described

    Time frame: baseline to week 52

  32. 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

    Time frame: week 4

  33. Assessment of BASDAI

    The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement

    Time frame: week 4

  34. Assessment of BSA

    The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients.

    Time frame: week 4

  35. Assessment of BASDAI

    The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement

    Time frame: week 16

  36. 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

    Time frame: week 16

  37. Assessment of BSA

    The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients.

    Time frame: week 16

  38. Assessment of BASDAI

    The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement

    Time frame: week 24

  39. 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

    Time frame: week 24

  40. Assessment of BSA

    The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients.

    Time frame: week 24

  41. 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

    Time frame: week 40

  42. Assessment of BSA

    The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients.

    Time frame: week 40

  43. Assessment of BASDAI

    The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement

    Time frame: week 40

  44. 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

    Time frame: week 52

  45. Assessment of BSA

    The body surface area will be evaluated to measure the extend of Psoriasis in the included PsA patients.

    Time frame: week 52

  46. Assessment of BASDAI

    The Bath ankylosing spondylitis disease activity index will be performed for those patients who have radiological findings suspect for axial involvement

    Time frame: week 52

  47. Treatment adherence measured by patient diary

    Compliance with treatment will be determined by patient diary

    Time frame: through treatment period; normally 52 weeks

  48. Compliance measured by questionnaire CQR5

    The CQR5 consists of 5 questions addressing information on treatment compliance of the patient.

    Time frame: through treatment period; normally 52 weeks

  49. Quality of life measured by HAQ

    Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA

    Time frame: week 4

  50. Quality of life measured by EQ5D

    EQ5D is a standardised instrument for use as a measure of health outcome

    Time frame: week 4

  51. Quality of life measured by DLQI

    The Dermatology Life Quality Index is a 10-question validated questionnaire.

    Time frame: week 4

  52. Quality of life measured by EQ5D

    EQ5D is a standardised instrument for use as a measure of health outcome

    Time frame: week 16

  53. Quality of life measured by HAQ

    Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA

    Time frame: week 16

  54. Quality of life measured by DLQI

    The Dermatology Life Quality Index is a 10-question validated questionnaire.

    Time frame: week 16

  55. Quality of life measured by DLQI

    The Dermatology Life Quality Index is a 10-question validated questionnaire.

    Time frame: week 24

  56. Quality of life measured by EQ5D

    EQ5D is a standardised instrument for use as a measure of health outcome

    Time frame: week 24

  57. Quality of life measured by HAQ,

    Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA

    Time frame: week 24

  58. Quality of life measured by HAQ

    Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA

    Time frame: week 40

  59. Quality of life measured by EQ5D

    EQ5D is a standardised instrument for use as a measure of health outcome

    Time frame: week 40

  60. Quality of life measured by DLQI

    The Dermatology Life Quality Index is a 10-question validated questionnaire.

    Time frame: week 40

  61. Quality of life measured by HAQ

    Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA

    Time frame: week 52

  62. Quality of life measured by EQ5D

    EQ5D is a standardised instrument for use as a measure of health outcome

    Time frame: week 52

  63. Quality of life measured by DLQI

    The Dermatology Life Quality Index is a 10-question validated questionnaire.

    Time frame: week 52

  64. Assessment of Change in Dactylitis

    Functional assessment: Change in number and severity of digits involved) involved

    Time frame: week 4, 16, 24, 40 and week 52

  65. Assessment of Change in Enthesitis (LEI)

    functional outcome

    Time frame: week 4, 16, 24, 40 and week 52

  66. Assessment of mtNAPSI

    The modified target Nail Psoriasis Severity Index is used for evaluation of nail involvement in patients

    Time frame: week 4, 16, 24, 40 and week 52

  67. Ultrasound (US) assessment of joints and enthesis according to PASON22

    selected sites only

    Time frame: Week 4, 24 and week 52

  68. 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

    Time frame: each study visit (week 0 to week 52)

07

Study locations

1 site
  • CIRI
    Frankfurt am Main, Hessia 60526, Germany
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 2, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03148860
Lead sponsor
Dr. Frank Behrens
Collaborators
Janssen-Cilag Ltd.
Responsible party
Dr. Frank Behrens (Coordinating Investigator and representative of sponsor, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP) — Sponsor-investigator
First posted
May 11, 2017
Start date
Dec 15, 2016
Primary completion
Apr 12, 2021
Completion
Oct 21, 2021
Last update
Mar 2, 2022

Study contacts

Frank Behrens, MD
principal investigator · Fraunhofer IME

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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