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Completed

NCT Number: NCT03148860

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

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.

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Key information

Conditions

Psoriatic Arthritis Arthritis Arthritis, Psoriatic Bone Diseases Joint Diseases Musculoskeletal Diseases Psoriasis Skin Diseases Skin Diseases, Papulosquamous Skin and Connective Tissue Diseases Spinal Diseases Spondylarthritis Spondylarthropathies Spondylitis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CIRI

Frankfurt am Main, Hessia, 60526, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

methotrexate

Drug

subjects will receive once weekly 15 mg (3 capsules) MTX

Ustekinumab

Drug

subject will receive Ustekinumab open-label over a treatment period of 52 weeks

Other names: Stelara

Placebo

Other

subjects will receive once weekly 3 capsules PLC to MTX

Primary outcomes

  1. 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.

Secondary outcomes

  1. Assessment of mean DAS28 at week 52

    Time frame: 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.

  2. Assessment of DAS28

    Time frame: 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.

  3. Assessment of DAS28

    Time frame: week 16

    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.

  4. Assessment of DAS28

    Time frame: week 24

    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.

  5. Assessment of DAS28

    Time frame: week 40

    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.

  6. Assessment of DAS28

    Time frame: 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.

  7. change in DAS28

    Time frame: 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.

  8. change in DAS28

    Time frame: baseline to week 16

    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.

  9. change in DAS28

    Time frame: baseline to week 24

    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.

  10. change in DAS28

    Time frame: baseline to week 40

    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.

  11. change in DAS28

    Time frame: baseline to 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.

  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)

    Time frame: week 4

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

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

    Time frame: week 16

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

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

    Time frame: week 24

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

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

    Time frame: week 40

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

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

    Time frame: week 52

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

  22. ACR (20/50/70) response

    Time frame: 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

  23. ACR (20/50/70) response

    Time frame: week 16

    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

  24. ACR (20/50/70) response

    Time frame: week 24

    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

  25. ACR (20/50/70) response

    Time frame: week 40

    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

  26. ACR (20/50/70) response

    Time frame: week 52

    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

  27. Change in ACR core set

    Time frame: baseline to week 4

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

  28. Change in ACR core set

    Time frame: baseline to week 16

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

  29. Change in ACR core set

    Time frame: baseline to week 24

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

  30. Change in ACR core set

    Time frame: baseline to week 40

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

  31. Change in ACR core set

    Time frame: baseline to week 52

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

  32. Assessment of PASI

    Time frame: week 4

    The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients

  33. Assessment of BASDAI

    Time frame: week 4

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

  34. Assessment of BSA

    Time frame: week 4

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

  35. Assessment of BASDAI

    Time frame: week 16

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

  36. Assessment of PASI

    Time frame: week 16

    The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients

  37. Assessment of BSA

    Time frame: week 16

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

  38. Assessment of BASDAI

    Time frame: week 24

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

  39. Assessment of PASI

    Time frame: week 24

    The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients

  40. Assessment of BSA

    Time frame: week 24

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

  41. Assessment of PASI

    Time frame: week 40

    The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients

  42. Assessment of BSA

    Time frame: week 40

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

  43. Assessment of BASDAI

    Time frame: week 40

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

  44. Assessment of PASI

    Time frame: week 52

    The Psoriasis Area and Severity Index (PASI) is used for evaluation of severity and extend of skin involvement of the included patients

  45. Assessment of BSA

    Time frame: week 52

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

  46. Assessment of BASDAI

    Time frame: week 52

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

  47. Treatment adherence measured by patient diary

    Time frame: through treatment period; normally 52 weeks

    Compliance with treatment will be determined by patient diary

  48. Compliance measured by questionnaire CQR5

    Time frame: through treatment period; normally 52 weeks

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

  49. Quality of life measured by HAQ

    Time frame: week 4

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

  50. Quality of life measured by EQ5D

    Time frame: week 4

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

  51. Quality of life measured by DLQI

    Time frame: week 4

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

  52. Quality of life measured by EQ5D

    Time frame: week 16

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

  53. Quality of life measured by HAQ

    Time frame: week 16

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

  54. Quality of life measured by DLQI

    Time frame: week 16

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

  55. Quality of life measured by DLQI

    Time frame: week 24

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

  56. Quality of life measured by EQ5D

    Time frame: week 24

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

  57. Quality of life measured by HAQ,

    Time frame: week 24

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

  58. Quality of life measured by HAQ

    Time frame: week 40

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

  59. Quality of life measured by EQ5D

    Time frame: week 40

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

  60. Quality of life measured by DLQI

    Time frame: week 40

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

  61. Quality of life measured by HAQ

    Time frame: week 52

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

  62. Quality of life measured by EQ5D

    Time frame: week 52

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

  63. Quality of life measured by DLQI

    Time frame: week 52

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

  64. Assessment of Change in Dactylitis

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

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

  65. Assessment of Change in Enthesitis (LEI)

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

    functional outcome

  66. Assessment of mtNAPSI

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

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

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

    Time frame: Week 4, 24 and week 52

    selected sites only

  68. Frequency and seriousness of adverse events as reported and documented in Case report form

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Dr. Frank Behrens

Other

Collaborators

  • Janssen-Cilag Ltd.

Registry information

Official study title

Impact of Concomitant Methotrexate on Efficacy, Safety and Adherence of Ustekinumab-treatment in Patients With Active Psoriasis Arthritis

Acronym: MUST

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
May 11, 2017
Registry last updated
Mar 2, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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