A Prospective, Randomized, Controlled, Open Label, Assessor-blinded, Parallel-group Phase III Clinical Trial to Evaluate the Impact of Tapering Systemic Immunosuppressive Therapy in a Treat-to-target Approach on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis
Overview
- Phase
- Phase 3
- Intervention
- Prednisolone
- Conditions
- Psoriatic Arthritis
- Sponsor
- University of Erlangen-Nürnberg Medical School
- Enrollment
- 270
- Locations
- 1
- Primary Endpoint
- Presence of MDA (minimal disease activity) 12 months after baseline.
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The rationale for this study is to investigate whether in psoriatic arthritis (PsA) patients in stable remission a reduction or complete discontinuation of immunosuppressive therapy can be achieved in a treat-to-target approach while maintaining in remission. Due to the lack of reliable data that answers the question of how to safely reduce medication in which patients, this study will test a pragmatic treatment algorithm that can be applied in clinical practice and that offers a gradual reduction with escape strategies in order to facilitate the maintenance of remission.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent obtained from the subject
- •Understanding of study procedures and willingness to abide by all procedures during the course of the study.
- •Adult subject; age range 18-≤75 years
- •Male or female subject
- •Diagnosis of PsA according to CASPAR criteria
- •Disease status "MDA" for at least 6 months
- •Subject should have been treated without alterations of therapy (fixed dose and drug) for at least 6 months with one or more of the following drugs:
- •i. csDMARD Leflunomid (e.g. Arava), Sulfasalazin (e.g. Azulfidine RA, Pleon RA), Methotrexate (e.g. Lantarel, Metex) AND/OR ii. bDMARD/tsDMARD: Etanercept (e.g. Enbrel, Erelzi, Benepali), Adalimumab (e.g. Humira, Amgevita, Imraldi, Hyrimoz), Infliximab (e.g. Remicade, Zessly, Inflectra), Golimumab (Simponi), Certolizumab (Cimzia), Abatacept (Orencia), Apremilast (Otezla), Ustekinumab (Stelara), Secukinumab (Cosentyx), Ixekizumab (Taltz), Tofacitinib (Xeljanz) AND/OR (c) glucocorticoids (≤5mg prednisolone equivalent).
- •Women of childbearing potential must be using a highly effective method of birth control.
- •Male subjects using an adequate contraceptive method at the investigator's discretion.
Exclusion Criteria
- •Diagnosis of any other rheumatological/ immunological disease such as rheumatoid arthritis, SLE, PSS, MCTD, M. Behcet or M. Wegener
- •Concomitant florid (not sufficiently adjusted under treatment) autoimmune disease such as autoimmune hepatitis or Hashimoto's disease
- •Use of any inadmissible medication (e.g. current treatment with DMARDs other than mentioned above or drugs under development)
- •Treatment with systemic glucocorticoids (daily dose \>5mg prednisolone equivalent) during the last 6 months before randomization. Intra-articular or entheseal injections of glucocorticoids do not constitute an exclusion criterion
- •Malignant disease currently under oncological treatment or history of a recent malignancy with moderate or high risk of relapse within 5 years prior to Screening
- •Existence of another disease including the presence of laboratory abnormalities which, at the discretion of the investigator, would result in a disproportionate risk to the patient concerned or confounds the ability to interpret data from the study
- •Any anti-inflammatory (excluding NSAIDs) or immunosuppressive therapy for other reasons than PsA or psoriasis during the last 3 months before Screening
- •Nursing mother or pregnant woman as verified by a positive pregnancy test
- •Known hypersensitivity to the IMPs or any of their formulation ingredients
- •Subject who is imprisoned or is lawfully kept in an Institution
Arms & Interventions
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Prednisolone
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Sulfasalazine
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Leflunomide
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Methotrexate
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Tofacitinib
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Apremilast
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Etanercept
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Adalimumab
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Infliximab
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Certolizumab pegol
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Golimumab
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Abatacept
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Secukinumab
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Ixekizumab
Reduction group
Individual previous stable dosage of glucocorticoids/DMARDs will be stepwise reduced according to a predefined algorithm
Intervention: Ustekinumab
Outcomes
Primary Outcomes
Presence of MDA (minimal disease activity) 12 months after baseline.
Time Frame: 12 months
The MDA status comprises the assessment of different domains of PsA, consisting of the following individual components: * swollen and tender joint count * tender entheseal point count * skin involvement (PASI)patient self-assessment of pain (VAS) * global disease activity status * subject's self-assessment of functional ability using Stanford Health Assessment Questionnaire disability index, (HAQ-DI) MDA is defined as the presence of 5 of the following 7 criteria: 1. tender joint count ≤1 2. swollen joint count ≤1 3. tender entheseal point count ≤1 (means: remission) 4. PASI ≤1 OR body surface area (BSA) ≤3% 5. patient pain VAS ≤15 6. patient global activity VAS ≤20 7. HAQ-DI ≤0.5
Secondary Outcomes
- Number of swollen and tender joints(12 months)
- Number of tender entheseal points: SPARCC (Spondyloarthritis Consortium of Canada)(12 months)
- Quality of life and health/disability: PsAID-12 (Psoriatic Arthritis Impact of Disease)(12 months)
- Quality of life and health/Disability: SF-36 (Short Form Health)(12 months)
- Proportion of patients with loss of MDA within 24 months after baseline(24 months)
- AE (Adverse Event)(12 months)
- Key secondary endpoint: PASDAS (Psoriatic Arthritis Disease Activity Score)(12 months)
- Key secondary endpoint: DAPSA (Disease Activity in PSoriatic Arthritis)(12 months)
- Number of tender entheseal Points: LEI (Leeds Enthesitis Index)(12 months)
- Number of tender entheseal Points: MASES (Maastricht Ankylosing Spondylitis Enthesitis Score)(12 months)
- Activity of psoriasis: PASI (Psoriasis Area and Severity Index)(12 months)
- Pain (VAS)(12 months)
- Biomarker levels(24 months)
- Key secondary endpoint: CPDAI (Composite Psoriatic Disease Activity Index)(12 months)
- Quality of life and health/disability: HAQ-DI (Stanford Health Assessment Questionnaire Disability Index)(12 months)
- Dactylitis counts(12 months)
- Activity of psoriasis: BSA (body surface area)(12 months)
- Activity of axial Involvement: BASDAI (Disease Activity of Ankylosing Spondylitis)(12 months)
- Time needed to restore MDA after readjustment of the DMARD therapy in subjects who lost MDA within the intervention period(12 months)
- Intervention-related events within the observation period of 24 months after baseline(24 months)
- SAR (Serious Adverse Reaction)(12 months)
- Quality of life and health/disability: DLQI (Dermatology Life Quality Index)(12 months)
- Quality of life and health/disability: ASQoL (Ankylosing Spondylitis Quality of Life)(12 months)
- Proportion of patients with loss of MDA within 12 months after baseline(12 months)
- Time to loss of MDA(12 months)
- AR (Adverse Reaction)(12 months)
- SAE (Serious Adverse Event)(12 months)
- SUSAR (Suspected Unexpected Serious Adverse Reaction)(12 months)