Enthesitis M07.0 M07.3
Conditions
Interventions
Group 1: Drug: apremilast 30mg 1-0-1 according to approval
treatment for 24 weeks.
Study type: interventional, prospective, single-arm
not placebo controlled
One-armed = there is no comparison group.
Open = No blinding is applied. All persons are aware of the group assignment.
Study phase: Phase IVb
Sponsors
Universitätsklinikum Freiburg
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Male or female, age = 18 years. 2. The diagnosis of psoriatic arthritis should be confirmed during and/or fulfilled at screening according to CASPAR classification criteria. Family history of psoriasis and/or personal history of dactylitis is not mandatory, but can be used in order to fulfill CASPAR classification criteria. 3. If the diagnosis of psoriatic arthritis as per CASPAR classification criteria is already fulfilled, diagnosis should be not older than 6 months, and the patients should have had an inadequate response or have been intolerant to a prior DMARD therapy (not more than two doses shall have been received). NSAIDs and fumaric acid as prior treatments are allowed. 4. Musculoskeletal symptom duration should not be longer than 12 months before screening. 5. Plaque psoriasis (history of and/or active disease) as confirmed by a dermatologist (biopsy encouraged, but not mandatory). 6. Nail psoriasis confirmed by a dermatologist; in doubtful cases, fungal infection should be ruled out. Active disease in at least one finger or toenail at both screening and baseline is required. 7. Presence of arthralgia (mechanical reason should be ruled out). 8. Active enthesitis confirmed by MSUS, and prevalent at both screening and baseline. 9. Negative for rheumatoid factor AND ACPA; ANA within normal range. 10. If patients are on NSAIDs, a stable dose shall be kept during 2 weeks before baseline. Moreover, patients are encouraged to maintain a stable NSAID-dose during the course of the study; in the case of a flare however, NSAIDS can be used as a rescue medication (please see section on rescue medication for details).
Exclusion criteria
Exclusion criteria: 1. Unwillingness or incapacity of adherence to study protocol 2. Musculoskeletal symptom duration > 12 months before screening 3. Pregnant or breastfeeding WOCBP, or women that plan to become pregnant during the course of the study or up to 3 months thereafter; women or men unwilling to use adequate methods of contraception such as (but not limited to) hormonal implants or hormonal contraceptives. 4. Positivity of rheumatoid factor, or ACPA or elevated concentration of ANA. 5. Iritis / anterior uveitis currently or in the last 6 months before first dose of study drug. 6. Any joint or enthesial infiltration or operation during 10mg/d = 2 weeks before baseline. 9. Pre-treatment of psoriatic arthritis with PDE-4-inhibitors, JAK-inhibitors, or any fusion proteins, or biological or conventional DMARDs other than methotrexate. 10. Use of any investigational drug other than study medication. 11. Hypersensitivity to apremilast or one of the other ingredients of the film-coated tablet. 12. Any other rheumatologic or autoimmune disease such as, but not limited to, rheumatoid arthritis, other spondyloarthrites than PsA, IBD, connective tissue disease, or MS. Patients with Hashimoto’s disease are eligible if the patient is euthyroid; substitution of thyroid hormones is not prohibited, if required by the patient and prescribed by a physician according to local guidelines. 13. Patients with fibromyalgia or another pain syndrome. 14. Any other skin disease despite psoriasis aggravating or inhibiting proper clinical examination. 15. Any other nail disease than nail psoriasis aggravating or inhibiting proper clinical examination. 16. Active malignant disease or history of malignoma < 5 years before baseline (adequately treated cervical carcinoma, squamous cell carcinoma and basalioma are allowed). 17. History of or active depression or any other psychological illness, which places the participant at an incalculable risk while undergoing PDE-4 inhibitor treatment to the opinion of the investigator. 18. Patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sensitivity and specificity including 95% confidence intervals of MSUS in Power Doppler mode using a 4-graded score compared to clinical assessment of enthesitis at week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary endpoint is the relative improvement of enthesitis at week 24 assessed by MSUS in Power Doppler mode using a 4-graded score. Further secondary objectives are: 1. MSUS assessments: - Sensitivity and specificity including 95% confidence intervals of MSUS in Power Doppler mode using a 4-graded score compared to clinical assessment via SPARCC and MASES at weeks 2, 4, 8, 12 and 16. - The relative regression of number of inflamed entheses assessed by MSUS in PD-mode at weeks 2, 4, 8, 12, 16 and 24 compared to baseline. - The relative improvement of enthesitis assessed by MSUS in PD-mode at screening, baseline, weeks 2, 4, 8, 12, and 16 (week 24 left out; it’s the primary objective) - Mean change of prevalence and number of morphological changes (including the above mentioned changes in morphology, and at bony insertion) of entheses in B-mode at weeks 2, 4, 8, 12, 16 and 24 compared to baseline. - Mean change of morphological changes of tendons in B-mode at weeks 2, 4, 8, 12, 16 and 24 compared to baseline. - The relative improvement of tendinitis assessed by MSUS in PD-mode at weeks 2, 4, 8, 12, 16 and 24 compared to baseline. - The relative improvement of inflamed soft tissue around tendons assessed by MSUS in PD-mode (peritendinitis; refers to tendons without tendon sheets) at weeks 2, 4, 8, 12, 16 and 24 compared to baseline. - The relative improvement of inflamed tendon sheets assessed by MSUS in B- and PD-mode (tenosynovitis) at weeks 2, 4, 8, 12, 16 and 24 compared to baseline. - The relative improvement of tenosynovitis assessed by MSUS in B- and PD-mode (grades 0-3) at weeks 2, 4, 8, 12, 16 and 24 compared to baseline. - The relative improvement of joint effusion, as well as B- and PD-mode synovitis and synovial hypertrophy (grades 0-3) at weeks 2, 4, 8, 12, 16 and 24 compared to baseline. - Relative change of numbers of bone erosions at the entheses as well as in periarticular bone at week 24 compared to baseline (erosions at periarticular bone and | — |
Countries
Germany
Outcome results
None listed