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Investigation on the safety and utility of apremilast for the treatment of refractory rash in patients with dermatomyositis (ACDM)

Investigation on the safety and utility of apremilast for the treatment of refractory rash in patients with dermatomyositis (ACDM)

5

Adult patients from 20 to 80 years old, diagnosed with dermatomyositis by Bohan and Peter criteria, with dermatomyositis-associated refractory cutaneous manifestations were recruited. The median age of the 5 enrolled patients was 64 (range 37-71) years. Although 4 of the 5 patients were diagnosed as classic dermatomyostis at the disease onset, All patients were not complicated with active myositis, arthritis, interstitial lung disease and malignancy at the enrollment of this study. The median disease duration of the 5 patients was 8 (range 5-40) years. All patients were treated with low-dose oral prednisolone while 4 patients were additionally treated with oral calcineurin inhibitors (tacrolimus or ciclosporin). All patients had dermatomyositis-associated refractory cutaneous manifestations were refractory to pretreatments with topical steroid and low-dose oral corticosteroid with/without oral calcineurin inhibitors, and persistent for more than> 1 year despite oral prednisolone and/or oral calcineurin inhibitors. Baseline severities of cutaneous involvements in these patients are shown in Table 2. The median (range) values of CDASI total activity, total damage, and total scores were 33 (15-49), 6 (2-7), and 39 (17-56), respectively. The median (range) values for VAS and DLQI and VAS were 6 (3-8) and 6 (2-10) and 6 (3-8), respectively. Serum levels of creatine kinase were not elevated in any participant.

One patient (Case 4) who experienced moderate diarrhea and nausea from 2 days after apremilast initiation withdrew from this study 16 days after the initiation, while another patient (Case 5) who experienced vomiting from 6 days after apremilast initiation did so 37 days after the initiation.

Adverse events, particularly apremilast-associated digestive symptoms, occurred in 4 patients (80.0%) who experienced diarrhea (3 patients, Case 2-4), nausea (1 patient, Case 4), and vomiting (1 patient, Case 5) in addition to mild headache (1 patient, Case 3), and inflammatory atheroma in 1 patient (Case 1) who had experienced inflammatory atheroma several times before enrolling in this study.

The median (ranges) rates of decreased CDASI total activity, total damage, and total scores were 39.4% (20.0-61.2%), 0% (0-16.7%), and 30.8% (15.9-53.6%), respectively. The VAS for itching was slightly improved in 1 patient 12 weeks after initiation. DLQI was improved in 2 patients.

As apremilast was effective, with expected and recoverable digestive adverse events (diarrhea), in patients with refractory and recurrent dermatomyositis-associated cutaneous manifestations in this first Phase Ib study, it can be suggested as a possible treatment when aggressive immunosuppressive therapies with high-dose systemic corticosteroid and/or immunosuppressive agents for other manifestations, myositis, and interstitial lung disease, are not required.

Mar. 31, 2023

Oct. 03, 2021

https://onlinelibrary.wiley.com/doi/10.1111/1346-8138.16179

Yes

1. When data sharing is carried out, as a general rule, joint research with the representative researcher is carries out, and the representative researcher decided whether or not the final data can be provided. 2. We would provide the data after publication of the main analysis results 3. We would publish the fact that the data was provided on the University of Tsukuba website 4. We would ask the representative researcher to send the analysis program, log, and output

https://jrct.mhlw.go.jp/latest-detail/jRCTs031200005

Okiyama Naoko

University of Tsukuba Hospital

2-1-1 Amakubo, Tsukuba, Ibaraki

naoko.okiyama@md.tsukuba.ac.jp

Okiyama Naoko

University of Tsukuba Hospital

2-1-1 Amakubo, Tsukuba, Ibaraki

+81-29-853-3128

naoko.okiyama@md.tsukuba.ac.jp

Complete

April. 10, 2020

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Patients with a diagnosis of dermatomyositis
2) Patients still having cutaneous disease activity for more than 12 weeks despite of topical steroid
3) Must be 20 - 80 year-old at time of signing the informed consent form
4) Patients who have been fully informed after participating in this study, and make informed consents with sufficient understanding
5) Patients who are outpatient or hospitalized in our hospital

1) Recieving or planning to recive for 4 months immuno-inhibitory biologic agetns, JAK inhibitors, or cancer chmotheraphy
2) Recieving or planning to recive for 4 months CYP3A4 inducers
3) Pregnant or women who do not agree to contraception during the study periodlactating women
4) Lactating woman
5) Haveing severe renal dysfunction (creatinine clearance < 30 ml/min)
6) Haveing active infectional disease
7) Patients who the investigators assess to unsuitable as subjects for the study, including patients with history of hypersensitivity to the component

Both

Dermatomyositis

Oral administration of apremilast: Start with 10 mg of oral dose and gradually increase the dose until day 5, 30mg twice a day from day 6 (morning / evening) for a total of 12 weeks

Collagen disease, inflammatory myopathy, cutaneous manifestation

PDE4 inhibitor

D003882

C505730

Safety

CDASI, serum profile of cytokines, VAS for itching, DLQI

+81-29-853-3914

Feb. 27, 2020

none