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Switching from originator infliximab to biosimilar infliximab in Japanese patients with rheumatoid arthritis achieving clinical remission (the IFX-SIRIUS study I): Study protocol for an interventional, multicenter, open-label, single-arm and noninferiority clinical trial with clinical, ultrasound and biomarker assessments

Switching from originator infliximab to biosimilar infliximab in Japanese patients with rheumatoid arthritis achieving clinical remission (the IFX-SIRIUS study I): Study protocol for an interventional, multicenter, open-label, single-arm and noninferiority clinical trial with clinical, ultrasound and biomarker assessments

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The analysis population (FAS: Full analysis set) comprised 18 cases, and 18 cases were summarized. Continuous variables indicate the median (interquartile range), and categorical variables indicate the number (percentage) of cases. The age of the patients was 63 years (51, 72), with 6 males (33%) and 12 females (67%). They were 162 cm (154, 167) tall and weighed 54 kg (46, 63). Nine years (6, 12.3) had RA, 15 (83%) were RF positive, and 17 (94%) were anti-CCP antibody positive. The highest historical RF level was 122 IU/mL (39, 174), and the highest anti-CCP antibody level was 214 U/mL (100, 440). The baseline RF level was 20 IU/mL (10, 30) and the baseline anti-CCP antibody level was 39 U/mL (13, 148). The duration of Remicade treatment was 6.4 years (3.4, 9.5), and the duration of maintenance of clinical remission was 83 weeks (25, 151). Baseline Remicade dose was 4.5 mg/kg (3, 8.25) and dosing interval was 8 weeks (8, 8.75). The methotrexate dose at baseline was 8 mg/week (8, 10), and two patients (11%) were receiving concomitant prednisolone (PSL) at baseline at a dose of 4 mg/day (3.5, 4.5). Five patients were concomitantly treated with DMARDs other than methotrexate: 3 with iguratimod, 1 with tacrolimus, and 1 with tacrolimus, salazosulfapyridine, and iguratimod. Nine subjects (50%) had a history of smoking and 15 pack-years of smoking (8, 33). Fourteen subjects (78%) had 33 complications. The most common complication was osteoporosis in five cases (15.2%). The number of patients treated with biologic DMARDs or JAK inhibitors was 2 with etanercept, 1 with tocilizumab, 1 with abatacept, and 1 with tofacitinib.

The number of patients registered per institution was 5 from Kindai University Hospital, 3 from Kagawa University Hospital, 3 from Eiraku Clinic, 3 from Osaka Metropolitan University, 2 from Sasebo Chuo Hospital, 1 from Yoshitama Clinic for Rheumatic Diseases, 1 from Tobata General Hospital, and 1 from Fukushima Medical University Hospital. Nineteen participants were enrolled in this study. One of the enrolled subjects did not receive any study drug, leaving 18 subjects for the analysis (FAS).

[Adverse events] In the safety analysis set (18 patients), there were three adverse events (eczema, dry dermatitis, and COVID-19) that occurred from the start of treatment to 24 weeks (including illness). No serious adverse events were observed. All non-serious adverse events were grade 2 and moderate in severity (requiring minimal/local/non-invasive treatment for adverse events). No adverse events led to discontinuation of the study. [Illness] None.

[primary endpoint] The proportion of study subjects who experienced clinical relapse from baseline to 24 weeks after the start of treatment was 2 out of 18, or 11.1% (95% confidence interval: 0.031-0.328). [Secondary endpoints] The mean (SD) and median (IQR) changes from baseline to 12 and 24 weeks in the total GS score, total PD score, composite score, DAS28-ESR, and DAS28-CRP. The mean (SD), median (IQR) are listed in this order. Total GS score Change 12 weeks: 0.12 (0.93), 0 (0, 0) Change 24 weeks: 0.12 (1.7), 0 (-1, 0) Total PD score Change 12 weeks: 0.18 (0.53), 0 (0, 0) Change 24 weeks: 0.059 (0.43), 0 (0, 0) Composite score Change 12 weeks: 0.18 (0.95), 0 (0, 0) Change 24 weeks: 0.059 (0.43), 0 (-1, 0) DAS28-ESR Change 12 weeks: 0.026 (0.4), -0.06 (-0.22, 0.36) Change 24 weeks: 0.38 (0.75), 0.15 (-0.08, 0.81) DAS28-CRP Change 12 weeks: 0.14 (0.3), 0.08 (-0.01, 0.29) Change 24 weeks: 0.37 (0.69), 0.13 (-0.05, 0.54)

The proportion of study subjects experiencing clinical relapse was 2 of 18. DAS28-ESR and DAS28-CRP remained at remission levels at 12 and 24 weeks. The median change from baseline to 12 and 24 weeks for the ultrasonographic score was 0. There were 3 adverse events from the start of treatment to week 24, but none were serious, and there were no cases of illness or other serious safety problems.

Jan. 01, 2025

Aug. 22, 2025

https://doi.org/10.5582/ddt.2025.01044

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs071190030

Kawakami Atsushi

Nagasaki University Hospital

1-7-1 Sakamoto, Nagasaki

atsushik@nagasaki-u.ac.jp

Kawashiri Shinya

Nagasaki University Hospital

1-7-1 Sakamoto, Nagasaki

+81-95-819-7200

shin-ya@nagasaki-u.ac.jp

Complete

Oct. 11, 2019

Interventional

single arm study

open(masking not used)

historical control

single assignment

treatment purpose

1. Patients with 20 years older at the time of obtaining informed consent.
2. Patients with rheumatoid arthritis (RA) fulfilled the ACR/EULAR classification criteria for RA (2010).
3. Patients who have been treated with Remicade over 24 weeks and same dosage of Remicade over 12 weeks, and persisted with clinical remission (DAS28-ESR<2.6) on the last administration date of Remicade and the baseline visit.
4. Patients who give written informed consent after receiving sufficient information.

1. Patients treated with more than 10mg/day of prednisolone, except for using on Remicade injection date only.
2. Patients treated with Infliximab BS previously.
3. Patients treated with biological agents and JAK inhibitors for RA, except for Remicade and Denosumab.
4. Patients with a history of infusion reaction to Remicade required medication.
5. Patients treated with corticosteroid or anti-rheumatic drugs changed the dose within 8 weeks prior to baseline visit.
6. Patients treated with prohibited substances or prohibited therapy within 8 weeks prior to baseline visit.
7. Women who are currently pregnant or will not be compliant with a medically approved contraceptive regimen during and 6 months after the study period and lactating women. Men who will not be compliant with a contraceptive regimen during and 6 months after the study period.
8. Patients who jugged unsuitable for this study by the investigator.

Both

Rheumatoid arthritis

Rheumatoid arthritis patients who have been treated with Remicade over 24 weeks and persisted with clinical remission are switched to infliximab BS from Remicade.
The dose and infusion intervals of infliximab BS are kept unchanged from those of Remicade.

Clinical relapse rate

Changes of total power Doppler (PD) score by musculoskeletal ultrasound.
Changes of total gray scale (GS) score by musculoskeletal ultrasound.
Changes of combined score by musculoskeletal ultrasound.
Changes of DAS28-ESR.
Changes of DAS28-CRP.

+81-95-819-7229

Sept. 17, 2019

none