Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): a randomised, open-label, non-inferiority trial

Tamai, H; Ikeda, K; Miyamoto, T; Taguchi, H; Kuo, CF; Shin, K; Hirata, S; Okano, Y; Sato, S; Yasuoka, H; Kuwana, M; Ishii, T; Kameda, H; Kojima, T; Taninaga, T; Mori, M; Miyagishi, H; Sato, Y; Tsai, WC; Takeuchi, T; Kaneko, Y; MIRACLE study collaborators

doi:10.1016/s2665-9913(23)00070-x

Rheumatoid arthritis

Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): a randomised, open-label, non-inferiority trial

Lancet RheumatolPublished April 2023Randomised controlled trial

Primary result · SDAI remissionResultAdjusted risk difference 6.4% 90% CI −7.0 to 19.8

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Authors' conclusion

The MIRACLE study showed that the efficacy of adalimumab combined with reduced methotrexate dose was not inferior to that with the maximum tolerated methotrexate dose, with a tendency to a better safety profile.

Study context

Population: MTX-naive patients with RA and disease duration <2 years, 24 secondary or tertiary care hospitals in Japan, South Korea and Taiwan; randomised if not in Simplified Disease Activity Index (SDAI) remission at week 24 on MTX titrated to maximum tolerated dose291 in full analysis set
Participants: 300 patients

Comparison: Adalimumab plus reduced-dose MTX vs adalimumab plus maximum tolerated dose of MTX
Reduced-dosen = 66
Maximum tolerated dosen = 68reference
MTX monotherapyn = 105
Primary endpoint: Non-inferiority of adalimumab plus reduced-dose MTX to adalimumab plus maximal-dose MTX based on SDAI remission
Follow-up: Week 48

Methodological detailsopen-label, non-inferiority, multicentre (24 hospitals)

Open-label
Non-inferiority
Multicentre (24 hospitals)

Primary result

SDAI remission

Adjusted risk difference

6.4%

90% CI −7.0 to 19.8

Events by treatment group

Maximum tolerated dose38%25

Reduced-dose44%27

Reduced-dosevs Maximum tolerated dose

adjusted risk difference 6.4% (90% CI −7.0 to 19.8)

As reported in the abstract

Further findings

Deaths · week 24 to 48

No deaths

Safety

Outcome	Reduced-dose	Maximum tolerated dose	MTX monotherapy	P value
Adverse events after week 24Maximum tolerated dose vs Reduced-dose · safety analysis set	20%	35%	— not stated in the abstract	P = 0.054
Serious adverse events, week 24 to 48	3 events	5 events	6 events

— not stated in the abstract

Serious adverse events, week 24 to 48 — Total serious adverse events: 14

Reference

Authors: Tamai H, Ikeda K, Miyamoto T, Taguchi H, Kuo CF, Shin K, et al.
All 22 authors
Tamai H, Ikeda K, Miyamoto T, Taguchi H, Kuo CF, Shin K, Hirata S, Okano Y, Sato S, Yasuoka H, Kuwana M, Ishii T, Kameda H, Kojima T, Taninaga T, Mori M, Miyagishi H, Sato Y, Tsai WC, Takeuchi T, Kaneko Y, MIRACLE study collaborators
Journal: The Lancet Rheumatology
Published: April 2023
DOI: 10.1016/s2665-9913(23)00070-x
PubMed: 38251524
Registration: NCT03505008

Topic: Rheumatoid arthritis

Intervention details

Reduced-dose: adalimumab (40 mg biweekly) combined with a reduced dose of MTX
Maximum tolerated dose: adalimumab (40 mg biweekly) combined with a continued maximum tolerated dose of MTX
MTX monotherapy: patients who achieved SDAI remission at week 24 and continued MTX monotherapy through week 48 (not randomised)

Key notes

Met the non-inferiority margin of −15%
Modified full-analysis set

More notes

Non-inferiority margin −15%, two-sided 90% CI
Non-inferiority met

Original publication

Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): a randomised, open-label, non-inferiority trial. Lancet Rheumatol. Published April 2023. doi:10.1016/s2665-9913(23)00070-x

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