TY - JOUR
T1 - Methotrexate safety and efficacy in combination therapies in patients with early rheumatoid arthritis
T2 - a post-hoc analysis of a randomized controlled trial (NORD-STAR)
AU - Lend, Kristina
AU - Koopman, Frieda A
AU - Lampa, Jon
AU - Jansen, Gerrit
AU - Hetland, Merete L
AU - Uhlig, Till
AU - Nordström, Dan
AU - Nurmohamed, Michael
AU - Gudbjornsson, Bjorn
AU - Rudin, Anna
AU - Østergaard, Mikkel
AU - Heiberg, Marte S
AU - Sokka-Isler, Tuulikki
AU - Hørslev-Petersen, Kim
AU - Haavardsholm, Espen A
AU - Grondal, Gerdur
AU - Twisk, Jos W R
AU - van Vollenhoven, Ronald
N1 - This article is protected by copyright. All rights reserved.
PY - 2023/10/17
Y1 - 2023/10/17
N2 - OBJECTIVE: To investigate methotrexate safety and influence of dose on efficacy outcomes in combination with three different biological treatments and with active conventional treatment (ACT) in early rheumatoid arthritis (RA).METHODS: This post-hoc analysis included 812 treatment-naïve early RA patients who were randomized (1:1:1:1) in the NORD-STAR trial (NCT01491815) to receive methotrexate in combination with ACT, certolizumab-pegol, abatacept, or tocilizumab. Methotrexate safety, doses, and dose effects on Clinical Disease Activity Index (CDAI) remission were assessed after 24 weeks of treatment.RESULTS: Compared with ACT, the prevalence of methotrexate-associated side effects was higher when methotrexate was combined with tocilizumab (HR 1.48 [95% CI 1.20 to 1.84]), but not with certolizumab-pegol (HR 0.99 [0.79 to 1.23]) or with abatacept (HR 0.93 [0.75 to 1.16]). With ACT as the reference, methotrexate dose was significantly lower when used in combination with tocilizumab (β -4.65 [95% CI -5.83 to -3.46], p<0.001), with abatacept (β -1.15 [-2.27 to -0.03], p=0.04), and numerically lower in combination with certolizumab-pegol (β -1.07 [-2.21 to 0.07], p=0.07). Methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the treatment combinations.CONCLUSION: Methotrexate was generally well tolerated in combination therapies, but adverse events were a limiting factor in receiving the target dose of 25 mg/week, and these were more frequent in combination with tocilizumab versus active conventional treatment. On the other hand, methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the four treatment combinations at 24 weeks. This article is protected by copyright. All rights reserved.
AB - OBJECTIVE: To investigate methotrexate safety and influence of dose on efficacy outcomes in combination with three different biological treatments and with active conventional treatment (ACT) in early rheumatoid arthritis (RA).METHODS: This post-hoc analysis included 812 treatment-naïve early RA patients who were randomized (1:1:1:1) in the NORD-STAR trial (NCT01491815) to receive methotrexate in combination with ACT, certolizumab-pegol, abatacept, or tocilizumab. Methotrexate safety, doses, and dose effects on Clinical Disease Activity Index (CDAI) remission were assessed after 24 weeks of treatment.RESULTS: Compared with ACT, the prevalence of methotrexate-associated side effects was higher when methotrexate was combined with tocilizumab (HR 1.48 [95% CI 1.20 to 1.84]), but not with certolizumab-pegol (HR 0.99 [0.79 to 1.23]) or with abatacept (HR 0.93 [0.75 to 1.16]). With ACT as the reference, methotrexate dose was significantly lower when used in combination with tocilizumab (β -4.65 [95% CI -5.83 to -3.46], p<0.001), with abatacept (β -1.15 [-2.27 to -0.03], p=0.04), and numerically lower in combination with certolizumab-pegol (β -1.07 [-2.21 to 0.07], p=0.07). Methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the treatment combinations.CONCLUSION: Methotrexate was generally well tolerated in combination therapies, but adverse events were a limiting factor in receiving the target dose of 25 mg/week, and these were more frequent in combination with tocilizumab versus active conventional treatment. On the other hand, methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the four treatment combinations at 24 weeks. This article is protected by copyright. All rights reserved.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85182718243&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/37846618
U2 - https://doi.org/10.1002/art.42730
DO - https://doi.org/10.1002/art.42730
M3 - Article
C2 - 37846618
SN - 2326-5191
JO - Arthritis & Rheumatology
JF - Arthritis & Rheumatology
ER -