Baseline bony erosions and time-averaged DAS28 predict discontinuation of TNF inhibitors in rheumatoid arthritis

Min, Hong Ki; Kim, Se Hee; Lee, Sang‐Heon; Kim, Hae-Rim

doi:10.1038/s41598-022-24027-6

Cited by 3 publications

(2 citation statements)

References 36 publications

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“…Our results suggest a role of one-carbon metabolism in the efficacy of anti-TNF-α drugs, and may pave the way for more personalized interventions in the treatment of RA. In perspective, the development of an accurate prediction model based on a wide range of pharmacogenetic, metabolic [ 55 ], clinical [ 56 ], circulating microRNA [ 57 , 58 ], and serological [ 59 ] markers—which may influence the treatment response with an additive score significance—could tailor better personalized anti-TNF-α treatments for RA patients.…”

Section: Discussionmentioning

confidence: 99%

MTHFR c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis

Ravaei

Pulsatelli

Assirelli

et al. 2023

IJMS

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Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with a prevalence of 1%. Currently, RA treatment aims to achieve low disease activity or remission. Failure to achieve this goal causes disease progression with a poor prognosis. When treatment with first-line drugs fails, treatment with tumor necrosis factor-α (TNF-α) inhibitors may be prescribed to which many patients do not respond adequately, making the identification of response markers urgent. This study investigated the association of two RA-related genetic polymorphisms, c.665C>T (historically referred to as C677T) and c.1298A>C, in the MTHFR gene as response markers to an anti-TNF-α therapy. A total of 81 patients were enrolled, 60% of whom responded to the therapy. Analyses showed that both polymorphisms were associated with a response to therapy in an allele dose-dependent manner. The association for c.665C>T was significant for a rare genotype (p = 0.01). However, the observed opposite trend of association for c.1298A>C was not significant. An analysis revealed that c.1298A>C, unlike c.665C>T, was also significantly associated with the drug type (p = 0.032). Our preliminary results showed that the genetic polymorphisms in the MTHFR gene were associated with a response to anti-TNF-α therapy, with a potential significance for the anti-TNF-α drug type. This evidence suggests a role for one-carbon metabolism in anti-TNF-α drug efficacy and contributes to further personalized RA interventions.

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Section: Discussionmentioning

confidence: 99%

MTHFR c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis

Ravaei

Pulsatelli

Assirelli

et al. 2023

IJMS

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“…The severity of rheumatoid arthritis was assessed on the basis of the disease activity score (DAS), functional impact using the HAQ score, structural damage according to the sharp score, and the presence of extra-articular manifestations [18][19][20] . RF isotypes were measured using a latex agglutination test according to the manufacturer's instructions (Biosystems SA, Barcelona, Spain).…”

Section: Data Gatheringmentioning

confidence: 99%

HLA class II antigen (DRB1 and DQB1) and rheumatoid arthritis in a Tunisian population: Relation to autoantibodies and disease severity

Boussaid,

Tbini,

Makhlouf

et al. 2023

Trends Immunother.

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We aimed to evaluate the association of HLA DRB1 and DQB1 alleles with rheumatoid arthritis (RA), and to investigate their relationship with anti-citrullinated peptide antibodies (ACPA) and RA severity. We performed a case-control study of 81 RA patients compared with 100 healthy controls. Sociodemographic data, disease activity scores, functional impact, structural damage, ACPA, rheumatoid factor (RF), and HLA DRB1 and DQB1 alleles were determined. Forty-six patients expressed HLA DRB1, predominantly DRB1*04. These alleles were more frequent in RA patients than in controls. DRB1*04:05 was the most associated allele with RA susceptibility, 54.5% of RF-positive patients expressed DRB1*04:05 with a significant correlation. Similarly, a highly significant association with DRB1*15:01 and RF positivity was found. DRB1*01:01, 04:05, 11:01, and 15:01 were associated with the presence of ACPA. Patients with DRB1 alleles had more extraarticular manifestations (EAM). Multivariate analysis concluded that DRB1*04:05 was only associated with ACPA positivity. Regarding DQB1, DQB1*03:02 was the most associated with RA. DQB1*02:01, 03:01, 03:02, 05:01, and 06:01 were associated with RF-positive RA. DQB1*06:01 was associated with ACPA. Only HLA DQB1*02:01 and 06:01 were associated with the presence of EAM. DAS28 was reduced in the presence of DQB1. HAQ > 0.5 were correlated with DQB1 alleles. In addition, there was more structural damage in RA encoding for DQB1. In linear regression, DQB1*06:01 were associated with RF positivity, but there was no association with the other parameters. Our study confirmed that DRB1 and DQB1 expression was significantly associated with ACPA, increased HAQ, increased sharp score, and the presence of EAM.

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Risk factors for interstitial lung disease in rheumatoid arthritis: a cohort study from the KOBIO registry

Min,

Kim,

Lee

et al. 2023

Therapeutic Advances in Musculoskeletal

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Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan–Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p < 0.001). Multivariate Cox regression analysis identified older age (HR = 1.057, p = 0.001), male sex (HR = 2.824, p = 0.007), time-averaged DAS28 (HR = 2.241, p < 0.001), and rheumatoid factor titer (HR = 1.009, p = 0.007) as having a significantly increased HR for ILD occurrence. Conclusion: ILD is a rare but critical extra-articular symptom of RA patients. Therefore, RA patients with the above risk factors should be monitored carefully for ILD development.

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Baseline bony erosions and time-averaged DAS28 predict discontinuation of TNF inhibitors in rheumatoid arthritis

Cited by 3 publications

References 36 publications

MTHFR c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis

MTHFR c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis

HLA class II antigen (DRB1 and DQB1) and rheumatoid arthritis in a Tunisian population: Relation to autoantibodies and disease severity

Risk factors for interstitial lung disease in rheumatoid arthritis: a cohort study from the KOBIO registry

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