Prevalence and predictive factors of difficult-to-treat rheumatoid arthritis: the KURAMA cohort

Watanabe, Ryu; Hashimoto, Motomu; Murata, Koichi; Murakami, Kosaku; Tanaka, Masao; Ohmura, Koichiro; Ito, Hiromu; Matsuda, Shinya

doi:10.1080/25785826.2021.1928383

Cited by 40 publications

(21 citation statements)

References 26 publications

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“…Therefore, this review must also come with the usual caveat that it might not be generalizable to other institutions with different patient populations and different approaches to management of RA with TTs. However, our result of ∼10% of patients within our cohort having RefRA is comparable to other studies in the area [ 10 , 20 , 21 ].…”

Section: Discussionsupporting

confidence: 89%

Single-centre experience of refractory rheumatoid arthritis

Fitton

Melville

Naraghi

et al. 2022

Rheumatology Advances in Practice

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Objectives To evaluate the proportion of RA patients that are refractory to multiple targeted therapies in a real-world cohort of patients in a tertiary rheumatology referral centre. To describe patterns of drug sequencing associated with the development of RefRA. To identify if there is a subgroup of RefRA patients in whom successive drugs have shown primary lack of efficacy. Methods Patients at a single centre were defined as refractory if they had failed two or more classes of targeted therapy (TT) and were identified from a dedicated TT clinic database. Reasons for drug failure were recorded and patients categorised pragmatically as having mild (2 biologic DMARD (bDMARD) class failure), moderate (≥3 bDMARD class failure) or severe (≥2 bDMARD class and JAK inhibitor failure) refractory disease. Results 172 patients were identified as RefRA (>10% of our TT exposed cohort); median (IQR) TT exposures of 4 (2), 81.5% female, 82% seropositive, mean (SD) age of 63 (12.3) years. Detailed analysis of 60 patients showed a median (IQR) disease duration of 22 (10.75) years, median (IQR) time from diagnosis to initiation of first TT of 5 (10) years, and mean (SD) baseline DAS28CRP prior to starting 1st line TT of 5.91 (0.84). Among RefRA patients, 15% were severe refractory, and 6% had demonstrated no clinical response to any TT. Conclusion A small proportion of patients have “true” RefRA. Most patients fail multiple therapies due to a combination of inefficacy and adverse events.

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Section: Discussionsupporting

confidence: 89%

Single-centre experience of refractory rheumatoid arthritis

Fitton

Melville

Naraghi

et al. 2022

Rheumatology Advances in Practice

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“…Under specific stimuli, circulating monocytes migrate to a specific location in the bones and then fuse with each other to become mature multinucleated osteoclasts (3,4). Current therapies for RA are not effective in all patients, recently several studies reported that approximately 3~10% of RA patients have been estimated as "difficult-to-treat" RA which defined by multiple biologic disease modifying anti rheumatic drugs (bDMARDs)/targeted synthetic DMARDs failure, rapid progressive bone destruction, moderate disease activity despite appropriate treatment and so on (5)(6)(7). Moreover, not all patients can be treated due to the high cost of medication and the occurrence of adverse events such as infection.…”

Section: Introductionmentioning

confidence: 99%

The monocyte-to-osteoclast transition in rheumatoid arthritis: Recent findings

Iwamoto

Kawakami

2022

Front. Immunol.

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation leading to joint destruction and deformity. The crucial role of osteoclasts in the bone erosion in RA has been demonstrated. Deregulated osteoclastogenesis which is affected by environmental factors including the inflammatory state, as well as genetic and epigenetic factors, is one of hallmarks of RA pathogenesis. An enhanced-monocyte-to-osteoclast transition plays an important role in osteoclast upregulation in RA because under specific stimuli, circulating monocytes might migrate to a specific location in the bones and fuse with each other to become mature multinucleated osteoclasts. To understand the mechanism of bone damage in RA and to develop novel treatments targeting osteoclast upregulation, it is important to clarify our understanding of the monocyte-to-osteoclast transition in RA. Several potential targets which inhibit both inflammation and osteoclastogenesis, as well as regulators that affect the monocyte-to-osteoclast transition have been revealed by recent studies. Here, we review the factors affecting osteoclastogenesis in RA, summarize the anti-osteoclastogenic effects of current RA treatments, and identify promising therapeutic targets relating to both inflammation and osteoclastogenesis.

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“…Subsequently, the proportion of patients who fulfill the criteria of D2T RA or who show multiple b/tsDMARD resistance in patients with RA has been reported in several cohort studies worldwide, mostly in the 5–20% range ( 15 – 19 ). In our cohort, 7.9% of 672 patients with RA fulfilled the definition of D2T RA ( 20 ). These results may reflect the widespread use of high-dose MTX and b/tsDMARDs following the treat-to-target strategy, resulting in relatively favorable disease control in 80–90% of patients with RA.…”

Section: Current Status and Unsolved Problems Of Difficult-to-treat Ramentioning

confidence: 98%

“…For example, in our cohort, 21.2% showed moderate to high disease activity at the last visit, with no history of b/tsDMARD use. This population may have included patients with limited access to b/tsDMARDs owing to high costs ( 20 ). In the definition of D2T RA, the following is described in the footnote: failure of ≥ 2 b/tsDMARDs unless restricted by access to treatment due to socioeconomic factors ( 6 ) ( Figure 1 ).…”

Section: Current Status and Unsolved Problems Of Difficult-to-treat Ramentioning

confidence: 99%

“…In our previous study, D2T RA patients had significantly higher rheumatoid factor (RF) levels, higher disease activities, more impaired physical functions, and a higher prevalence of lung and neurological diseases at baseline than non-D2T RA patients. In a multivariate analysis, high RF levels, high disease activity at baseline, and coexisting pulmonary disease were associated with D2T RA ( 20 ).…”

Section: Current Status and Unsolved Problems Of Difficult-to-treat Ramentioning

confidence: 99%

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Difficult-to-treat rheumatoid arthritis: Current concept and unsolved problems

Watanabe¹,

Okano²,

Gon³

et al. 2022

Front. Med.

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Over the past several decades, the treatment of rheumatoid arthritis (RA) has advanced significantly, and clinical, structural, and functional remission are achievable therapeutic goals. However, a substantial number of patients show resistance to multiple drugs. In particular, patients whose disease activity cannot be controlled despite the use of two or more biological disease-modifying antirheumatic drugs (DMARDs) or targeted synthetic DMARDs (tsDMARDs) with different mechanisms of action (MOA) have recently been referred to as having difficult-to-treat RA (D2T RA). D2T RA is a heterogeneous and multifactorial disease state, and the major problems are uncontrolled disease activity and decreased quality of life, as well as the economic burden due to frequent healthcare utilization and multiple admissions. Since the concept of D2T RA is relatively new and publication regarding D2T RA is limited, the mechanism underlying DMARD inefficacy and which factors form a “difficult-to-treat” state in such patients are not yet fully understood. It is also possible that factors contributing to D2T RA may differ by patient, sex, country, and race. The present Mini Review introduces the current concept and unsolved problems of D2T RA, including the definition, prevalence, and factors contributing to D2T RA. We then discuss the management and therapeutic strategies for D2T RA. Finally, we explore a clinical approach to prevent patients from developing D2T RA.

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Prevalence and predictive factors of difficult-to-treat rheumatoid arthritis: the KURAMA cohort

Cited by 40 publications

References 26 publications

Single-centre experience of refractory rheumatoid arthritis

Single-centre experience of refractory rheumatoid arthritis

The monocyte-to-osteoclast transition in rheumatoid arthritis: Recent findings

Difficult-to-treat rheumatoid arthritis: Current concept and unsolved problems

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