Abstract
Factors influencing prognosis after administration of the last biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) to patients with difficult-to-treat rheumatoid arthritis (D2T_RA) were evaluated in a clinical setting. RA patients who met the EULAR definition of D2T_RA were recruited. These patients were grouped according to success/failure. Success was defined as sustained within light disease activity or discontinued after clinical remission, and all of the following were met, including glucocorticoid (GCS) < 7.5 mg/day, no rapid radiographic progression, and improved quality of life from the beginning of the b/tsDMARD (baseline). Failure was defined as any other condition from success. The primary endpoint of the study was success or failure at 12 months after baseline. Factors influencing success/failure were statistically evaluated. A total of 71 D2T_RA patients were selected, 22 were in the success group and 49 in the failure group. For patients taking GCS and methotrexate (MTX) ≤ 8.6 mg/week, only one was included in the success group and the other 24 were included in the failure group (p < 0.001). Of the 18 patients without GCS and with MTX ≥ 8.7 mg, 12 patients whose 28-joint disease activity score ≤ 1.90 at 3 months or ≤ 2.54 at 6 months were in the success group (p < 0.01). D2T_RA patients with GCS or MTX ≤ 8.6 mg at baseline are considered to be at high risk of repeat D2T_RA. Patients with no GCS and MTX ≥ 8.7 mg are more likely to withdraw from D2T_RA if their disease activity is tightly controlled.
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References
Kearsley-Fleet L, Davies R, De Cock D, Watson KD, Lunt M, Buch MH, Isaacs JD, Hyrich KL (2018) Biologic refractory disease in rheumatoid arthritis: results from the British Society for rheumatology biologics register for rheumatoid arthritis. Ann Rheum Dis 77:1405–1412. https://doi.org/10.1136/annrheumdis-2018-213378
de Hair MJH, Jacobs JWG, Schoneveld JLM, van Laar JM (2018) Difficult-to-treat rheumatoid arthritis: an area of unmet clinical need. Rheumatology (Oxford) 57:1135–1144. https://doi.org/10.1093/rheumatology/kex349
Bécède M, Alasti F, Gessl I, Haupt L, Kerschbaumer A, Landesmann U, Loiskandl M, Supp GM, Smolen JS, Aletaha D (2019) Risk profiling for a refractory course of rheumatoid arthritis. Semin Arthritis Rheum 49:211–217. https://doi.org/10.1016/j.semarthrit.2019.02.004
Buch MH (2018) Defining refractory rheumatoid arthritis. Ann Rheum Dis 77:1705–1709. https://doi.org/10.1136/annrheumdis-2017-212862
Roodenrijs NMT, van der Goes MC, Welsing PMJ, Tekstra J, Lafeber F, Jacobs JWG, van Laar JM (2021) Difficult-to-treat rheumatoid arthritis: contributing factors and burden of disease. Rheumatology (Oxford) 60:3778–3788. https://doi.org/10.1093/rheumatology/keaa860
Hirano Y, Hasegawa J, Kosugiyama H, Kihira D, Hattori K (2021) Incidence rates of difficult-to-treat rheumatoid arthritis in real-world clinical practice. Ann Rheum Dis 80(Supplement 1):455. https://doi.org/10.1136/annrheumdis-2021-eular.1221
Takanashi S, Kaneko Y, Takeuchi T (2021) Characteristics of patients with difficult-to-treat rheumatoid arthritis in clinical practice. Rheumatology 60:5247–5256. https://doi.org/10.1093/rheumatology/keab209
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G et al (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581. https://doi.org/10.1002/art.27584
Nagy G, Roodenrijs NMT, Welsing PM, Kedves M, Hamar A, van der Goes MC et al (2021) EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 80:31–35. https://doi.org/10.1136/annrheumdis-2020-217344
England BR, Sayles H, Mikuls TR, Johnson DS, Michaud K (2015) Validation of the rheumatic disease comorbidity index. Arthritis Care Res 67:865–872. https://doi.org/10.1002/acr22456
Igarashi A, Akazawa M, Murata T, Taguchi T, Sadosky A, Ebata N, Willke R, Fujii K, Doherty J, Kobayashi M (2015) Cost-effectiveness analysis of pregabalin for treatment of chronic low back pain in patients with accompanying lower limb pain (neuropathic component) in Japan. Clinicoecon Outcomes Res 7:505–520. https://doi.org/10.2147/CEOR.S89833
Roodenrijs NMT, de Hair MJH, van der Goes MC, Jacobs JWG, Welsing PMJ, van der Heijde D et al (2018) Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey. Ann Rheum Dis 77:1705–1709. https://doi.org/10.1136/annrheumdis-2018-213687
Roodenrijs NMT, Hamar A, Kedves M, Nagy G, van Laar JM, van der Heijde D, Welsing PMJ (2021) Pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of difficult-to-treat rheumatoid arthritis. RMD Open 7:e001512. https://doi.org/10.1136/rmdopen-2020-00512
Takanashi S, Kaneko Y, Takeuchi T (2021) Elderly patients with comorbidities in the definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 80:1491–1493. https://doi.org/10.1136/annrheumdis-2021-220315
Ochi S, Sonomoto K, Nakayamada S, Tanaka Y (2022) Preferable outcome of Janus kinase inhibitors for a group of difficult-to-treat rheumatoid arthritis patients: from the FIRST Registry. Arthritis Res Ther 24:61. https://doi.org/10.1186/s13075-022-02744-7
Acknowledgements
Authors would like to thank Kaoru Kuwabara, Sayori Masuoka, Eri Morichika, and Aoi Yoshida for their dedicated data collection. The authors would also like to thank Enago (www.enago.jp) for the enthusiastic English language review.
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IY: conceptualization, part of methodology, software, validation, formal analysis, investigation, resources, data curation, writing—original draft, visualization, project administration. NS: recorded data, revised, gave suggestions, and approved manuscript. TC: recorded data, revised, gave suggestions, and approved manuscript.
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Ichiro Yoshii, Naoya Sawada, and Tatsumi Chijiwa declare that they have no conflict of interest. And their families have nothing to declare for this study. None of author and his families have share income, property with any person, or any grants or other financial supports of the study.
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This study was approved by our ethics committee (approval number: YH-RA-2021-3) in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. In addition, anonymity was ensured for all patients and families who participated in this study, and no names and/or addresses were issued that could help identify these individuals.
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Yoshii, I., Sawada, N. & Chijiwa, T. Clinical characteristics and variants that predict prognosis of difficult-to-treat rheumatoid arthritis. Rheumatol Int 42, 1947–1954 (2022). https://doi.org/10.1007/s00296-022-05124-1
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DOI: https://doi.org/10.1007/s00296-022-05124-1