From basic therapy to genetically engineered biological drugs: Predicting response in a cohort of patients with rheumatoid arthritis not meeting D2TRA criteria
Abstract. Rheumatoid arthritis (RA) is a systemic autoimmune disease in which, in some patients, standard therapy, primarily by methotrexate, is ineffective or poorly tolerated, necessitating the use of genetically engineered biological drugs (GIBDs). However, the characteristics of patients receiving GIBD or targeted synthetic basic anti inflammatory agents (tsBAIAs) without meeting the criteria for difficult-to-treat RA (D2TRA) are still remaining poorly studied.A.I. Zagrebneva, E.N. Simonova, Yu.A. Gavrikova, V.V. Dolgov, A.A. Buyanova, O.D. Dukhanina, E.L. Isakulyan, R.R. Samigullina, V.I. Mazurov
The aim: to compare the characteristics of RA patients being on basic therapy with those switched to GIBDs/tsBAIAs without D2TRA criteria, and identify predictors of GIBDs/tsBAIAs switching.
Material and methods. The study included 198 patients with RA: the basic therapy group (n = 99) and “GIBDs/tsBAIAs, not D2TRA” group (n = 99). All the participants were estimated for demographic, clinical, laboratory, instrumental, and psychometric parameters. Logistic regression and ensemble models (RandomForest, XGBoost) were used to identify the studied predictors. The duration of treatment retention was analyzed using Kaplan – Meier curves and a Cox regression model.
Results. Patients receiving biologic agents/tsBAIAs had a longer RA duration, more severe structural joint damage, worse functional status, and signs of systemic vascular involvement. Logistic model demonstrated high predictive power (AUC = 0.909). Key predictors of switching to GIBDs/tsBAIAs included disability group 3, elevated urine leukocytes level, elevated CAVI index, increased left ventricular end-diastolic diameter, decreased stroke volume, lower anankastia values according to the PID-5-BF scale, and a low B1-globulin percentage. No differences in treatment duration were found between GIBDs lines or classes (p >0.3). Adverse events in the previous line of therapy were not associated with their development later.
Conclusion. Patients without D2TRA criteria who are being switched to GIBDs/tsBAIAs represent a heterogeneous group of patients with a more severe and systemic course of RA. The identified predictors of switching to GIBDs/tsBAIAs can be used for early identification of patients at high risk of failure of basic therapy and optimization of treatment strategies.
Keywords
rheumatoid arthritis
basic therapy for rheumatoid arthritis
methotrexate
genetically engineered biological drugs
targeted synthetic anti-inflammatory drugs
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About the Authors
Alena I. Zagrebneva, MD, PhD (Medicine), physician of the highest qualification category; chief external expert – rheumatologist, Department of Healthcare of Moscow; head of Moscow City Scientific and Practical Center for Immune-Inflammatory Rheumatic Diseases and Autoimmune Inflammatory Diseases, Moscow Clinical Research Center Hospital No. 52; associate professor of the Department of therapy and rheumatology named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University, Moscow, Russian Federation.E-mail: alrheumo@mail.ru
ORCID: https://orcid.org/0000-0002-3235-1425. eLibrary SPIN: 6351-4980
Elena N. Simonova, MD, head of Consultative and Diagnostic Center No. 2, Moscow Scientific and Practical Center for Systemic Immune-Inflammatory Rheumatic Diseases and Autoinflammatory Diseases, Moscow Clinical Research Center Hospital No. 52, Moscow, Russian Federation.
E-mail: 4130524@mail.ru
ORCID: https://orcid.org/0000-0002-8372-6995
Yulia A. Gavrikova, MD, rheumatologist of Consultative and Diagnostic Center No. 2, Moscow Scientific and Practical Center for Systemic Immune-Inflammatory Rheumatic Diseases and Autoinflammatory Diseases, Moscow Clinical Research Center Hospital No. 52; specialist of organizational and methodological department on rheumatology, Research Institute of healthcare and Medical Management Organization, Moscow, Russian Federation.
E-mail: jgavrikovagkb52@gmail.com
ORCID: https://orcid.org/0000-0001-8414-1545
Vladislav V. Dolgov, MD, rheumatologist of Consultative and Diagnostic Center No. 2, Moscow Scientific and Practical Center for Systemic Immune-Inflammatory Rheumatic Diseases and Autoinflammatory Diseases, Moscow Clinical Research Center Hospital No. 52; specialist of organizational and methodological department on rheumatology, Research Institute of healthcare and Medical Management Organization, Moscow, Russian Federation.
E-mail: drdolgovvv@gmail.com
ORCID: https://orcid.org/0000-0001-8007-5499
Anastasia A. Buyanova, MD, a doctor of Consultative and Diagnostic Center No. 2, Moscow Scientific and Practical Center for Systemic Immune-Inflammatory Rheumatic Diseases and Autoinflammatory Diseases, Moscow Clinical Research Center Hospital No. 52, Moscow, Russian Federation.
E-mail: anastasiiabuianova97@gmail.com
ORCID: https://orcid.org/0000-0001-7894-9222. Scopus ID: 57218589485. eLibrary SPIN: 5725-7792
Olga D. Dukhanina, MD, clinical pharmacologist of the Department of clinical pharmacology, Moscow Clinical Research Center Hospital No. 52; analyst at the Department of scientific activity coordination, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation.
E-mail: Konovaolly@mail.ru
ORCID: https://orcid.org/0000-0002-0125-4606
Elizaveta L. Isakulyan, MD, junior researcher at the Department of suicidology, Z.P. Solovyov Scientific and Practical Psychoneurological Center; psychiatrist at Moscow Clinical Research Center Hospital No. 52, Moscow, Russian Federation.
E-mail: liza-78953@mail.ru
ORCID: https://orcid.org/0009-0000-0446-9699
Ruzana R. Samigullina, MD, PhD (Medicine), assistant at the Department of therapy and rheumatology named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University; rheumatologist; head of the City Center for Therapy with Genetically Engineered Biological Drugs, V.A. Nasonova Saint Petersburg Clinical Rheumatological Hospital No. 25, Saint Petersburg, Russian Federation.
E-mail: dr.samigullina@yandex.ru
ORCID: https://orcid.org/0000-0002-6341-3334
Vadim I. Mazurov, MD, Dr. Sci. (Medicine), professor, academician of RAS, Honored Scientist of the Russian Federation, chief scientific advisor, director of the Rheumatology research institute, head of the Department of therapy and rheumatology named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University; head of the Center for Autoimmune Diseases, V.A. Nasonova Saint Petersburg Clinical Rheumatological Hospital No. 25, Saint Petersburg, Russian Federation.
E-mail: maz.nwgmu@yandex.ru
ORCID: https://orcid.org/0000-0002-0797-2051
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