title: Treating to target in established rheumatoid arthritis: Challenges and opportunities in an era of novel targeted therapies and biosimilars.
abstract: There is increasing consensus that periodic monitoring of disease activity status in rheumatoid arthritis (RA) patients to achieve and maintain remission, or at least low disease activity (LDA), the so-called treat to target (T2T) improves outcomes regardless of the duration of disease. Based on systematic literature reviews (SLRs) of clinical trials and registries, International Recommendations published in 2015 represent expert opinion describing efficacy and safety of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs). A total of 10 recommendations are detailed from four "Overarching Principles": (1) treatment decisions are shared between patient and rheumatologist; (2) the primary goalv is to maximize long-term quality of life by controlling the symptoms, preventing joint damage, and by normalizing the function and social and work participation; (3) abrogation (not just control) of inflammation is the most effective method to achieve this goal; (4) T2T by measuring disease activity regularly and adjusting therapy to achieve remission/LDA optimizes outcomes in RA. The SLRs provide solid evidence that methotrexate is the "anchor" of csDMARD and that step-up therapy by adding/substituting other csDMARDs, such as sulfasalazine (SSZ), hydroxychloroquine (HCQ), or/and leflunomide (LEF) is as effective as combination therapy to initiate. Tofacitinib, a recently marketed csDMARD, may be more effective in comparison to MTX, and can be used in combination. Rapid disease control can be achieved by "bridging" with various regimens of glucocorticoids (GCs), but tapering to doses ≤7.5 mg/day is critical to limit side effects. In practice settings, use of bDMARDs is influenced by reimbursement. Tumor necrosis factor inhibitors (TNFi) are highly used, but as more data emerge, there appear to be no major differences to more recently available targeted bDMARD monoclonal antibodies such as abatacept (co-stimulation blockade), rituximab (B cell depleting), tocilizumab (TCZ) (interleukin (IL)-6 receptor blockade). Rituximab appears to be most effective for seropositive patients, and tocilizumab may be more effective as a monotherapy in patients intolerant to csDMARDs. Besides T2T, attention to managing treatment and optimizing outcomes should take into account potential adverse effects, such as risk of serious infection, as well as potential morbidity/mortality related to cardiovascular events, pulmonary disease, osteoporosis, diabetes, and fibromyalgia which often influence some measures, such as the Health Assessment Questionnaire (HAQ).
authors.affiliation: Division of Rheumatology, David Geffen School of Medicine, University of California (UCLA), Los Angeles, USA. Electronic address: thasia@woodworth.info.
authors.forename: Thasia G
authors.initials: TG
authors.lastname: Woodworth
authors.affiliation: Dept. of Rheumatology, Sint Maartenskliniek, PO Box 9011, 6500 GM, Nijmegen, The Netherlands.
authors.forename: Alfons A
authors.initials: AA
authors.lastname: den Broeder
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000523:psychology; D001685:Biological Factors / Q000627:therapeutic use; D059451:Biosimilar Pharmaceuticals / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008727:Methotrexate / Q000627:therapeutic use; D011788:Quality of Life / Q000523:psychology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001685:Biological Factors; D059451:Biosimilar Pharmaceuticals; D005938:Glucocorticoids; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept; D000077339:Leflunomide; C502936:tocilizumab; D008727:Methotrexate
keywords: Biologics and biosimilars; Disease activity; Disease modifying antirheumatic drugs; Remission; Rheumatoid arthritis; Treat-to-target