Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD and Corticosteroids: A Multi-Center Randomized Controlled Trial in RA Patients with an Inadequate Response to Conventional Synthetic DMARDs, and New Therapy with Certolizumab Pegol

Abstract

Background: Treatment of rheumatoid arthritis (RA) includes the use of conventional (cs), biologic (b) disease-modifying anti-rheumatic drugs (DMARDs) and oral, intramuscularly, intravenous, or intraarticular (IA) glucocorticoids (GCs). In this paper, we analysed whether a treat-to-target (T2T) strategy optimizing csDMARD, oral, and IA-GC treatment as an adjunct new therapy to a new certolizumab pegol (CZP) therapy improves the effectivity in RA patients. Methods: 43 patients with active RA (≥6 tender, ≥6 swollen joints, ESR ≥ 20 mm/h or CRP ≥ 7mg/L) despite csDMARD treatment for ≥ 3 months and naïve to bDMARDs were randomized to CZP (200 mg/2 weeks after loading with 400 mg at weeks 0–2–4) plus a treat-to-target strategy (T2T, n = 21), or to CZP added to the established csDMARD therapy (fixed regimen, n = 22). The T2T strategy consisted of changing the baseline csDMARD therapy (1) SC-methotrexate (dose: 15 ≥ 20 ≥ 25 mg/week, depending on the initial dose) ≥ leflunomide (20 mg/d) ≥ sulphasalazine (2 × 1000 mg/d) plus (2) oral GCs (prednisolone 20–15–12.5–10–7.5–5–2.5–0 mg/d tapered every five days) and (3) injections of ≤5 affected joints with triamcinolone. DMARD modification and an addition of oral GCs were initiated, depending on the achievement of low disease activity (DAS 28 < 3.2). The primary objective was defined as the ACR 50 response at week 24. Results: ACR 50 was achieved in 76.2% of the T2T, as compared to 36.4% of the fixed regimen patients (p = 0.020). ACR 20 and 70 responses were achieved in 90.5% and 71.4% of the T2T patients and 59.1% and 27.3% of the fixed regimen patients, respectively (p = 0.045 and p = 0.010, respectively). The adverse event rate was similar for both groups (T2T n = 51; fixed regimen n = 55). Conclusion: Treat-to-target management with the optimization of csDMARDs, oral, and IA-GCs of RA patients in parallel to a newly established CZP treatment was safe and efficacious in comparison to a fixed regimen of csDMARDs background therapy.

Physician Adherence to Treat-to-Target and Practice Guidelines in Rheumatoid Arthritis

“…Recent studies have shown that T2T yields higher remission rates and improves quality of life over routine care [7]. Other reports also indicate that utilizing a T2T approach holds high potential also in patients with inadequate response to conventional synthetic disease modifying anti-rheumatic drugs (DMARDs), which remain fundamentals in the current treatment armamentarium [8,9]. These studies underscore the importance of applying T2T in a personalized approach of care, for which there may be signs of suboptimal application.…”

Rheumatoid Arthritis Treatment. A Back to the Drawing Board Project or High Expectations for Low Unmet Needs?

“…In this direction, the T2T strategy is the ideal approach. T2T therapy comprises fine principles: (a) the definition of a treatment target, (b) close monitoring and follow-up at predefined times to assess disease activity using composite measures, (c) regular treatment adjustment if the target is not achieved within a scheduled time, (d) consideration of patients’ individualized aspects, and (e) the shared decision making with the patient [14,33,34]. MTX is considered the “anchor”-drug among the csDMARDs.…”

How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy

“…Treatment targets should however be adapted according to the presence of comorbidities, individual patient factors and drug-associated risks [2] to ensure the most favorable benefit: risk ratio for any given patient. Treatment should be titrated to the therapeutic response assessed by composite measures of disease activity, ideally with therapy adjustment at least every three months [2] if the patient is not in remission, a recommendation based on evidence provided by clinical trials [13,14,15], until the desired treatment target is reached.…”