Updated Greek Rheumatology Society Guidelines for the Management of Rheumatoid Arthritis

Corresponding Author: Dimitrios Vassilopoulos, M.D. Professor of Medicine – Rheumatology Joint Rheumatology Program 2nd Department of Medicine and Laboratory National and Kapodistrian University of Athens School of Medicine Hippokration General Hospital 114 Vass. Sophias Ave. 115 27 Athens GREECE Tel.: +30-213-2088516 Fax: +30-213-2088399 e-mail: dvassilop@med.uoa.gr Mediterr J Rheumatol 2020;31(Supp 1):163-71


INTRODUCTION
The Greek Rheumatology Society and the Greek Association of Professional Rheumatologists (ERE-EPERE) has been issuing treatment Guidelines for rheumatoid arthritis (RA) since 2005. These Guidelines have been updated in 2009 and 2012. Here we present the updated Guidelines for the treatment of RA prepared by the Special Committee of Diagnostic and Therapeutic Protocols in Rheumatic Diseases of ERE-EPERE and input from experts in the field. In the preparation of these Guidelines the most recent Guidelines from the American College of Rheumatology (ACR) 1 , the Recommendations and Treat To Target paradigm from the European League against Rheumatism (EULAR) [2][3][4][5] were taken into account.

GENERAL PRINCIPLES OF THERAPY
Rheumatoid arthritis is the most common, chronic, autoimmune inflammatory arthritis in the Greek population that, without timely and effective treatment, leads to permanent joint or extra-articular damage, disability, impaired quality of life and decreased survival. The following General Principles apply to the treatment of RA in daily clinical practice: 1. RA is managed by the rheumatologist, and therapeutic choices are based on a shared decision process between the rheumatologist and the well-informed patient.
2. Treatment of RA should be initiated immediately after the diagnosis of the disease for better treatment outcomes and prevention of permanent joint damage.
3. Assessment of disease activity should be made with established indices of disease activity such as the Disease Activity Score (DAS) 28 -ESR, (Supplementary Table 1 Table 2).
5. To achieve the above therapeutic goals, frequent monitoring of patients every 1-3 months (for those with moderate/high disease activity) or 3-6 months (for those with low disease activity or in remission).
6. Treatment efficacy is assessed 3-6 months after treatment initiation or modification.
7. The criterion for changing or discontinuating treatment is the inability to achieve low disease activity (DAS28-ESR > 3.2).
8. Treatment decisions are based on disease activity, patients' preferences, presence or absence of adverse prognostic factors, presence of comorbidities and the occurrence of side effects from the administered therapies.

Therapeutic steps
The recommended 3 steps in the treatment of RA are shown in Figure 1. Most specifically: Step 1 1. The initial treatment step is the administration of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) as monotherapy: Α. The 1 st option is methotrexate (MTX) at a dose of 15-25 mg/week pos or subcutaneously in combination with folic acid (5 mg/week pos).
B. In patients with contraindications or intolerance/toxicity to MTX, leflunomide (LEF, 20 mg/day pos) should be administered next.
C. In patients with contraindications or intolerance/toxicity both to MTX and leflunomide, sulfasalazine (SSZ, up to 3 gm/day pos) or hydroxychloroquine (HCQ, 400 mg/day) are the next therapeutic options.
2. During treatment initiation or disease flares, glucocorticoids (prednisolone or its equivalent at a dose of ≤7.5 mg/day) may be added for a short period of time with rapid dose tapering (up to 6 months).
3. In patients with contraindications or intolerance/toxicity in the above csDMARDs, monotherapy with a biologic (bDMARD), or its approved biosimilar) or a targeted synthetic (ts)DMARD) is given:  Table 3) (RF or anti-CCP: +, DAS28 > 5.1, joint erosions), a bDMARD (or its approved biosimilar) or targeted synthetic(ts)DMARD is added:  4. In patients who fail the bio-original DMARDs, changing to their biosimilar is not recommended (or vice versa).

A. Biologic DMARDs (bDMARDs) Anti-Tumor Necrosis Factor -anti-TNFs
5. In patients with sustained complete remission of the disease (as defined by the ACR/EULAR criteria for remission, 6 Table 4) who are being treated with: A. csDMARD monotherapy: The following may be attempted: -a gradual csDMARD dose reduction, -and, only in exceptional cases, its discontinuation

B. Combination of a csDMARD and a bDMARD
The following may be attempted: -a gradual dose reduction or an increase in the administration interval of the bDMARD, or -a gradual csDMARD dose reduction

C. Monotherapy with a bDMARD
The following may be attempted: -a gradual dose reduction or increase in the administration interval of bDMARD 6. There are not adequate data so far to support the discontinuation of bDMARDs in patients with RA at remission.  (0-9.4) is an established index of disease activity of rheumatoid arthritis.