Loading...
 

Volume 34, Issue 4, December 2023



Sign in to download the Issue in PDF format.

Mediterr J Rheumatol 2020;31(Supp 1):163-71
Updated Greek Rheumatology Society Guidelines for the Management of Rheumatoid Arthritis
Authors Information
1. Joint Rheumatology Program, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, Hippokration General Hospital, Athens, Greece
2. Private Practice, Thessaloniki, Greece
3. Joint Rheumatology Program, 4th Department of Medicine, National and Kapodistrian University of Athens, School of Medicine, Attikon University General Hospital, Athens, Greece
4. Hygeia Hospital, Athens, Greece
5. Private Practice, Ioannina, Greece
6. Metropolitan Hospital, Piraeus, Greece
7. Joint Rheumatology Program, 1st Dept of Propaedeutic & Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, Laiko General Hospital, Athens, Greece
8. Clinical Immunology and Allergy Department, Medical School, University of Crete, Heraklion, Greece
Abstract
This paper has no abstract.

https://doi.org/10.31138/mjr.31.1.163

This work is licensed under a Creative Commons Attribution 4.0 International License (CC-BY).

©Vassilopoulos D, Aslanidis S, Boumpas D, Kitas GD, Nikas SN, Patrikos D, Sfikakis PP, Sidiropoulos P.

Full Text

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)2-5 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.

 

  1. Treatment of RA should be initiated immediately after the diagnosis of the disease for better treatment outcomes and prevention of permanent joint damage.

 

  1. 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).

 

  1. Treatment targets include sustained remission (DAS28-ESR < 2.6) or, if this is not possible, low disease activity (DAS28-ESR < 3.2) for all RA patients (Supplementary Table 2).

 

  1. 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).

 

  1. Treatment efficacy is assessed 3-6 months after initiation or modification of therapies.

 

  1. The criterion for changing or discontinuation of treatment is the inability to achieve low disease activity (DAS28-ESR > 3.2).

 

  1. Treatment decisions are based on disease activitypatients’ preferences, presence or absence of adverse prognostic factorspresence 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:

 

a. The 1st 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:

A. Biologic DMARDs (bDMARDs)

Anti-Tumour Necrosis Factors - anti-TNFs (in alphabetic order)

                           Adalimumab

                           Certolizumab Pegol

                           Etanercept

                           Golimumab

                           Infliximab

                                   or

Non-anti-TNFs

                           Abatacept

                           IL-6 inhibitors (Tocilizumabor Sarilumab-EMA approved)

                           IL-1 inhibitors (Anakinra)

                                 or

EMA-approved biosimilars

 

B. Janus Kinase (JAK) inhibitor

                                 Τofacitinib

                                 Βaricitinib (EMA approved)

                                 Upadacitinib (EMA approved)

                                or

 

C. Rituximab: Only in patients with history of:

            - Lymphoproliferative diseases or

            - Demyelinating diseases or

            - Solid organ neoplasias

 

Step 2

1. In patients who fail csDMARD monotherapy and in the:

A. Absence of adverse prognostic factors

(RF and anti-CCP: - and DAS28: 3.2-5.1 and absence of joint erosions),

 

a. Switching to or

               b. Addition of

a 2nd csDMARD (MTX, LEF, SSZ, HCQ) is recommended

 

B. Presence of ≥1 adverse prognostic factors (Supplementary Table 3)

(RF or anti-CCP: +, DAS28 > 5.1, joint erosions),

a bDMARD (or its approved biosimilar) or tsDMARD is added:

 

A. Biologic DMARDs (bDMARDs)

Anti-Tumor Necrosis Factors - anti-TNFs (in alphabetic order)

                           Adalimumab

                           Certolizumab Pegol

                           Etanercept

                           Golimumab

                           Infliximab

                                   or

Non-anti-TNFs

                           Abatacept

                           IL-6 inhibitors (Tocilizumabor Sarilumab-EMA approved)

                           IL-1 inhibitors (Anakinra)

                                 or

EMA-approved biosimilars

 

B. JAK Inhibitor

                                 Τofacitinib

                                 Βaricitinib (EMA approved)

                                 Upadacitinib (EMA approved)

 

                                or

C. Rituximab: Only in patients with history of:

            - Lymphoproliferative diseases or

            - Demyelinating diseases or

            - Solid organ neoplasias

 

 

Step 3

1. In patients who had failed ≥2 or combination of csDMARDs, a bDMARD (or its approved biosimilar) or tsDMARD is added:

A. Biologic DMARDs (bDMARDs)

Anti-Tumor Necrosis Factors - anti-TNFs (in alphabetic order)

                           Adalimumab

                           Certolizumab Pegol

                           Etanercept

                           Golimumab

                           Infliximab

                                   or

Non-anti-TNFs

                           Abatacept

                           IL-6 inhibitors (Tocilizumabor Sarilumab-EMA approved)

                           IL-1 inhibitors (Anakinra)

                                 or

Their EMA-approved biosimilars

 

B. 1st JAK Inhibitor

                                 Τofacitinib

                                 Βaricitinib (EMA approved)

                                 Upadacitinib (EMA approved)

                                or

C. Rituximab: Only in patients with history of:

            - Lymphoproliferative diseases or

            - Demyelinating diseases or

            - Solid organ neoplasias

 

2. In patients who had failed their 1st bDMARD, a 2nd bDMARD (or its approved biosimilar) or a tsDMARD can be added:

A. 2nd bDMARD:

            Anti-Tumor Necrosis Factors - anti-TNFs (in alphabetic order)

                           Adalimumab

                           Certolizumab Pegol

                           Etanercept

                           Golimumab

                           Infliximab

                                   or

Non-anti-TNFs

                           Abatacept

                           IL-6 inhibitors (Tocilizumabor Sarilumab-EMA approved)

                           IL-1 inhibitors (Anakinra)

                                 or

EMA-approved biosimilars

 

B. 1st JAK inhibitor

                                 Τofacitinib

                                 Βaricitinib (EMA approved)

                                 Upadacitinib (EMA approved)

 

3. In patients who had failed the 1st JAK Inhibitor, a 2nd bDMARD (or its approved biosimilar) or a 2nd tsDMARD, can be added:

 

A. Anti-TNFs (in alphabetical order)

                           Adalimumab

                           Certolizumab Pegol

                           Etanercept

                           Golimumab

                           Infliximab

                                  or

Non-anti-TNF

                           Abatacept

                           IL-6 Inhibitor (Tocilizumab or Sarilumab)

                           Anakinra

                           Rituximab (after failure of anti-TNF)

                                 or

EMA-approved biosimilars

 

B. 2nd JAK inhibitor

                                 Τofacitinib

                                 Βaricitinib (EMA approved)

                                 Upadacitinib (EMA approved)

 

Special Considerations

1. The dose of MTX should be gradually increased up to 20-25 mg/week to achieve the therapeutic target. At doses greater than 15 mg/week, subcutaneous administration of the drug is preferred.

 

2. In patients with contraindications, intolerance or toxicity to csDMARDs, administration as monotherapy of biological agents is indicated (anti-TNFs: Αdalimumab, Certolizumab pegol, Etanercept, anti-IL6: Tocilizumab, Sarilumab) or their EMA-approved biosimilars and JAK inhibitors (Tofacitinib, Baricitinib, Upadacitinib). More efficacy data regarding monotherapies are available for IL-6 and JAK inhibitors.

 

3. Among bDMARDs, Anakinra appears to have limited efficacy compared to other bDMARDs (anti-TNFs and non-anti-TNFs).

 

4. In patients who fail the bio-original DMARDs, changing to their biosimilar is not recommended (or vice versa).

 

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.

 

7. The recommended doses of the different DMARDs are shown in Supplementary Tables 4-6.

 

Figure 1. Therapeutic algorithm of rheumatoid arthritis.
 


CONCLUSIONS

These Guidelines propose a 3-step approach to the treatment of RA targeting low disease activity (DAS28-ESR < 3.2) and always take into consideration the presence or absence of adverse prognostic factors, the presence of comorbidities, and the development of side effects during therapy. Therapeutic decisions should be the result of a shared decision process between the rheumatologist and the well-informed patient.

Supplementary Table 1. DAS28-ESR.
 


Supplementary Table 2. Disease activity categories according to DAS28-ESR score.
 


Supplementary Table 3. Adverse prognostic factors.
 


Supplementary Table 4. ACR/EULAR definitions of remission in rheumatoid arthritis.
 


 


Supplementary Table 6. Recommended doses of JAK inhibitors.
 

References
  1. Singh JA, Saag KG, Bridges SL Jr., Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol 2016;68:1-26.
  2. Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960-77.
  3. Kay J, Schoels MM, Dorner T, Emery P, Kvien TK, Smolen JS, et al. Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases. Ann Rheum Dis 2018 Feb;77(2):165-74.
  4. Combe B, Landewe R, Daien CI, Hua C, Aletaha D, Álvaro-Gracia JM, et al. 2016 update of the EULAR recommendations for the management of early arthritis. Ann Rheum Dis 2017;76:948-59.
  5. Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis 2016;75:3-15.
  6. Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J, et al. American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis 2011;70:404-13.