Clinical criteria for eligibility and maintenance of treatment with bDMARDs in 36 European countries with at least one biologic reimbursed
| Country | Major source of eligibility criteria | Who can prescribe bDMARDs to patients with RA | Requirement to start the first biologic | Time point for the first assessment of response (weeks) | Criteria to stop at 6 months* | Criteria to switch at 6 months* | Composite score for restrictiveness of clinical criteria (0–5) | ||
|---|---|---|---|---|---|---|---|---|---|
| Minimum disease duration | Level of disease activity | Number of sDMARDs to be failed, type of DMARD and length | |||||||
| Albania (no written source provided, criteria reported are those used in practice according to contact person) | REIM | Rheumatology | No requirement | DAS28>4.5 | 2 sDMARDs: MTX (20 mg/week) and SSZ (2.5 g/day) | NA | No criteria | No criteria | 2 |
| Austria24–26 | REIM=GUID | Rheumatology | No requirement | Moderate to high disease activity | 1 sDMARD: MTX in adequate dose and adequate duration | 12 | No criteria | Moderate disease activity | 4 |
| Belgium27 | REIM | Rheumatology | No requirement | DAS28>3.7 | 2 sDMARDs: MTX (15 mg/week)+another DMARD | 24 | DAS28>5.1 and improvement in DAS28 <1.2 OR DAS28 <5.1 and improvement in DAS28 <0.6 | No criteria | 2 |
| Bulgaria28 | REIM | Rheumatology | 6 months | DAS28>5.1 | 2 sDMARDs: MTX (20 mg/week) and LEFL (20 mg/day) for 6 months | 12 | No criteria | No criteria | 1 |
| Croatia29–31 | REIM=GUID | Rheumatology | 6 months | DAS28>5.1 AND HAQ 1.0–2.5 AND TJC>6 AND SJC>6 AND ESR>28 AND CRP>12 AND ACR I–III | 2 sDMARDs: MTX (20 mg/week)+another DMARD for 6 months | 12 | (DAS28>3.2 and improvement in DAS28 <1.2) OR improvement lower than ACR20 | No criteria | 1 |
| Cyprus32 | REIM=GUID | Rheumatology+Dermatology+Gastroenterology+Internal medicine | 6 months | DAS28>4 | 2 sDMARDs: MTX+another DMARD for at least 6 months | 12–16 | DAS28>3.2 and improvement in DAS28<1.2 | DAS28>3.2 and improvement <1.2 | 1 |
| Czech Republic33 34 | REIM=GUID | Rheumatology | 6 months | DAS28>3.9 | 1 sDMARD:, MTX (20 mg/week) OR LEFL (20 mg/day) OR SSZ (2 g/day) for 3–6 months | 12–16 | No criteria | Moderate disease activity | 2 |
| Denmark35 | GUID | Rheumatology | No requirement | DAS28>3.2 OR radiographic progression | 2 sDMARDs: MTX (25 mg/week) and SSF (2 g/day) | 12–16 | No criteria | No criteria | 3 |
| Estonia36 37 | REIM+GUID | Rheumatology | 6 months | DAS28>4.6 AND TJC>8 AND SJC>6 AND morning stiffness>1 h AND ESR 30 AND CRP 25 mg/L AND active visceral disease by expert opinion | 4 sDMARDs: including MTX (25 mg/week) and Prednisone (7.5 mg/week) | 12–24 | Improvement in DAS28<1.2 | DAS28>4.6 AND TJC>8 AND SJC>6 AND morning stiffness>1 h AND ESR 30 AND CRP 25 mg/L AND active visceral disease by expert opinion | 0 |
| Finland38 | REIM | Rheumatology+Internal medicine | No requirement | Active disease | 3 sDMARDs | NA | No criteria | No criteria | 2 |
| France39 | GUID | Rheumatology+Internal medicine | No requirement | DAS28>5.1 OR lower if corticodependence or structural damage progression | None to 1 sDMARD: for the majority of biologics, only MTX is mentioned without any strict dose or regimen | 12 | No criteria | No criteria | 3 |
| Germany40 | REIM+GUID | Rheumatology+Dermatology+Gastroenterology+Internal medicine+GP+other specialties | No requirement (min. 3 months recommended) | No requirement | No requirement (2 sDMARDs: including MTX, LEF, SSZ, HCQ, Gold and CyA recommended) | 12 | No criteria | No criteria | 5 |
| Greece40a | REIM+GUID | Rheumatology | No requirement | DAS28>5.1 or DAS28>3.2 AND presence of adverse prognostic factors * (≥2/5) *Adverse prognostic factors: RF/anti-CCP, joint erosions in X-ray, HAQ>1, large joint involvement and extra-articular disease | 1. In established RA: 2 sDMARD either MTX (≥15 mg/week) or LEFL (20 mg/day) or 1 sDMARD if adverse prognostic factors* (≥2/5) 2. In early RA anti-TNF agents are allowed (combined to MTX) as the first therapy in case of highly active disease (DAS28>5.1) AND presence of adverse prognostic factors* (>2/5) | 12 | DAS28>3.2 | DAS28>3.2 | 2 |
| Hungary42 43 | REIM+GUID | Rheumatology | 3 months | DAS28>5.1 | 2 sDMARDs: MTX and another sDMARD in ‘full dose or tolerable dose’ | 12 | Improvement DAS28 <1.2 | Improvement in DAS28 <1.2 | 1 |
| Iceland41 | REIM+GUID | Rheumatology+Dermatology+Gastroenterology | No requirement | DAS28 3.2 (progressing radiographic damage facilitates initiation of biologics) | 1 sDMARD: MTX (20 mg/week) | 24 | No criteria | DAS28>3.2 | 4 |
| Ireland44 | GUID | Rheumatology+Dermatology+Gastroenterology+Internal medicine+other specialties | No requirement | No requirement | 1 sDMARD: MTX (25 mg/week) for 3 months | 12 | No criteria | No criteria | 5 |
| Italy45 | GUID | Rheumatology+Dermatology+Gastroenterology | 3 months | DAS28>3.2 | 1 sDMARD: MTX (15 mg/week) for 3 months | NA | No criteria | No criteria | 3 |
| Latvia46 | REIM | Rheumatology | No requirement | DAS28>3.2 | 3 sDMARDs: MTX (20 mg/week)+another 2 DMARDs for 3–6 months | 12 | No criteria | DAS28>3.2 | 2 |
| Lithuania47–49 | REIM=GUID | Rheumatology | No requirement | DAS28>5.1 | 2 sDMARDs: choice MTX (25 mg/week) for 3 months, AZATH (100 mg/day) for 3 months, LEFL (20 mg/day) for 3 months, HCQ (400 mg/day) for 3 months and SSZ (2 g/day) for 6 months | 12 | Improvement in DAS28 <1.2 after 3 months | Improvement in DAS28 <1.2 after 3 months | 2 |
| Luxemburg | No regulation in access to reimbursed biologics | Rheumatology+Dermatology+Gastroenterology+Internal medicine+GP+other specialties | No requirement | No requirement | No requirement | NA | No criteria | No criteria | 5 |
| Macedonia50 | REIM | Rheumatology | No requirement | DAS28>4.2 AND SJC>=6 | 2 sDMARDs for 6 months | 6–12 | No criteria | No criteria | 2 |
| Malta51 | REIM | Rheumatology | 6 months | No requirement | 2 sDMARDs: choice MTX for 6 months (at least 2 months on 15 mg/week), LEFL (20 mg/day) for months and SSZ (2 g/day) | 12 | DAS28>3.2 and improvement in DAS28 <1.2 | No criteria | 3 |
| Montenegro52 | REIM | Rheumatology | 6 months | DAS≥5.1 AND HAQ between 1 and 2.5 AND ACR I–III AND increased ESR and CRP AND SJC≥6 AND Painful joints ≥6 | 2 sDMARDs: choice MTX (20 mg/week), SSZ (2 g/day) and LEFL(20 mg/day) for 3 months each | NA | No criteria | Improvement in DAS28 <1.2 | 1 |
| The Netherlands53 | REIM+GUID | Rheumatology | No requirement | DAS28>3.2 | 2 sDMARDs: MTX and another sDMARD | NA | Improvement in DAS28 <1.2 | Improvement in DAS28 <1.2 | 3 |
| Norway54 | REIM=GUID | Rheumatology | No requirement | DAS28≥3.2 | 1 sDMARD | 12–24 | No criteria | No criteria | 4 |
| Poland55 | REIM | Rheumatology | 12 months | DAS28>5.1 OR DAS>3.7 if joints of lower limbs are involved | 2 sDMARDs: MTX (25 mg/week) for at least 3 months+another DMARD | 9 | Improvement in DAS28<1.2 in 90 days | Improvement in DAS28 <1.2 in 90 days | 1 |
| Portugal56 | REIM+GUID | Rheumatology+Internal medicine | No requirement | DAS>3.2 OR 2.6<DAS <3.2 AND (worsening of HAQ>0.22 (6/6M) OR worsening of X-ray scores: Larsen>6/SvdH>5 (12/12M)) | 1 sDMARD: MTX in conventional dose for 3 months or another DMARD for 6 months | 12 | Improvement in DAS28<1.2 OR Improvement in DAS28<0.6 in 3 months | Improvement in DAS28<1.2 OR <0.6 in 3 months | 4 |
| Romania57 | REIM+GUID | Rheumatology | No requirement | DAS28>5.1, including minimum five joints with active synovitis AND at least two of the following: morning stiffness>60 min AND ESR 1 h>28 OR CRP>20 mg/mL | 2 sDMARDs: choice MTX (20 mg/week), SSZ (3 g/day) and LEFL (20 mg/day) for 12 weeks each | 24 | No criteria | DAS28 is stable≥5.1 or improvement in DAS28 <1.2 between two separate evaluations | 2 |
| Serbia58 59 | REIM+GUID | Rheumatology | 6 months | Immediate and high activity (ACR I–III/DAS28>5.1 AND HAQ 1–2.5), high evolution | 2 sDMARDs: MTX (7.5 mg/week) for at least 6 months AND choice: PRED (7.5 mg/day) at least 1 month or SSZ (500 mg/day) at least 1 month | 12–16 | No criteria | Improvement in DAS28 <1.2 | 1 |
| Slovakia60 | GUID | Rheumatology | 6 months | Moderate to high disease activity | 1 sDMARD: MTX (15 mg/week) for 3 months | 12 | No criteria | Moderate disease activity | 3 |
| Slovenia61 | REIM=GUID | Rheumatology | No requirement | DAS28>4.2 AND SJC>=8 | 2 sDMARDs: MTX (20 mg/week) and choice LEFL (20 mg/day) or SSZ (2 g/day) | 24 | Improvement in DAS28<1.2 | No criteria | 2 |
| Spain62 62a | GUID | Rheumatology | No requirement | DAS28≥3.2 OR SDAI≥11OR [(DAS28 between 2.6 - 3.2 OR SDAI 5-11) AND (persistent inflammation in joints considered important for the patient that does not resolve with local therapies or significant radiographic progression)] | 1 sDMARD: MTX (25 mg/week) | 12 | No criteria | DAS28≥3.2 OR SDAI≥11OR [(DAS28 between 2.6 - 3.2 OR SDAI 5-11) AND (persistent inflammation in joints considered important for the patient that does not resolve with local therapies or significant radiographic progression)] | 4 |
| Sweden63 64 | GUID | Rheumatology+Dermatology+Gastroenterology+Internal medicine+GP+other specialties | No requirement | DAS28>3.2 and several negative prognostic factors OR DAS28>5.1 | No requirement | 12 | No criteria | DAS28>3.2 and several negative prognostic factors | 3 |
| Switzerland65–67 | REIM | Rheumatology+Dermatology+Gastroenterology+Internal medicine+GP | No requirement | No requirement | 1 sDMARD | NA | No criteria | No criteria | 5 |
| Turkey68 | REIM | Rheumatology+other specialties | No requirement | DAS28>5.1 | 3 sDMARDs, including MTX | 12 | Improvement in DAS28 <1.2 OR improvement in DAS28 <0.6 in 3 months | No criteria | 1 |
| UK69 70 | REIM | Rheumatology | 6 months | DAS28>5.1 | 2 sDMARDs, including MTX | 26 | Improvement in DAS28<1.2 | Improvement in DAS28 <1.2 | 1 |
*When criteria at different time points were defined, these are also added in the table with the corresponding information on the respective time point.
ACR, American College of Rheumatology; Anti-CCP, cyclic citrullinated peptide; AZATH, azathioprine; CRP, C reactive protein; Cya, cyclosporine; DAS28, disease activity score with 28-joint assessment; DMARD, disease-modifying anti-rheumatic drugs; ESR, erythrocyte sedimentation rate; GP, general practitioner; GUID, national guideline; HAQ, Health Assessment Questionnaire; HCQ, hydroxychloroquine; LEFL, leflunomide; MTX, methotrexate; PRED, prednisolone; RA, rheumatoid arthritis; REIM, reimbursement criteria; RF, rheumatoid factor; SDAI, Simple Disease Activity Index; sDMARD, synthetic disease-modifying antirheumatic drugs; SJC, swollen joint count; SSZ, sulfasalazine; TJC, total joint count; TNF, tumour necrosis factor.