Table 1

Clinical criteria for eligibility and maintenance of treatment with bDMARDs in 36 European countries with at least one biologic reimbursed

CountryMajor source of eligibility criteriaWho can prescribe bDMARDs to patients with RARequirement to start the first biologicTime 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 durationLevel of disease activityNumber 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)REIMRheumatologyNo requirementDAS28>4.52 sDMARDs: MTX (20 mg/week) and SSZ (2.5 g/day)NANo criteriaNo criteria2
Austria24–26REIM=GUIDRheumatologyNo requirementModerate to high disease activity1 sDMARD: MTX in adequate dose and adequate duration12No criteriaModerate disease activity4
Belgium27REIMRheumatologyNo requirementDAS28>3.72 sDMARDs: MTX (15 mg/week)+another DMARD24DAS28>5.1 and improvement in DAS28 <1.2
OR
DAS28 <5.1 and improvement in DAS28 <0.6
No criteria2
Bulgaria28REIMRheumatology6 monthsDAS28>5.12 sDMARDs: MTX (20 mg/week) and LEFL (20 mg/day) for 6 months12No criteriaNo criteria1
Croatia29–31REIM=GUIDRheumatology6 monthsDAS28>5.1 AND HAQ 1.0–2.5 AND TJC>6 AND SJC>6 AND ESR>28 AND CRP>12 AND ACR I–III2 sDMARDs: MTX (20 mg/week)+another DMARD for 6 months12(DAS28>3.2 and improvement in DAS28 <1.2)
OR improvement lower than ACR20
No criteria1
Cyprus32REIM=GUIDRheumatology+Dermatology+Gastroenterology+Internal medicine6 monthsDAS28>42 sDMARDs: MTX+another DMARD for at least 6 months12–16DAS28>3.2 and improvement in DAS28<1.2DAS28>3.2 and improvement <1.21
Czech Republic33 34REIM=GUIDRheumatology6 monthsDAS28>3.91 sDMARD:, MTX (20 mg/week) OR LEFL (20 mg/day) OR SSZ (2 g/day) for 3–6 months12–16No criteriaModerate disease activity2
Denmark35GUIDRheumatologyNo requirementDAS28>3.2 OR radiographic progression2 sDMARDs: MTX (25 mg/week) and SSF (2 g/day)12–16No criteriaNo criteria3
Estonia36 37REIM+GUIDRheumatology6 monthsDAS28>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 opinion4 sDMARDs: including MTX (25 mg/week) and Prednisone (7.5 mg/week)12–24Improvement in DAS28<1.2DAS28>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 opinion0
Finland38REIMRheumatology+Internal medicineNo requirementActive disease3 sDMARDsNANo criteriaNo criteria2
France39GUIDRheumatology+Internal medicineNo requirementDAS28>5.1 OR lower if corticodependence or structural damage progressionNone to 1 sDMARD: for the majority of biologics, only MTX is mentioned without any strict dose or regimen12No criteriaNo criteria3
Germany40REIM+GUIDRheumatology+Dermatology+Gastroenterology+Internal medicine+GP+other specialtiesNo requirement (min. 3 months recommended)No requirementNo requirement (2 sDMARDs: including MTX, LEF, SSZ, HCQ, Gold and CyA recommended)12No criteriaNo criteria5
Greece40aREIM+GUIDRheumatologyNo requirementDAS28>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)
12DAS28>3.2DAS28>3.22
Hungary42 43REIM+GUIDRheumatology3 monthsDAS28>5.12 sDMARDs: MTX and another sDMARD in ‘full dose or tolerable dose’12Improvement DAS28 <1.2Improvement in DAS28 <1.21
Iceland41REIM+GUIDRheumatology+Dermatology+GastroenterologyNo requirementDAS28 3.2 (progressing radiographic damage facilitates initiation of biologics)1 sDMARD: MTX (20 mg/week)24No criteriaDAS28>3.24
Ireland44GUIDRheumatology+Dermatology+Gastroenterology+Internal medicine+other specialtiesNo requirementNo requirement1 sDMARD: MTX (25 mg/week) for 3 months12No criteriaNo criteria5
Italy45GUIDRheumatology+Dermatology+Gastroenterology3 monthsDAS28>3.21 sDMARD: MTX (15 mg/week) for 3 monthsNANo criteriaNo criteria3
Latvia46REIMRheumatologyNo requirementDAS28>3.23 sDMARDs: MTX (20 mg/week)+another 2 DMARDs for 3–6 months12No criteriaDAS28>3.22
Lithuania47–49REIM=GUIDRheumatologyNo requirementDAS28>5.12 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 months12Improvement in DAS28 <1.2 after 3 monthsImprovement in DAS28 <1.2 after 3 months2
LuxemburgNo regulation in access to reimbursed biologicsRheumatology+Dermatology+Gastroenterology+Internal medicine+GP+other specialtiesNo requirementNo requirementNo requirementNANo criteriaNo criteria5
Macedonia50REIMRheumatologyNo requirementDAS28>4.2 AND SJC>=62 sDMARDs for 6 months6–12No criteriaNo criteria2
Malta51REIMRheumatology6 monthsNo requirement2 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)12DAS28>3.2 and improvement in DAS28 <1.2No criteria3
Montenegro52REIMRheumatology6 monthsDAS≥5.1 AND HAQ between 1 and 2.5 AND ACR I–III AND increased ESR and CRP AND SJC≥6 AND Painful joints ≥62 sDMARDs: choice MTX (20 mg/week), SSZ (2 g/day) and LEFL(20 mg/day) for 3 months eachNANo criteriaImprovement in DAS28 <1.21
The Netherlands53REIM+GUIDRheumatologyNo requirementDAS28>3.22 sDMARDs: MTX and another sDMARDNAImprovement in DAS28 <1.2Improvement in DAS28 <1.23
Norway54REIM=GUIDRheumatologyNo requirementDAS28≥3.21 sDMARD12–24No criteriaNo criteria4
Poland55REIMRheumatology12 monthsDAS28>5.1 OR DAS>3.7 if joints of lower limbs are involved2 sDMARDs: MTX (25 mg/week) for at least 3 months+another DMARD9Improvement in DAS28<1.2 in 90 daysImprovement in DAS28 <1.2 in 90 days1
Portugal56REIM+GUIDRheumatology+Internal medicineNo requirementDAS>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 months12Improvement 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
Romania57REIM+GUIDRheumatologyNo requirementDAS28>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/mL2 sDMARDs: choice MTX (20 mg/week), SSZ (3 g/day) and LEFL (20 mg/day) for 12 weeks each24No criteriaDAS28 is stable≥5.1 or improvement in DAS28 <1.2 between two separate evaluations2
Serbia58 59REIM+GUIDRheumatology6 monthsImmediate and high activity (ACR I–III/DAS28>5.1 AND HAQ 1–2.5), high evolution2 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 month12–16No criteriaImprovement in DAS28 <1.21
Slovakia60GUIDRheumatology6 monthsModerate to high disease activity1 sDMARD: MTX (15 mg/week) for 3 months12No criteriaModerate disease activity3
Slovenia61REIM=GUIDRheumatologyNo requirementDAS28>4.2 AND SJC>=82 sDMARDs: MTX (20 mg/week) and choice LEFL (20 mg/day) or SSZ (2 g/day)24Improvement in DAS28<1.2No criteria2
Spain62 62aGUIDRheumatologyNo requirementDAS28≥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)12No criteriaDAS28≥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 64GUIDRheumatology+Dermatology+Gastroenterology+Internal medicine+GP+other specialtiesNo requirementDAS28>3.2 and several negative prognostic factors OR
DAS28>5.1
No requirement12No criteriaDAS28>3.2 and several negative prognostic factors3
Switzerland65–67REIMRheumatology+Dermatology+Gastroenterology+Internal medicine+GPNo requirementNo requirement1 sDMARDNANo criteriaNo criteria5
Turkey68REIMRheumatology+other specialtiesNo requirementDAS28>5.13 sDMARDs, including MTX12Improvement in DAS28 <1.2
OR
improvement in DAS28 <0.6 in 3 months
No criteria1
UK69 70REIMRheumatology6 monthsDAS28>5.12 sDMARDs, including MTX26Improvement in DAS28<1.2Improvement in DAS28 <1.21
  • *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.