Supplementary File2
Spanish Society of Rheumatology
Appropriateness Criteria for Reducing the Dose of Biological Therapies in Rheumatoid Arthritis
Variables selected by the Working Group to develop the list of “indications” or “clinical scenarios” in which the appropriateness of the BT dose reduction was evaluated by the Rating Panel
Definitions
1. Rheumatoid arthritis
A patient is considered to have rheumatoid arthritis if 1of the following 2definitions is fulfilled:
a)The 1987 revised criteria for the classification of rheumatoid arthritis (traditional format)1
Criterion / Definition1. Morningstiffness / Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement
2. Arthritis of 3 or more joint
areas / At least 3 joint areas simultaneously have had soft tissue swelling or fluid (not bony overgrowth alone) observed by a physician. The 14 possible areas are right or left PIP, MCP, wrist, elbow, knee, ankle, and MTP joints
3. Arthritis of handjoints / At least 1 area swollen (as defined above) in a wrist, MCP, or PIP joint
4. Symmetricalarthritis / Simultaneous involvement of the same joint areas (as defined in 2) on both sides of the body (bilateral involvement of PIPS, MCPs, or MTPs is acceptable without absolute symmetry)
5. Rheumatoidnodules / Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxta-articular regions, observed by a physician
6. Serumrheumatoid factor / Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in <5% of normal control subjects
7. Radiographicchanges / Radiographic changes typical of rheumatoid arthritis on posteroanterior hand and wrist radiographs, which must include erosions or unequivocallocalizedbony decalcification in, ormost marked adjacent to, the joints involved (osteoarthritis changes alone do not qualify)
PIPS =proximal interphalangeal joints; MCPs = metacarpophalangeal joints; MTPs = metatarsophalangeal joints;
* For classification purposes, a patient shall be said to have rheumatoid arthritis if he/she has satisfied at least 4 of these 7 criteria. Criteria 1to4 must have been present for at least 6 weeks. Patients with 2 clinical diagnoses are not excluded. Rheumatoid arthritis is not to be classedas classic, definite, or probable.
b)The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA2
Target population (who should be tested?): patients whohave at least 1joint with definite clinical synovitis (swelling)*
havesynovitis not better explained by another disease†
Classification criteria for RA (score-based algorithm: add score of categories)
A–D a score of ≥6/10 is needed for classification of a patient as having definite RA‡
Jointinvolvement §
1 largejoint¶ / 0
2−10 largejoints / 1
1−3 small joints (with or without involvement of large joints)** / 2
4−10 small joints (with or without involvement of large joints) / 3
>10 joints (at least 1small joint)†† / 5
Serology (at least 1 test result is needed for classification)‡‡
Negative RF and negative ACPA / 0
Low-positive RF or low-positive ACPA / 2
High-positive RF or high-positive ACPA / 3
Acute-phase reactants (at least 1test result is needed for classification)§§
Normal CRP and normal ESR / 0
Abnormal CRP or normal ESR / 1
Duration of symptoms¶¶
<6 weeks / 0
≥6 weeks / 1
*The criteria are aimed at classification of newly presenting patients. In addition, patients with erosive disease typical of rheumatoid arthritis (RA) anda history compatible with prior fulfillment of the 2010 criteria should be classified as having RA.
Patients with long-standing disease, including those whose disease is inactive (with or without treatment) who, based on retrospectively available data, have previously fulfilled the 2010 criteria should be classified as having RA.
†Differential diagnoses varyin patients with different presentations, but may include conditions such as systemic lupus erythematosus, psoriatic arthritis, and gout. If it is unclear which relevant differential diagnoses to consider, an expert rheumatologist should be consulted.
‡Although patients with a score of less than 6/10 are not classifiable as having RA, their status can be reassessed and the criteria might be fulfilled cumulatively over time.
§ Joint involvement refers to any swollen or tender joint on examination, which may be confirmed by imaging evidence of synovitis. Distal interphalangeal joints, first carpometacarpal joints, and first metatarsophalangeal joints are excluded from assessment. Categories of joint distribution are classified according to the location and number of involved joints, with placement into the highest category possible based on the pattern of joint involvement.
¶Large joints refers to shoulders, elbows, hips, knees, and ankles.
**Small joints refers to the metacarpophalangeal joints, proximal interphalangeal joints, second to fifth metatarsophalangeal joints, thumb interphalangeal joints and wrists.
††In this category, at least 1of the involved joints must be a small joint; the other joints can include any combination of large and additional small joints, as well as other joints not specifically listed elsewhere (eg, temporomandibular, acromioclavicular, sternoclavicular).
‡‡Negative refers to international unit (IU) values that are less than or equal to the upper limit of normal (ULN) for the laboratory and assay; low-positive refers to IU values that are higher than the ULN but ≤3 times the ULN for the laboratory and assay; high-positive refers to IU values that are >3 times the ULN for the laboratory and assay. When rheumatoid factor (RF) information is only available as positive or negative, a positive result should be scored as low-positive for RF.
§§Normal/abnormal is determined according tolocal laboratory standards.
¶¶Duration of symptoms refers to patient self-report of the duration of signs or symptoms of synovitis (eg, pain, swelling, tenderness) of joints that are clinically involved at the time of assessment, regardless of treatment status.
ACPA: anti-citrullinated protein antibody; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate.
2. Current disease activity
Current disease activity is disease activity at the time the decision to reduce the dose of the biological drugarises.Disease activity higher than “low activity” was not taken into consideration because the BT dose is not reducedin these patients3. Therefore, the2categories considered are “remission” and “low activity”, with the following definitions:
a)Remission: Meet 1of the following 4criteria:
Disease Activity Score 28 calculated with ESR (DAS28-ESR): ≤2·6.
Simplified Disease Activity Index (SDAI): ≤3·3.
Clinical Disease Activity Index (CDAI): ≤2·8.
Boolean-based definition of remission from the American College of Rheumatology/European League Against Rheumatism (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. Arthritis Rheum. 2011; 63(3): 573-86.)
b)Low activity. Meet any of the following 3criteria:
Disease Activity Score 28 calculated with ESR (DAS28-ESR):2·6 and ≤3·2.
Simplified Disease Activity Index (SDAI):3·3 and ≤11.
Clinical Disease Activity Index (CDAI): >2·8 and ≤10.
3. Therapeutic goal (TG) in RA
Low activity or remission.4
4. Time on therapeutic goal
Period between when the patient achieves and sustainsthe TGand the decision to taper the BT dose.Time in TG less than 6 months was not taken into consideration because the dose of biological therapy (BT)should not be reduced in these patients before 6 months3. Therefore, 2categories were considered, as follows:
a)More than 12 months.
b)Between 6 and 12 months.
5. Patient age
Age of the patient at the time the decision to reduce dose of biological arises.1Two categories were considered, as follows:
a)70 years old or younger.
b)Older than 70 years.
6. Disease activity at onset
RA activity at the time BT was started.Less than moderate activity was nottaken into considerationbecause it is exceptional to start BTin these patients. Therefore, the2categories considered are moderate and high, with the following definitions:
a)Moderate activity. Meet eitherof the following 2criteria:
Disease Activity Score 28 calculated with ESR (DAS28-ESR): >3·2 and ≤5·1.
Simplified Disease Activity Index (SDAI): >11 and ≤26.
b)High activity: Meet eitherof the following 2criteria:
Disease Activity Score 28 calculated with ESR (DAS28-ESR): >5·1.
Simplified Disease Activity Index (SDAI): >26.
7. Time withAR
Time elapsed from the beginning of the RA symptoms until the time the decision to reduce the BT dose arises, with 2categories:
a)Less than 5 years.
b)Five years or more.
8. Time to achieve the therapeutic goal
Time since the BT started until the TG was reached, with 2categories:
a)Less than 6months.
b)Sixmonths or more.
9. Previous failures with biological therapies (BT)
Suspension of any BT because of lack of effectiveness according to the physician,1 with 3categories:
a)No previous failures with BT.
b)One previous failure with BT.
c)Two or more previous failures with BT.
10. Type of therapy
Type of combination of drug groups used forthe management of RA.1 The 2 categories considered weremonotherapy and combined therapy, with the following definitions:
a)Monotherapy: Treatment with BT without concomitant disease-modifying antirheumatic drugs (DMARDs), regardless of the dose of corticosteroids. The drugs considered to be DMARDs are as follows: methotrexate, leflunomide, sulfasalazine, antimalarials, cyclosporine A, azathioprine, and mycophenolate.
b)Combined therapy: Treatment with BT in combination with some DMARDs, regardless of the dose of corticosteroids. The drugs considered to be DMARDs are as follows: methotrexate, leflunomide, sulfasalazine, antimalarials, cyclosporine A, azathioprine, and mycophenolate.
11. Corticodependence
The patient is on corticosteroids therapy at a dose higher than5 mg/day of prednisone1. The 2 categories considered were without corticodependence and with corticodependence,defined as follows:
a)Without corticodependence:the patient receives corticosteroids at a dose of ≤5 mg/day of prednisone.
b)With corticodependence: the patient receives corticosteroids at a dose of >5 mg/day of prednisone.
12. Active synovitis by ultrasonography
Active synovitis described by an expert in ultrasound diagnostic imaging (this definition was decided by the rating panel).The 3 categories consideredwere as follows:
a)No active synovitis by ultrasound.
b)Active synovitis by ultrasound.
c)Ultrasound exam not performed.
References for Definitions
1.Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31(3): 315-24.
2.Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010; 69(9): 1580-8.
3.Gonzalez-Alvaro I, Martinez-Fernandez C, Dorantes-Calderon B, Garcia-Vicuna R, Hernandez-Cruz B, Herrero-Ambrosio A, et al. Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations for biologics optimization in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Rheumatology (Oxford). 2015; 54(7): 1200-9.
4.Sanmarti R, Garcia-Rodriguez S, Alvaro-Gracia JM, Andreu JL, Balsa A, Caliz R, et al. 2014 update of the Consensus Statement of the Spanish Society of Rheumatology on the use of biological therapies in rheumatoid arthritis. Reumatol Clin. 2015; 11: 279-94.
Figure S1. Proportion of appropriate (green), inappropriate (red), and uncertain (yellow) indications for rheumatoid arthritis
1
FigureS2. Algorithm for easier navigation through the BT dose reduction appropriateness criteria matrix. Click the hyperlink to accessthetable.
Figure S3. Proportion of appropriate (green), inappropriate (red), and uncertain (yellow) indications depending on variables used to develop the list of indications.
1
Table S1.Chapter I.1.a.1.Rheumatoid arthritis.Current disease activity: Remission. Time in TG > 12 months.Age ≤ 70 years.Time to achieve TG < 6 months.
Moderate disease activity at onset / High disease activity at onset / Indications numberDisease duration
< 5 years / Disease duration
≥ 5 years / Disease duration
< 5 years / Disease duration
≥ 5 years
M / Appr. / M / Appr. / M / Appr. / M / Appr.
No previous failures with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 8.5 / A / 8.5 / A / 8.0 / A / 7.0 / A / 1 - 4
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.5 / I / 3.0 / I / 5 - 8
Ultrasound not performed / 7.0 / A / 6.0 / U / 5.5 / U / 5.5 / U / 9 - 12
Withcorticodependence
No active synovitis by ultrasound / 7.5 / A / 6.5 / A / 7.0 / A / 6.0 / U / 13 - 16
Active synovitis by ultrasound / 2.5 / I / 2.5 / I / 1.5 / I / 2.0 / I / 17 - 20
Ultrasound not performed / 5.0 / U / 5.0 / U / 5.0 / U / 5.0 / U / 21 - 24
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 9.0 / A / 8.5 / A / 8.0 / A / 8.0 / A / 25 - 28
Active synovitis by ultrasound / 3.5 / U / 3.5 / U / 3.0 / I / 2.0 / I / 29 - 32
Ultrasound not performed / 7.5 / A / 7.5 / A / 6.5 / A / 6.0 / U / 33 - 36
Withcorticodependence
No active synovitis by ultrasound / 7.5 / A / 7.0 / A / 7.0 / A / 6.0 / U / 37 - 40
Active synovitis by ultrasound / 2.5 / I / 3.0 / I / 2.5 / I / 2.0 / I / 41 - 44
Ultrasound not performed / 6.0 / U / 5.5 / U / 4.0 / U / 5.0 / U / 45 - 48
One previous failure with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 7.0 / A / 6.5 / A / 7.0 / A / 6.0 / U / 49 - 52
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.5 / I / 2.5 / I / 53 - 56
Ultrasound not performed / 6.0 / U / 5.5 / U / 5.0 / U / 5.0 / U / 57 - 60
Withcorticodependence
No active synovitis by ultrasound / 6.0 / U / 5.5 / U / 6.0 / U / 5.5 / U / 61 - 64
Active synovitis by ultrasound / 2.5 / I / 2.5 / I / 2.0 / I / 2.0 / I / 65 - 68
Ultrasound not performed / 5.0 / U / 5.0 / U / 4.5 / U / 4.0 / U / 69 - 72
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 8.0 / A / 7.0 / A / 7.0 / A / 6.0 / U / 73 - 76
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 3.0 / I / 3.0 / I / 77 - 80
Ultrasound not performed / 5.0 / U / 6.0 / U / 5.0 / U / 5.0 / U / 81 - 84
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 6.0 / U / 5.5 / U / 5.0 / U / 85 - 88
Active synovitis by ultrasound / 2.0 / I / 3.0 / I / 2.5 / I / 2.0 / I / 89 - 92
Ultrasound not performed / 5.5 / U / 5.0 / U / 4.0 / U / 5.0 / U / 93 - 96
Two or more previous failures with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 6.0 / U / 6.0 / U / 6.0 / U / 6.0 / U / 97 - 100
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.5 / I / 2.0 / I / 101 - 104
Ultrasound not performed / 5.0 / U / 5.0 / U / 5.0 / U / 5.0 / U / 105 - 108
Withcorticodependence
No active synovitis by ultrasound / 5.5 / U / 5.0 / U / 4.5 / U / 4.5 / U / 109 - 112
Active synovitis by ultrasound / 3.0 / I / 2.5 / I / 2.0 / I / 1.5 / I / 113 - 116
Ultrasound not performed / 4.5 / U / 4.0 / U / 3.5 / U / 3.0 / I / 117 - 120
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.0 / U / 6.5 / A / 6.0 / U / 121 - 124
Active synovitis by ultrasound / 3.0 / I / 3.5 / U / 2.5 / I / 2.5 / I / 125 - 128
Ultrasound not performed / 6.0 / U / 5.5 / U / 5.5 / U / 5.0 / U / 129 - 132
Withcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.0 / U / 5.0 / U / 5.0 / U / 133 - 136
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.5 / I / 2.0 / I / 137 - 140
Ultrasound not performed / 5.0 / U / 4.5 / U / 4.0 / U / 3.0 / I / 141 - 144
TG: Therapeutic goal. BT: Biological therapy. M: Median. Appr.: Appropriateness (A: Appropriate; U: Uncertain; I: Inappropriate).
Table S2. Chapter I.1.a.2.Rheumatoid arthritis.Current disease activity: Remission. Time in TG > 12 months.Age ≤ 70 years.Time to achieve TG ≥ 6 months.
Moderate disease activity at onset / High disease activity at onset / Indications numberDisease duration
< 5 years / Disease duration
≥ 5 years / Disease duration
< 5 years / Disease duration
≥ 5 years
M / Appr. / M / Appr. / M / Appr. / M / Appr.
No previous failures with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 7.0 / A / 7.0 / A / 7.0 / A / 6.5 / A / 145 - 148
Active synovitis by ultrasound / 3.5 / U / 3.5 / U / 3.5 / U / 3.0 / I / 149 - 152
Ultrasound not performed / 5.5 / U / 5.5 / U / 5.0 / U / 5.0 / U / 153 - 156
Withcorticodependence
No active synovitis by ultrasound / 6.5 / A / 5.5 / U / 6.0 / U / 6.0 / U / 157 - 160
Active synovitis by ultrasound / 2.0 / I / 2.0 / I / 2.0 / I / 2.0 / I / 161 - 164
Ultrasound not performed / 5.0 / U / 4.0 / U / 4.5 / U / 4.0 / U / 165 - 168
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 8.0 / A / 8.0 / A / 7.0 / A / 7.0 / A / 169 - 172
Active synovitis by ultrasound / 3.5 / U / 3.5 / U / 3.0 / I / 3.0 / I / 173 - 176
Ultrasound not performed / 6.0 / U / 6.0 / U / 5.0 / U / 5.0 / U / 177 - 180
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 6.5 / A / 6.5 / A / 6.0 / U / 181 - 184
Active synovitis by ultrasound / 2.5 / I / 2.5 / I / 2.5 / I / 2.0 / I / 185 - 188
Ultrasound not performed / 6.0 / U / 5.0 / U / 4.0 / U / 4.5 / U / 189 - 192
One previous failure with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.0 / U / 6.0 / U / 6.0 / U / 193 - 196
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.5 / I / 2.0 / I / 197 - 200
Ultrasound not performed / 6.0 / U / 6.0 / U / 5.0 / U / 5.0 / U / 201 - 204
Withcorticodependence
No active synovitis by ultrasound / 6.0 / U / 6.0 / U / 5.0 / U / 5.0 / U / 205 - 208
Active synovitis by ultrasound / 2.0 / I / 2.5 / I / 2.0 / I / 1.5 / I / 209 - 212
Ultrasound not performed / 5.0 / U / 5.0 / U / 5.0 / U / 4.0 / U / 213 - 216
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 7.5 / A / 6.0 / U / 7.0 / A / 6.0 / U / 217 - 220
Active synovitis by ultrasound / 4.0 / U / 3.5 / U / 3.0 / I / 3.0 / I / 221 - 224
Ultrasound not performed / 6.0 / U / 5.0 / U / 5.0 / U / 5.0 / U / 225 - 228
Withcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.0 / U / 6.0 / U / 5.0 / U / 229 - 232
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.0 / I / 2.0 / I / 233 - 236
Ultrasound not performed / 5.5 / U / 5.0 / U / 4.5 / U / 4.0 / U / 237 - 240
Two or more previous failures with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 5.5 / U / 5.5 / U / 5.0 / U / 5.5 / U / 241 - 244
Active synovitis by ultrasound / 2.5 / I / 3.0 / I / 2.5 / I / 2.5 / I / 245 - 248
Ultrasound not performed / 5.0 / U / 5.0 / U / 5.0 / U / 4.5 / U / 249 - 252
Withcorticodependence
No active synovitis by ultrasound / 5.0 / U / 5.0 / U / 4.5 / U / 5.0 / U / 253 - 256
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.0 / I / 2.0 / I / 257 - 260
Ultrasound not performed / 4.0 / U / 4.0 / U / 4.0 / U / 3.0 / I / 261 - 264
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.5 / A / 5.5 / U / 6.0 / U / 265 - 268
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 3.0 / I / 2.5 / I / 269 - 272
Ultrasound not performed / 5.0 / U / 5.0 / U / 5.0 / U / 4.0 / U / 273 - 276
Withcorticodependence
No active synovitis by ultrasound / 5.5 / U / 5.5 / U / 5.0 / U / 5.0 / U / 277 - 280
Active synovitis by ultrasound / 2.5 / I / 2.0 / I / 1.5 / I / 1.5 / I / 281 - 284
Ultrasound not performed / 5.0 / U / 4.5 / U / 5.0 / U / 3.0 / I / 285 - 288
TG: Therapeutic goal. BT: Biological therapy. M: Median. Appr.: Appropriateness (A: Appropriate; U: Uncertain; I: Inappropriate).
Table S3. Chapter I.1.b.1.Rheumatoid arthritis.Current disease activity: Remission. Time in TG > 12 months.Age > 70 years.Time to achieve TG < 6 months.
Moderate disease activity at onset / High disease activity at onset / Indications numberDisease duration
< 5 years / Disease duration
≥ 5 years / Disease duration
< 5 years / Disease duration
≥ 5 years
M / Appr. / M / Appr. / M / Appr. / M / Appr.
No previous failures with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 9.0 / A / 8.5 / A / 8.0 / A / 8.0 / A / 289 - 292
Active synovitis by ultrasound / 4.0 / U / 4.0 / U / 4.0 / U / 4.0 / U / 293 - 296
Ultrasound not performed / 7.0 / A / 6.5 / A / 7.0 / A / 6.5 / A / 297 - 300
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 7.0 / A / 7.0 / A / 6.5 / A / 301 - 304
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.5 / I / 3.0 / I / 305 - 308
Ultrasound not performed / 5.5 / U / 5.5 / U / 6.0 / U / 5.5 / U / 309 - 312
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 9.0 / A / 8.5 / A / 9.0 / A / 9.0 / A / 313 - 316
Active synovitis by ultrasound / 5.0 / U / 4.0 / U / 3.5 / U / 3.5 / U / 317 - 320
Ultrasound not performed / 7.0 / A / 7.5 / A / 7.5 / A / 8.0 / A / 321 - 324
Withcorticodependence
No active synovitis by ultrasound / 7.5 / A / 7.5 / A / 8.0 / A / 6.5 / A / 325 - 328
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.5 / I / 3.0 / I / 329 - 332
Ultrasound not performed / 6.5 / A / 6.0 / U / 6.5 / A / 6.0 / U / 333 - 336
One previous failure with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 8.0 / A / 7.0 / A / 7.0 / A / 7.0 / A / 337 - 340
Active synovitis by ultrasound / 3.5 / U / 3.5 / U / 3.0 / I / 3.0 / I / 341 - 344
Ultrasound not performed / 6.5 / A / 6.0 / U / 6.0 / U / 6.5 / A / 345 - 348
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 6.5 / A / 6.5 / A / 6.0 / U / 349 - 352
Active synovitis by ultrasound / 2.5 / I / 2.5 / I / 2.5 / I / 2.0 / I / 353 - 356
Ultrasound not performed / 5.5 / U / 5.5 / U / 4.5 / U / 5.5 / U / 357 - 360
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 8.5 / A / 8.0 / A / 7.5 / A / 7.0 / A / 361 - 364
Active synovitis by ultrasound / 4.0 / U / 3.0 / I / 3.0 / I / 3.0 / I / 365 - 368
Ultrasound not performed / 7.5 / A / 7.0 / A / 7.0 / A / 6.0 / U / 369 - 372
Withcorticodependence
No active synovitis by ultrasound / 7.5 / A / 7.0 / A / 7.0 / A / 6.0 / U / 373 - 376
Active synovitis by ultrasound / 3.5 / U / 3.0 / I / 2.5 / I / 3.0 / I / 377 - 380
Ultrasound not performed / 6.5 / A / 6.5 / A / 6.5 / A / 5.5 / U / 381 - 384
Two or more previous failures with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.0 / U / 6.0 / U / 6.0 / U / 385 - 388
Active synovitis by ultrasound / 3.0 / I / 2.5 / I / 2.5 / I / 2.0 / I / 389 - 392
Ultrasound not performed / 6.0 / U / 5.5 / U / 5.0 / U / 5.0 / U / 393 - 396
Withcorticodependence
No active synovitis by ultrasound / 6.0 / U / 6.0 / U / 6.0 / U / 6.0 / U / 397 - 400
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.0 / I / 2.0 / I / 401 - 404
Ultrasound not performed / 5.5 / U / 5.0 / U / 5.0 / U / 5.0 / U / 405 - 408
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 8.0 / A / 7.5 / A / 8.0 / A / 7.0 / A / 409 - 412
Active synovitis by ultrasound / 4.0 / U / 3.5 / U / 3.0 / I / 2.5 / I / 413 - 416
Ultrasound not performed / 7.0 / A / 7.0 / A / 6.5 / A / 6.0 / U / 417 - 420
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 7.0 / A / 6.5 / A / 6.0 / U / 421 - 424
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.5 / I / 2.0 / I / 425 - 428
Ultrasound not performed / 6.0 / U / 5.5 / U / 6.0 / U / 4.0 / U / 429 - 432
TG: Therapeutic goal. BT: Biological therapy. M: Median. Appr.: Appropriateness (A: Appropriate; U: Uncertain; I: Inappropriate).
Table S4. Chapter I.1.b.2.Rheumatoid arthritis.Current disease activity: Remission. Time in TG > 12 months.Age > 70 years.Time to achieve TG ≥ 6 months.
Moderate disease activity at onset / High disease activity at onset / Indications numberDisease duration
< 5 years / Disease duration
≥ 5 years / Disease duration
< 5 years / Disease duration
≥ 5 years
M / Appr. / M / Appr. / M / Appr. / M / Appr.
No previous failures with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 7.5 / A / 7.0 / A / 7.0 / A / 6.0 / U / 433 - 436
Active synovitis by ultrasound / 3.5 / U / 3.5 / U / 2.5 / I / 2.5 / I / 437 - 440
Ultrasound not performed / 7.0 / A / 6.0 / U / 6.0 / U / 5.5 / U / 441 - 444
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 6.0 / U / 6.5 / A / 6.0 / U / 445 - 448
Active synovitis by ultrasound / 2.0 / I / 2.0 / I / 2.0 / I / 2.0 / I / 449 - 452
Ultrasound not performed / 5.0 / U / 5.0 / U / 5.0 / U / 5.0 / U / 453 - 456
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 8.5 / A / 8.0 / A / 8.0 / A / 7.0 / A / 457 - 460
Active synovitis by ultrasound / 4.0 / U / 3.5 / U / 3.0 / I / 3.0 / I / 461 - 464
Ultrasound not performed / 7.0 / A / 7.0 / A / 7.0 / A / 7.0 / A / 465 - 468
Withcorticodependence
No active synovitis by ultrasound / 7.5 / A / 6.5 / A / 7.0 / A / 6.5 / A / 469 - 472
Active synovitis by ultrasound / 2.5 / I / 3.0 / I / 2.5 / I / 2.5 / I / 473 - 476
Ultrasound not performed / 6.5 / A / 6.0 / U / 6.5 / A / 6.0 / U / 477 - 480
One previous failure with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 7.0 / A / 6.0 / U / 7.0 / A / 6.0 / U / 481 - 484
Active synovitis by ultrasound / 3.0 / I / 2.5 / I / 2.5 / I / 2.0 / I / 485 - 488
Ultrasound not performed / 6.0 / U / 6.0 / U / 6.0 / U / 5.5 / U / 489 - 492
Withcorticodependence
No active synovitis by ultrasound / 6.0 / U / 6.0 / U / 6.0 / U / 5.0 / U / 493 - 496
Active synovitis by ultrasound / 2.5 / I / 2.0 / I / 2.0 / I / 1.5 / I / 497 - 500
Ultrasound not performed / 5.0 / U / 5.0 / U / 5.0 / U / 4.5 / U / 501 - 504
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 8.0 / A / 7.5 / A / 7.5 / A / 6.5 / A / 505 - 508
Active synovitis by ultrasound / 4.0 / U / 4.0 / U / 3.0 / I / 2.5 / I / 509 - 512
Ultrasound not performed / 7.0 / A / 6.0 / U / 6.5 / A / 6.0 / U / 513 - 516
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 6.0 / U / 6.0 / U / 6.0 / U / 517 - 520
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.0 / I / 2.0 / I / 521 - 524
Ultrasound not performed / 6.5 / A / 5.5 / U / 6.0 / U / 5.0 / U / 525 - 528
Two or more previous failures with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.0 / U / 6.0 / U / 6.0 / U / 529 - 532
Active synovitis by ultrasound / 3.0 / I / 2.5 / I / 2.0 / I / 2.0 / I / 533 - 536
Ultrasound not performed / 5.5 / U / 5.0 / U / 5.5 / U / 5.0 / U / 537 - 540
Withcorticodependence
No active synovitis by ultrasound / 6.0 / U / 6.0 / U / 6.0 / U / 5.5 / U / 541 - 544
Active synovitis by ultrasound / 2.0 / I / 2.5 / I / 2.0 / I / 2.0 / I / 545 - 548
Ultrasound not performed / 5.0 / U / 4.5 / U / 4.5 / U / 4.0 / U / 549 - 552
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 8.0 / A / 7.5 / A / 7.0 / A / 6.5 / A / 553 - 556
Active synovitis by ultrasound / 3.5 / U / 3.0 / I / 3.0 / I / 2.5 / I / 557 - 560
Ultrasound not performed / 6.5 / A / 6.0 / U / 6.0 / U / 5.0 / U / 561 - 564
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 6.0 / U / 6.0 / U / 6.0 / U / 565 - 568
Active synovitis by ultrasound / 2.5 / I / 2.5 / I / 2.0 / I / 2.0 / I / 569 - 572
Ultrasound not performed / 6.0 / U / 5.0 / U / 6.0 / U / 5.0 / U / 573 - 576
TG: Therapeutic goal. BT: Biological therapy. M: Median. Appr.: Appropriateness (A: Appropriate; U: Uncertain; I: Inappropriate).
Table S5. Chapter I.2.a.1.Rheumatoid arthritis.Current disease activity: Remission. Time in TG 6 - 12 months.Age ≤ 70 years.Time to achieve TG < 6 months.
Moderate disease activity at onset / High disease activity at onset / Indications numberDisease duration
< 5 years / Disease duration
≥ 5 years / Disease duration
< 5 years / Disease duration
≥ 5 years
M / Appr. / M / Appr. / M / Appr. / M / Appr.
No previous failures with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 8.0 / A / 7.0 / A / 8.0 / A / 7.5 / A / 577 - 580
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.0 / I / 2.0 / I / 581 - 584
Ultrasound not performed / 6.5 / A / 6.0 / U / 6.0 / U / 5.0 / U / 585 - 588
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 6.0 / U / 6.5 / A / 6.0 / U / 589 - 592
Active synovitis by ultrasound / 2.0 / I / 2.0 / I / 2.0 / I / 1.5 / I / 593 - 596
Ultrasound not performed / 5.0 / U / 5.0 / U / 5.0 / U / 4.5 / U / 597 - 600
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 8.0 / A / 8.0 / A / 8.0 / A / 7.5 / A / 601 - 604
Active synovitis by ultrasound / 3.5 / U / 3.5 / U / 2.5 / I / 2.5 / I / 605 - 608
Ultrasound not performed / 7.0 / A / 7.0 / A / 7.0 / A / 6.5 / A / 609 - 612
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 7.0 / A / 7.0 / A / 7.0 / A / 613 - 616
Active synovitis by ultrasound / 2.0 / I / 2.5 / I / 2.0 / I / 2.5 / I / 617 - 620
Ultrasound not performed / 5.5 / U / 5.0 / U / 5.0 / U / 5.0 / U / 621 - 624
One previous failure with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 7.0 / A / 7.0 / A / 7.0 / A / 6.5 / A / 625 - 628
Active synovitis by ultrasound / 2.5 / I / 2.0 / I / 2.0 / I / 2.0 / I / 629 - 632
Ultrasound not performed / 6.0 / U / 6.0 / U / 6.0 / U / 5.0 / U / 633 - 636
Withcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.0 / U / 6.0 / U / 5.5 / U / 637 - 640
Active synovitis by ultrasound / 2.0 / I / 2.0 / I / 2.0 / I / 1.5 / I / 641 - 644
Ultrasound not performed / 5.0 / U / 4.5 / U / 5.0 / U / 4.0 / U / 645 - 648
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 8.0 / A / 7.5 / A / 7.0 / A / 7.0 / A / 649 - 652
Active synovitis by ultrasound / 3.5 / U / 4.0 / U / 2.5 / I / 3.0 / I / 653 - 656
Ultrasound not performed / 7.0 / A / 7.0 / A / 6.5 / A / 6.0 / U / 657 - 660
Withcorticodependence
No active synovitis by ultrasound / 7.0 / A / 6.0 / U / 6.0 / U / 5.0 / U / 661 - 664
Active synovitis by ultrasound / 2.5 / I / 3.0 / I / 2.5 / I / 2.5 / I / 665 - 668
Ultrasound not performed / 6.0 / U / 5.0 / U / 6.0 / U / 4.5 / U / 669 - 672
Two or more previous failures with BT
Type of therapy: Monotherapy
Withoutcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.5 / A / 6.0 / U / 6.0 / U / 673 - 676
Active synovitis by ultrasound / 2.0 / I / 2.5 / I / 2.0 / I / 2.0 / I / 677 - 680
Ultrasound not performed / 5.0 / U / 5.0 / U / 5.0 / U / 4.5 / U / 681 - 684
Withcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.0 / U / 6.0 / U / 6.0 / U / 685 - 688
Active synovitis by ultrasound / 2.0 / I / 2.0 / I / 2.0 / I / 2.0 / I / 689 - 692
Ultrasound not performed / 4.5 / U / 3.5 / U / 4.0 / U / 3.0 / I / 693 - 696
Type of therapy: Combined
Withoutcorticodependence
No active synovitis by ultrasound / 8.0 / A / 7.5 / A / 7.5 / A / 7.0 / A / 697 - 700
Active synovitis by ultrasound / 3.0 / I / 3.0 / I / 2.5 / I / 2.5 / I / 701 - 704
Ultrasound not performed / 6.5 / A / 6.0 / U / 6.0 / U / 5.0 / U / 705 - 708
Withcorticodependence
No active synovitis by ultrasound / 6.5 / A / 6.0 / U / 6.5 / A / 6.0 / U / 709 - 712
Active synovitis by ultrasound / 2.0 / I / 2.0 / I / 2.0 / I / 2.0 / I / 713 - 716
Ultrasound not performed / 6.0 / U / 5.0 / U / 5.5 / U / 5.0 / U / 717 - 720
TG: Therapeutic goal. BT: Biological therapy. M: Median. Appr.: Appropriateness (A: Appropriate; U: Uncertain; I: Inappropriate).