Table 3: Comparison of ARAD data with data from selected trials of biological disease modifying therapies for AS.

Study (year) CountryOldroyd et al. van der Heidje et al. (2006) Netherlands [11]Davis Jr. et al. (2003) USA [14] Van der Heidje et al. (2005) Netherlands [15]Breban et al. (2008) France [16]

Design Registry RCT RCT RCT RCT

Inclusion criteriaIn Australia, the PBS criteria for prescription of bDMARDS for AS are: fulfilment of modified NY criteria and failure to respond over 3/12 to at least 2 NSAIDs & an exercise program. (Failure to respond  = BASDAI 4 and ESR 25 mm/hour and/or CRP   10.0 mg/L)(1) 18 years of age(2) Fulfilment modified New York criteria and active AS defined as 2 of: BASDAI score   4 (0–10, 0  = best), morning stiffness   1 hour, VAS for total back pain (0–10, 10  = worst) 4; inadequate response to NSAIDS; and have failed at least one DMARD(1) 18–70 year old(2) Fulfilment modified New York criteria and active AS defined as: score of   30 mm for morning stiffness ( average of 2 scores on a 100 mm VAS); and scores of   30 mm for 2 of the following: patients global assessment (100 mmVAS), back pain, average of 2 VAS scores for night and total back pain and BASFI(1) Fulfilment modified New York criteria for at least 3 months prior to screening with BASDAI score of   4 (0–10, 0  = best) and spinal pain assessment score 4 (VAS 0–10 cm); and normal chest radiograph within 3 months prior to randomization and negative test for latent TB or adequate screening for latent TB(1) 18 years(2) fulfilment Modified New York criteria and 1 of the following: serum CRP more than twice the upper limit of normal; positive findings on MRI of the spine or sacroiliac joints or a vascularised enthesitis on power Doppler ultrasound; BASDAI 3 (0–10, 0  = best) and axial pain (2nd item on BASDAI) 3

Exclusion criteriaNilPrevious receipt of anti-TNF therapy, cyclosporine, azathioprine, or DMARDS (other than sulfasalazine ( 3 gm/day), methotrexate ( 25 mg/wk), hydroxychloroquine ( 400 mg/day), prednisone ( 10 mg/day) and NSAIDS) at any time; receipt intraarticular corticosteroid injections within 4 weeks of baseline; clinically active TB; history of recent infections requiring antibiotic treatment; hepatitis; HIV; significant history of cardiac, renal, neurological, psychiatric, endocrine, metabolic, or hepatic disease; history of demyelinating disease or multiple sclerosis; history of cancer or lymphoproliferative disease (except BCC or SCC or localised cancer of the cervix in situ) Complete ankylosis (fusion) of the spine on radiographic assessment; previous TNF inhibitor therapy; serious infection (associated with hospitalization or intravenous antibiotics) within 4 weeks before screening; pregnancy; any DMARDS within 4 weeks of baseline evaluations (other than hydroxychloroquine, sulfasalazine, methotrexate in stable doses); unstable dosages of NSAIDS or prednisone ( 10 mg/day)Total ankylosis spine (defined by syndesmophytes present on the lateral views of spinal radiographs at all intervertebral levels from T6 through S1); any other inflammatory rheumatic disease; fibromyalgia; a serious infection within 2 months prior to randomization; TB; (active or latent) or recent contact with a person with active TB; an opportunistic infection within 6 months of screening; hepatitis; HIV; a transplanted organ; malignancy; multiple sclerosis; congestive heart failure; taking sulfasalazine or methotrexate within 2 weeks prior to screening; systemic corticosteroids within 1 month prior to screening; anti-TNF therapy other than infliximab within 3 months prior to screening; infliximab at any other time prior to screening; taking DMARDS other than sulfasalazine or methotrexate within 6 months prior to screening or cytotoxic drugs within 12 months of screening Pregnancy or breastfeeding; vaccination with live organism during month prior to study entry; an infection at study entry or had any episode of serious infection within 3 months prior to study entry; active malignancy in 5 years prior to study entry; addicted to drugs or alcohol; severe chronic concomitant disease; receipt of investigational drug in 3 months prior to study entry, or had received any known TNF inhibitor therapy in the past; failure to discontinue DMARDS such as sulfasalazine, MTX, hydroxychloroquine, intramuscular gold, thiol compound, cyclosporine and intravenous biphosphonate   4 weeks prior to enrolment; unstable dose of NSAIDS and corticosteroids for   4 weeks before enrolment.
InterventionNoneAdalimumab 40 mg 1x per 2 weeks for 24 weeksControlEtanercept 25 mg 2x per week for 24 weeksControlInfliximab 5 mg/kg at week 0, 2, 6, 12, 18, over 24 weeksControlInfliximab “continuous” 5 mg/kg every 6 weeks for 54 weeksInfliximab “on demand” 5 mg/kg upon relapse +/− MTX for 54 weeks
Patient numbers35420810713813920178124123
Age, years, mean (SD)45.1 (12.3)*41.7 (11.7)43.4 (11.3)42.1 (24–70) 41.9 (18–65) 40 (32.0–47.0)^41 (34.0–47.0)^41.4 (12.3) 41.3 (10.3)
Males, (%)254 (71.8)157 (75.4)79 (73.8)105 (76.1)105 (75.5)157 (78.1)68 (87.2)93 (60.5)95 (77.2)
Disease duration, years, mean (SD)18.5 (12.1)*11.3 (9.9)10.0 (8.3)10.1 (0–30.7) 10.5 (0–35.3) 7.7 (3.3–14.9)^13.2 (3.7–17.9)^14.6 (10.5) 15.1 (9.3)
HLA-B27 positive (%) /A163 (78)85 (79)108 (84)109 (84)173 (87)69 (89)80 (65)81 (66)
Swollen joint count (0-44 joints) mean (SD) /A1.5 (3.3)1.4 (2.8) /R /R0 (0-1)0 (0-1) /A /A
History of uveitis, (%) /A68 (32.7)27 (25.2)39 (28)43 (31)72 (35.8)25 (32.1)33(27)43 (35)
History of psoriasis, (%) /A68 (32.7)27 (25.2)11 (8)1 5(11)16 (8.0)5 (6.4)20 (16)13 (11)
History of IBD, (%) /A16 (7.7)17 (15.9)7 (5)6(4)13 (6.5)6 (7.7)12 (10)12 (10)
BASDAI (0–10, 0 = best), mean (SD)7.6 (4.5)*6.3 (1.7) 6.3 (1.7) 58.1 (1.5) #59.6 (SEM 1.4) #6.6 (5.3–7.6)^6.5 (5.2–7.1)^6.2 (1.5) 6.2 (1.3)
Patient’s assessment of pain in past week (0-10, 0 = none), mean (SD)44.8 (28.1) (out of 100) 6.4 (2.1)6.7 (2.2) /R /R /R /R6.9 (1.9)6.7 (1.8)
Patient’s global assessment disease activity in the past week (0–10, 0 = none), mean (SD)43.2 (28.0)(out of 100)6.3 (2.2)6.5 (2.0)62.9 (out of 100) 62.9 (out of 100)6.9 (5.7–8.0)^6.7 (5.8–7.7)^7.4 (2.9)7.5 (1.5)
CRP (mg/dl) mean (SD)31.8 (31.9) mg/L*1.8 (2.2) 2.2 (2.9)1.9 (0.2) 2.0 (0.2) 1.5(0.7–3.2)^1.7 (0.7–3.3)^33 (27) mg/L29 (21) mg/L
ESR (mm/hour) mean (SD)35.4 (24.8)* /A /A25.9 (1.8) 25.4 (1.9) /A /A37 (25)32 (21)
SF-36 Physical Component score Mental Health Component score35.4 (10.3) 45.1 (11.2) /R /R /R /A28.8 (23.8–33.7)^47.6 (37.6–54.9)^30.1 (24.9–36.2)^45.0 (33.7–55.5)^33 (7) 34 (10) 31 (7) 36 (10)
AQoL (0-1, 1 = full health) mean (SD)0.55 (0.25) /R /R /A /A /A /A /A /A
S-HAQ (0–3, 0 = no disability), mean (SD)0.86 (0.60) /R /R /A /A /A /A /A /A
Concomitant DMARDS (%)72 (20.3) 40 (19.2)22 (20.6)44 (32)43 (31)0000
  Methotrexate,    (%)50 (14.1)26 (12.5)15 (14.0)15 (11)17 (12)0000
  Sulfasalazine,    (%)22 (6.2)20 (9.6)8 (7.5)29 (21)30 (2)0000
  Leflunomide,    (%)5 (1.4)01 (0.9) /R /R0000
  Prednisolone,    (%)42 (11.9)25 (12.0)6 (5.6)20 (14)18 (13)00 /R /R
Comorbidities
  Gastrointes-tinal disease,    (%)62 (31.3) /A /A /A /A /A /A /A /A
  Hypertension,    (%)51 (25.8) /A /A /A /A /A /A /A /A
  Eye disorders,    (%)32 (14.1) /A /A /A /A /A /A /A /A

* for difference between mean (SD) in ARAD versus weighted mean (SD) in trials means (range) means (SEM) #BASDAI score reported as mean (standard error of the mean) and range 0–100 for this; study ^median (IQR) /A = not measured /R= measured but not reported.