Table 3.
Comparison of ARAD data with data from selected trials of biological disease modifying therapies for AS.
| Study (year) Country | Oldroyd 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 | ||||
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| Inclusion criteria | In 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 | ||||
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| Exclusion criteria | Nil | Previous 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. | ||||
| Intervention | None | Adalimumab 40 mg 1x per 2 weeks for 24 weeks | Control | Etanercept 25 mg 2x per week for 24 weeks | Control | Infliximab 5 mg/kg at week 0, 2, 6, 12, 18, over 24 weeks | Control | Infliximab “continuous” 5 mg/kg every 6 weeks for 54 weeks | Infliximab “on demand” 5 mg/kg upon relapse +/− MTX for 54 weeks |
| Patient numbers | 354 | 208 | 107 | 138 | 139 | 201 | 78 | 124 | 123 |
| Age, years, mean (SD) | 45.1 (12.3)* | 41.7 (11.7) | 43.4 (11.3) | 42.1 (24–70)α | 41.9 (18–65)α | 40 (32.0–47.0)^ | 41 (34.0–47.0)^ | 41.4 (12.3) | 41.3 (10.3) |
| Males, N (%) | 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)α | 10.5 (0–35.3)α | 7.7 (3.3–14.9)^ | 13.2 (3.7–17.9)^ | 14.6 (10.5) | 15.1 (9.3) |
| HLA-B27 positive N (%) | N/A | 163 (78) | 85 (79) | 108 (84) | 109 (84) | 173 (87) | 69 (89) | 80 (65) | 81 (66) |
| Swollen joint count (0-44 joints) mean (SD) | N/A | 1.5 (3.3) | 1.4 (2.8) | N/R | N/R | 0 (0-1) | 0 (0-1) | N/A | N/A |
| History of uveitis, N (%) | N/A | 68 (32.7) | 27 (25.2) | 39 (28) | 43 (31) | 72 (35.8) | 25 (32.1) | 33(27) | 43 (35) |
| History of psoriasis, N (%) | N/A | 68 (32.7) | 27 (25.2) | 11 (8) | 1 5(11) | 16 (8.0) | 5 (6.4) | 20 (16) | 13 (11) |
| History of IBD, N (%) | N/A | 16 (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)β # | 59.6 (SEM 1.4)β # | 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) | N/R | N/R | N/R | N/R | 6.9 (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)β | 2.0 (0.2)β | 1.5(0.7–3.2)^ | 1.7 (0.7–3.3)^ | 33 (27) mg/L | 29 (21) mg/L |
| ESR (mm/hour) mean (SD) | 35.4 (24.8)* | N/A | N/A | 25.9 (1.8)β | 25.4 (1.9)β | N/A | N/A | 37 (25) | 32 (21) |
| SF-36 Physical Component score Mental Health Component score | 35.4 (10.3) 45.1 (11.2) | N/R | N/R | N/R | N/A | 28.8 (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) | N/R | N/R | N/A | N/A | N/A | N/A | N/A | N/A |
| S-HAQ (0–3, 0 = no disability), mean (SD) | 0.86 (0.60) | N/R | N/R | N/A | N/A | N/A | N/A | N/A | N/A |
| Concomitant DMARDS n (%) | 72 (20.3) | 40 (19.2) | 22 (20.6) | 44 (32) | 43 (31) | 0 | 0 | 0 | 0 |
| Methotrexate, N (%) | 50 (14.1) | 26 (12.5) | 15 (14.0) | 15 (11) | 17 (12) | 0 | 0 | 0 | 0 |
| Sulfasalazine, N (%) | 22 (6.2) | 20 (9.6) | 8 (7.5) | 29 (21) | 30 (2) | 0 | 0 | 0 | 0 |
| Leflunomide, N (%) | 5 (1.4) | 0 | 1 (0.9) | N/R | N/R | 0 | 0 | 0 | 0 |
| Prednisolone, N (%) | 42 (11.9) | 25 (12.0) | 6 (5.6) | 20 (14) | 18 (13) | 0 | 0 | N/R | N/R |
| Comorbidities | |||||||||
| Gastrointes-tinal disease, N (%) | 62 (31.3) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Hypertension, N (%) | 51 (25.8) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Eye disorders, N (%) | 32 (14.1) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
*P < .001 for difference between mean (SD) in ARAD versus weighted mean (SD) in trials
α means (range)
β means (SEM)
#BASDAI score reported as mean (standard error of the mean) and range 0–100 for this; study ^median (IQR)
N/A = not measured
N/R= measured but not reported.