Ankylosing Spondylitis Patients Commencing Biologic Therapy Have High Baseline Levels of Comorbidity: A Report from the Australian Rheumatology Association Database
Table 3
Comparison of ARAD data with data from selected trials of biological disease modifying therapies for AS.
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
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)
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 (%)
/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)
/A
1.5 (3.3)
1.4 (2.8)
/R
/R
0 (0-1)
0 (0-1)
/A
/A
History of uveitis, (%)
/A
68 (32.7)
27 (25.2)
39 (28)
43 (31)
72 (35.8)
25 (32.1)
33(27)
43 (35)
History of psoriasis, (%)
/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, (%)
/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)#
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
/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)
2.0 (0.2)
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)*
/A
/A
25.9 (1.8)
25.4 (1.9)
/A
/A
37 (25)
32 (21)
SF-36 Physical Component score Mental Health Component score
35.4 (10.3) 45.1 (11.2)
/R
/R
/R
/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)
/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)
0
0
0
0
Methotrexate, (%)
50 (14.1)
26 (12.5)
15 (14.0)
15 (11)
17 (12)
0
0
0
0
Sulfasalazine, (%)
22 (6.2)
20 (9.6)
8 (7.5)
29 (21)
30 (2)
0
0
0
0
Leflunomide, (%)
5 (1.4)
0
1 (0.9)
/R
/R
0
0
0
0
Prednisolone, (%)
42 (11.9)
25 (12.0)
6 (5.6)
20 (14)
18 (13)
0
0
/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.
