Supplemental Figure 1. Phase 3 studies and timeline of US and European approval of infliximab for auto-inflammatory disorders Phase three studies and timeline of infliximab (IFX) approval by US and European regulatory authorities. In adults IFX therapy is approved for several auto-inflammatory
disorders based on studies in patients with CD76 (1998), rheumatoid arthritis77 (1999), ankylosing spondylitis78 (2003), psoriatic arthritis79 (2004), UC6 (2005) and psoriasis80 (2005). EMA and FDA approved IFX for AS prior to publication of the respective phase 3 studies. FDA approved IFX for psoriatic arthritis prior to publication of the respective phase 3 study. Boxed text represents approval by regulatory authorities based on studies in paediatric IBD from 2007 and 2013.7,25 IFX is not approved in children and adolescents with rheumatoid disease or psoriasis. Black squares represent FDA approval, white circles represent EMA approval for the respective auto inflammatory disorder. Gray circles represent Phase 3 studies from which pharmacokinetic (PK) data was generated. Three studies indicated by (*) generated PK data that was not published in the actual article but where referred to in the Investigators Brochure of IFX.81 IFX, infliximab; EMA, European Medicines Agency; FDA, US Food and Drug Administration. AS, ankylosing spondylitis;
CD, Crohn’s disease; IBD, Inflammatory Bowel Disease; Ps, psoriasis; PsA, psoriatic arthritis; RA, rheumatoid arthritis; UC, ulcerative colitis.
1 2 3 4 5 6 7 8 9 10 11 12
13
Supplemental Table 1 – PHARMACOKINETICS: Infliximab (IFX) concentration and antibodies-to-infliximab (ATIs) in paediatric patients
SUPPLEMENTAL TABLE 1. Infliximab (IFX) concentration and antibodies-to-infliximab (ATIs) in paediatric patients
Study Text N Disease &
Population Age Drug Administration Assay Type used for IFX
& ATI
IFX PK data Immunomodulator
(IM) use ATI prevalence, titer and
time of formation IFX Trough Level and ATI associations Adedokun et
al.25
FT 60 IBD, UC only. Age range 6-17 years
Induction: 5 mg/kg at week 0, 2 and 6, Maintenance: if clinical response, randomized to either 8- or 12-week intervals. During maintenance dose or frequency was increased if no clinical response
IFX &
ATI:ELISA
Concentration:
Induction:
Age: Week 6 TL lower in patients aged 6-11 years vs 12-17 years (7.1 μg/mL vs 15.3 μg/mL) Maintenance:
8-week infusions: 1.9 μg/mL 12- week infusions: 0.8 μg/mL Median biological half-life 10.8 days; range 8.6 -15.4
8-week infusions:
11/22 (50%) 12-week infusions:
13/23 (56.6%)
Prevalence: 7.7%
Titer: ranged from 1:10 to 1:40 in four patients
IFX-TL: Low TL seemed to be associated with lower serum albumin and lower body weight
Burgess et al.41
FT 60 IBD, Crohn only.
Age range 8-17 years, median age 14.1 years (IQR 12.2–15.7 years).
Induction: 5 mg/kg IFX at 0, 2 and 6 weeks.
Maintenance: 5 mg/kg IFX every 8 weeks.
Including inflectra infusions.
IFX &
ATI:ELISA
Concentration:
Induction: median IFX-TL postinduction was 8.4 μg/mL (week 6 median=10.9 μg/mL;
weeks 11–14 median 5.9 μg/mL) Maintenance: significantly lower than median IFX-TL of patients postinduction (4.0 μg/mL;
p<0.001).
56/60 (93%), 60/60 at start of IFX
Prevalence: 8%
Titer: 135, 57, 35, 15 and 7.6 U/mL
NR
Candon et al.30
FT 28 IBD, Crohn only.
Age range 6 months - 15 years mean age 10.5 ± 3.3 years
Induction: 5 mg/kg, either 1 infusion or a series of 3 infusions at week 0, 2 and 6.
Maintenance: in case of relapse 5 or 10 mg/kg on demand, or 8-week interval
IFX &
ATI:ELISA
Concentration:
Induction: Week 2: 16.7 ± 7.3 μg/mL. Week 6: 8.8 ± 7.1 μg/mL
27/28 (96.6%) Prevalence: 35.7%
Titer: ranged from 1:8000 to 1:100
Time of Formation:
- One infusion as induction: ATIs detected after 1st infusion in two patients, after 2nd infusion in two other patients. Three patients showed ATIs following 6th, 7th and 12th infusion.
-Series of 3 induction infusions:
ATIs detected between 3rd and 9th infusion
ATIs: difference in ATIs between clinical response vs loss of response (3/14 (21.4%) vs 6/8 (75%); p= 0.026)
Cardile et al.19 A 15 IBD. Not specified NR IFX:ELISA, ATI:
NR
Concentration:
Maintenance: 5.5 μg/mL (range 0.1-14.9). No difference between CD and UC (2.5 vs 3.2 μg/mL;
p=0.6).
NR Prevalence: 13.3%
Titer: 2 ATI positive patients (2.4 and 1.5 OD) also had low level of serum IFX
IFX-TL: low serum IFX (median 0.03 μg/mL) was associated with high CRP during maintenance
14
SUPPLEMENTAL TABLE 1. (Continued)
Chi et al.29 FT 223 IBD. Mean age 18.5 years (SD 4.4), percentage
<18 years of age not specified
Cross-sectional: mean IFX dose of 10.39 mg/kg (SD 4.72) per 8 weeks
IFX &
ATI:HMSA
Concentration: Overall, mean IFX- TL of all patients was 13.6 μg/mL (SD ± 11.1.)
84/223 (37.7%), mostly MTX (71 of 84).
Within the current monotherapy group, 112/139 (80.6%) had previously been on combination therapy (105/112 before IFX start; 2/112 within 3 months after IFX start;
3/112 3 months after start of IFX), while 27 (19.4%) had never been on a concomitant IM.
Prevalence: 16.1% IFX-TL: Patients with CRP >0.5 mg/dL had a lower IFX-TL compared with those with CRP
≤0.5 mg/dL (12.03 vs 15.96 μg/mL, P = 0.03).
No association was found between IFX-TL and BMI, ESR or albumin. Patient age was positively associated with IFXL (β estimate = 0.31, P = 0.04).
Choi et al.34 FT 39 IBD. Median age (IQR) reported per group. Group A (remission); 14.7 yrs (13.3–17.5), Group B (poor response); 14.8 yrs (9.0–18.8)
NR IFX &
ATI:ELISA
Concentration:
Maintenance: IFX-TLs in patients in clinical remission group (n=16;
median, 3.99 μg/mL; IQR, 0.30 to 21.96). IFX-TL in patients with poor response group (n=23;
median, 0.88 μg/mL; IQR, 0.00 to 6.80)(p=0.002).
100% Prevalence 17.9% IFX-TL: ESR, CRP, Albumin not significantly
associated with IFX-TL statistically.
ATIs: In 7/39 (17.9%) patients, all in group of poor response (30.4% of this group)
Deora et al.35 FT 73 IBD. Median age 16.12 years (IQR 14.34-17.91 years)
NR IFX:ELISA, ATI:
NR
Concentration: TDM was performed due to concerns about clinical disease activity in 24/107 (22.4%) of measurements, 83/107 were routine test. Of these measurements, 38/107 (35.5%) IFX-TLs were suboptimal (<3.5 μg/mL), with a median level of 1.8 μg/mL (range 0.04–3.4 μg/mL).
52/73 (71%) NR NR
Dubinsky et al.36
FT 50 Pediatric, mean
age 12.46 years (SD 3.11). Age range 7-20 years.
Induction: 5 mg/kg at weeks 0, 2, and 6 Maintenance: first dose at week 14.
IFX &
ATI:ELISA
NR 22% Prevalence: A total of 14 of 50
(28%) patients had detectable ATI Time of Formation: In 7 patients ATIs were detected at week 14 (14%), and in 7 patients at week 54 or at early termination.
NR
El-Matary et al.47
FT 27 IBD, Crohn only.
Mean age 12.5 ± 5.1 years
Induction:
median [IQR], 6 [5.8–7.8]
mg/kg at weeks 0, 2 and 6.
Maintenance: Dose 4 followed the third dose at a median time interval (IQR) of 50 (42–57) days.
IFX:ELISA, ATI:
NR
Concentration:
Induction: median pre–fourth dose IFX-TL in the group with healed fistulae or fistulae in the process of healing was 12.7 μg/mL (IQR; 6.6–15.5) compared with 5.4 μg/mL (2.7–8.4) in the nonresponsive perianal CD disease group (P = 0.02).
23/27 (85%) NR NR
Hadigan et al.26
A 21 IBD, Crohn only.
Age range 8-17 years (mean age 15.1 years)
Single infusions with either 1, 5 or 10 mg/kg
IFX & ATI:NR Concentration: Serum IFX concentration after one IFX infusion proportional to dose; 4.0 μg/mL, 40.2 μg/mL, 88.6 μg/mL at week 1 following the infusion for 1, 5, and 10 mg/kg Clearance: Biological half-life for IFX was 4.8, 9.3, and 9.5 days for 1, 5, and 10 mg/kg
NR Prevalence: 0%
NR
Hämäläinen et al. 43
FT 37 IBD. Median age
14 years. Age range 5.6 - 18 years
Induction: 5 mg/kg at week
0, 2, and 6
Maintenance: 5 or 10 mg/kg at an 8-week interval
IFX &
ATI:ELISA
Concentration:
Induction: 17.6 μg/mL (0–48), Age: Young children with lower body weight had significantly lower concentrations at week 2 (p<0.001) and week 6 (p=0.0445).
Concentrations shown in article (figure 1)
Maintenance: 3.55 μg/mL (2.7–
12.1)
31/37 (84%) Prevalence: 18%
Time of Formation: Three patients with ATI at week 6, weeks not mentioned for other patients
IFX-TL: IFX-TL at week 2 was associated with total milligrams of IFX, indicative of patient body weight. High serum IFX concentration was associated with low fecal calprotectin levels during induction
ATI: No clear association between ATIs and loss of response. In three particular patients the presence of ATI seemed to associate with poor outcome of IFX therapy
Hoekman et al.44
FT 39 IBD. Median age
15 years. Age range 12.9 - 16.3 years
All patients had an 8- week interval, 7/39 were receiving >5mg/kg
IFX &
ATI:ELISA
Concentration:
Maintenance: In cross-sectional analysis median IFX-TL was 3.5 μg/mL, 38% lower and 23%
higher than therapeutic range of 3-7 μg/mL
46% (18/39) Prevalence: 10.3%
Titer: Four patients had ATIs detected at least at one time point (14, 22, 28, and 485 AU, respectively)
IFX-TL: In patients with 5 mg/kg IFX dose, negative correlation of IFX-TL with fecal calprotectin (p<0.01) and CRP (p<0.01).
Positive correlation between IFX-TL and albumin (p< 0.01)
ATI: No clear association between ATIs and loss of response. Two patients were in clinical remission despite ATI
Hofmekler et al. 37
FT 129 IBD. Age at diagnosis given per disease phenotype
Induction: 5 mg/kg at 0, 2, 6 weeks
Maintenance: 5 mg/kg every
6 or 8 weeks.
IFX &
ATI:HMSA, ECL
Concentration:
Maintenance: Serum IFX was detected in 212 samples (88.0%) with a median level of 11.8 μg/mL (IQR 5.9–17.7). Patients receiving a dose of 5 mg/kg at Q6 week interval exhibited significantly higher IFX level than Q8 week interval (9.8 μg/mL (4.6–
15.9) vs 5.6 μg/mL (2.9–
11.4);P=0.009.
6/129 (4.7%) Prevalence 22.5%
Time of Formation: No actual data. Estimated annual risk of development of ATI at 13 per 100 personyears, authors suggest that LOR is likely because of antibody development
IFX-TL: Median IFX level was statistically higher for patients with age above 17 years (P=0.010).
ATIs: median IFX level for patients without ATI was 11.8 μg/mL vs 0 μg/mL for patients with ATI (P<0.001).
Hyams et al.7 FT 112 IBD, Crohn only.
Mean age 13.3 years (SD 2.5)
Induction: 5 mg/kg at week 0, 2 and 6, Maintenance: if clinical response at week 10 randomized to either 8- or 12-week intervals
IFX & ATI:NR Clearance: median biological half- life 10.7 days; range 7.4 -15.2
112/112 (100%) Prevalence: 2.9%
Time of Formation: one at week 16, one at week 22, one at week 54
NR
SUPPLEMENTAL TABLE 1. (Continued)
Kansen et al.38 FT 229 IBD, Crohn only.
Median age at start of IFX 14.4 years (IQR: 12.6–
15.9)
Induction: infusions at 0, 2, and 6 weeks Maintenance: 5 mg/kg every 8 weeks.
IFX:ELISA, ATI:
ECL, ELISA
NR A total of 201 patients
(88%); continuous combined
immunosuppression (CCI) group 86 patients (38%), early combined suppression (ECI group) 115 patients (50%)
Prevalence: 15%
Titer: median level of ATIs at first positive titer measurement was 63 AU/mL (IQR 25–430).
Time of Formation: Kaplan-Meier estimates on probability of remaining ATI free at 12, 24, and 36 months after introduction of IFX in CCI group were 93.4%, 91%, and 91%, respectively. In ECI group 97.5%, 93%, and 85.6%
respectively and in the IFX monotherapy group 72.6%, 57.7%, and 48.1% respectively.
Confidence intervals in article.
ATIs: Sixteen out of 25 patients (64%) with ATIs had LOR, compared with 32 of 137 patients (19%) without ATIs (P<0.00002, log rank 0.02).
Mehrotra et al.27
A 60 IBD, UC only. Aged
6 through 17 years
Induction: 5 mg/kg at weeks 0, 2, and 6.
Maintenance:
Responders at week 8 were randomized to 5 mg/kg every 8 or 12 weeks with an option to increase dose or dosing frequency in case of loss of response
IFX & ATI:NR Concentration:
Induction: Adult UC clinical trial data (not specified) was used for comparison. Week 8 median IFX serum concentrations were similar between children and adults (29 lg/ml vs 33 lg/ml).
Steady-state TLs in paediatric patients were slightly lower compared to adults (1.9 lg/ml vs 2.5 lg/ml).
NR. Assumed 100%
given inclusion criteria
NR NR
Merras- Salmio et al.39
FT 146 IBD. Median age 14.8 years
Induction: IFX 5 mg/kg at weeks 0, 2, 6.
Maintenance: dosage at discretion of clinician, at 5- to 10-week intervals.
IFX &
ATI:ELISA
Concentration:
Induction: Median IFX-TL after induction therapy was 8.0 mg/L.
Maintenance: median IFX-TL was lower at 2.8 mg/L. Significantly lower IFX-TLs in CD compared to UC patients (respective medians 2.6 and 4.4 mg/L, P<0.0.001).
58/165 infusion regimens (including reinductions) (35%).
Both AZA n=54 (33%) and MTX n=2 (2%)
Prevalence: 25%
Titer: NR
Time of Formation: median time of ATI detection at 5th infusion (further information not in table)
IFX-TL: No significant difference between patients weighing<35 compared to >35 kg (median IFX-TL 2.0 mg/L (IQR 0.9–4.5, n=34) vs 3.4 mg/L (IQR 1.5–5.5, n=241); P=0.081). In both groups, median IFX dose was 5 mg/kg/8 weeks (IQR 4.7–5.8). Age correlated with weight-standardized IFX dose (r2=0.1238, P<0.001), indicating younger patients received higher IFX doses.
ATIs: Lower in patients in remission compared to patients with adverse effects causing IFX discontinuation (4% vs 54%; P<0.001) Miele et al.31 FT 34 IBD. Median age
14.8 years. Age range 6.4-22.5 years
IFX 5 mg/kg administered periodically, in case of loss of efficacy 10 mg/kg was given
IFX &
ATI:ELISA
NR 29/34 (85.3%) Prevalence: 35.3%
Titer: Levels of ≥ 8.0 μg/mL more common in patients with average interval of 8 weeks or less (p=
0.04) between infusions. Interval duration > 12 weeks had no effect on ATI prevalence (p=0.89)
ATIs: ATI positivity associated with higher rate of infusion reactions (p<0.01). These occurred in a higher proportion of infusions given to patients with ATI positivity than patients without ATI (13.8% vs 3.6%)
Minar et al.32 FT 72 IBD, Crohn only.
Mean age 13 years (SD 4)
Thirty (42%) patients had intensified (≥7.5 mg/kg or ≤ 6-week intervals) IFX dosing regimen before initial IFX testing
IFX &
ATI:ELISA, HMSA
Concentration:
Maintenance: Concentrations reported only in subselection of 55 patients (See Table 1). IFX concentrations were also determined mid-interval, inbetween infusions
18/72 (25%) Prevalence: 19%
Time of formation: ATIs in 14 patients, 5 occurring in the first year of therapy (median of 483 days and min-max range of 149–
1699 days to detection)
IFX-TL: Undetectable TL or ATI associated with elevated ESR
Minar et al.45 A 37 IBD, Crohn only.
Mean age 15 years.
NR IFX:ELISA NR 4/37 (10.8%) NR IFX-TL: Lower in IFX failure patients compared
to those remaining in remission (mean 1.6 μg/mL (SD 1.3) vs mean 3.5 μg/mL (SD 3.5)).
However, not statistically significant (p= 0.1) Ohem et al.48 FT 65 IBD, Crohn only.
Median age at first IFX 14 years (IQR 11.4–16.4)
Induction: no data.
Current IFX maintenance treatment, including intensified therapy, at the time of enrolment (shortened interval, increased dose). Infusion interval was 4 [q4] to 8 [q8] weeks.
IFX &
ATI:ELISA
Concentration:
Maintenance: In a model that used Calprotectin ≤100 μg/g as the definition
of remission, the optimal IFX-TL was 3.5 μg/mL.
51/65 participants (78%), 408/539 samples tested (76%)
Prevalence: 4.1% IFX-TL: Higher CRP level, ESR, and fecal calprotectin levels associated with lower IFX levels. Lower levels of IFX were associated with ATIs positivity (OR 0.027, 95% CI 0.009–
0.077). Authors found an independent association between IFX levels and serum albumin levels (OR 1.364, 95% CI 1.169–1.593;
p < 0.001).
ATIs: No independent association between remission and ATIs.
Rivera et al.20 A 69 IBD. Mean age 16.3 ± 3.0 years, 67% <18 years and 33% 18-22 years old
The median dose of IFX was 6.0 mg/kg (range 3.8 - 11.4 mg/kg)
IFX:ECL, ATI:
ECL
Concentration:
Induction: 28.0 μg/mL Maintenance (4.3 μg/mL, significantly lower compared to induction (p<0.001).
IFX concentration significantly lower in patients with detectable vs undetectable ATIs (1.8 vs 9.0 μg/mL; p<0.001)
36/69 (52.2%), 25%
with thiopurines and 75% with MTX
Prevalence: 41%
Titer: median ATI concentration 113 ng/ml (range: 24-1304)
IFX-TL: inverse relationship with ATIs (p<0.001)
Rolandsdotter et al.40
FT 45 IBD. Median age
at inclusion 16 years (range 7–18 years)
Induction: no data, inclusion criteria was current maintenance treatment.
Maintenance: Median dose 6.2 mg/kg (range 3.44–10.5)
IFX &
ATI:ELISA
Concentration:
Maintenance: Mean IFX-TL was 5.2 μg/mL, median IFX-TL 4.5 μg/mL (range from <0.2 to 21)
29/45 (64%) at any time during study
Prevalence 18.0% IFX-TL: IFX-TL correlated with ESR, CRP, and albumin.
ATIs: None of the 8 children with ATI were in remission at time of ATI positive samples.
Rosenthal et al.21
A 38 IBD. Median age
12.6 years
NR IFX &
ATI:ELISA
NR NR Prevalence: 8% at week 14 and
20% at week 54 or early termination
Time of formation: Two patients during induction. ATI detected in 8% at week 14 and 20% at week 54 or at early termination.
IFX-TL: IFX-TL at week 14 was associated with week 54 IFX-TL (p = 0.02) and inversely associated with ATIs at week 54 (p = 0.003)
SUPPLEMENTAL TABLE 1. (Continued)
Schatz et al.22 A 50 IBD. Not specified NR IFX & ATI:NR NR NR Prevalence: 38%
Time of formation: earliest occurrence of ATI before the 2nd infusion
ATIs: Associated with acute allergic reactions (4/4) and loss of response (10/16). If ATI occurred they persisted, except in four patients with low titers which turned negative after IFX dose escalation or reintroduction of azathioprine.
Singh et al.46 FT 58 IBD. Median age reported at diagnosis 11.4 years (range, 6.6–
18.4)
Induction: 5 mg/kg at week 0, 2 and 6, Maintenance: IFX escalation was not specified
IFX &
ATI:ELISA, HMSA
Concentration:
Induction: Median [IQR] IFX-TL at week 14 was 5.1 [3.1–7.5] μg/mL Maintenance: Median [IQR] IFX- TL at week 54 was 5.2 [3.7–9.1]
μg/mL
25/58 (43%) Prevalence: 10% at week 14 and 26% at week 54
IFX-TL: Lower IFX-TL at week 14 correlated with higher CRP levels at week 14 (p<0.0001). Week 14 and 54 median IFX-TLs were numerically but not statistically higher in patients on combo therapy vs monotherapy (Week 14: 6.8 vs 3.1 mg/mL; p =0.14 and week 54: 7.6 vs 3.45 mg/mL; p = 0.29, respectively).
Stein et al.49 FT 77 IBD, Crohn only.
Median age at start of IFX 14.79 years (IQR, 12.20–
16.81 years)
Induction dosing was given at 0, 2, and 6 weeks at a dose of 5 mg/kg followed by standard maintenance dosing.
IFX &
ATI:HMSA
Concentration:
Induction: Median (IQR) IFX-TL at week 10: 16.80 μg/mL (9.00–
35.00)
Maintenance: 6 months 3.80 μg/mL* (0.90–7.90), and 12 months: 5.85 μg/mL** (1.05–
11.05) after start of IFX.
(* excludes 8 patients off of IFX,
** excludes 17 patients off of IFX at time of respective
measurement)
At baseline total of 42/77 (55%), 28/77 (36%) on AZA/6-MP, 14/77 on MTX (18%)
Prevalence 23.0% ATIs: Undetectable ATI at 10 weeks was associated with ongoing IFX therapy at 12 months (P = 0.008).
Turon et al.23 A 64 IBD. Mean age 16
± 2.8 years
NR IFX & ATI:NR Concentration: 11.7 ± 10.3
μg/mL; range 1.4-40
NR Prevalence: 16% of all assays,
number of patients not reported
Titer: 9.85 ± 3.70 μg/ ml; range 2.24-15.97
ATIs: No clear association between ATIs and loss of response. Formation of ATI in paediatric IBD patients could be successfully managed as 74% of patients with ATIs continued IFX and clinically improved or maintained remission at one year
Vahabnezhad et al. 33
FT 188 IBD. Age <21 yr, median (IQR) age at IFX induction 13 years (10-15)
In case of sustained durable remission 5 mg/kg every 7-8 weeks, dose intensification to 10 mg/kg and/or shortening of interval to every 6 weeks or less
IFX & ATI:NR NR CD: 65% vs UC:35%
either thiopurines or MTX during IFX induction.
Prevalence: In patients failing IFX 25% of CD patients and 11% of UC patients
Time of Formation: Six patients had infusion reactions within the induction period. Half (3/6 patients) had ATIs.
ATIs: After dose intensification, significant more patients that did not recapture response had detectable ATI compared to patients that did recapture response (73% vs 22%; p=0.002)
Van Hoeve et al.42
FT 52 IBD. Median age
13.0 years [11.1–
15.0]
Induction: IFX 5 mg/kg at weeks 0, 2, 6. IFX induction regimens subject to intensification based on disease severity at the discretion of the treating physician.
Maintenance: 5 [4.0–6.0]
weeks median dosing interval; 32.2% received dose intensification up to 15 mg/kg. Overall median standardized IFX dose 8 [6.7–13.3]
mg/kg/8 weeks.
IFX & ATI:
ELISA
Concentration:
Maintenance: median IFX-TL was 5.0 [3.2–7.3] μg/mL
40/52 at start of maintenance (75%)
Prevalence: 0.15% (1/686 measurements)
Titer: 51 ng/mL (n=1)
IFX-TL: Significant correlation with weight [rs = 0.291, p = 0.036], height [rs = 0.280, p = 0.047], and body surface area [BSA] [rs = 0.305, p = 0.030]. In subgroup of patients with weight <
34 kg, IFX-TLs were significantly lower in comparison with higher weight class [p = 0.043]. Younger patients did not have significantly lower IFX-TLs [rs = 0.244, p = 0.082]. Significant correlation of IFX-TLs with CRP [rs = -0.505, p = 0.001] and ESR [rs = -0.460, p = 0.001], but not albumin [rs = 0.260, p = 0.066]. In addition, significant correlation between IFX-TLs and haemoglobin [rs = 0.323, p = 0.020], but not platelets [rs = -0.226, p = 0.107].
Wilson et al.24 A 55 IBD. Not specified NR IFX &
ATI:HMSA, ECL
NR NR Prevalence: 47% NR
Zitomersky et al.28
FT 134 IBD. Mean age 17.3 years ± 4.3 years
NR IFX &
ATI:HMSA
Concentration: Patients with >5 mg/kg vs standard dose (median IFX-TL 14.5 μg/mL; IQR, 8.7–29 vs 7.9 μg/mL; IQR, 3.6–12.7; p=
0.004)
50/134 (37.3%) Prevalence: 20%
Titer: Reported in Table 1 as thresholds (≥5, ≥10, ≥ 12 or ≥15 U/ml)
IFX-TL: Lower IFX-TL in patients with ATI ≥5 U/mL compared to ATI <5 U/mL (1.0 μg/mL vs 12.2 μg/mL; p< 0.001). Previous IM use was almost significantly associated with IFX-TL (p=0.06); 79% with IFX-TL < 3μg/mL vs 94%
with IFX-TL ≥3 μg/mL had taken IM previously.
ATIs: Correlated with progression to surgery.
ATI <5 U/mL associated with longer duration of IFX therapy compared with those with ATI≥5 U/mL (27.6 vs 19.2 months; p= 0.01) A, Abstract; ATI, antibodies-to-infliximab; CD, Crohn’s disease; CRP, C-reactive protein; ECL, Electrochemiluminescence; ELISA, enzyme-linked immunosorbent assay; ESR, Erythrocyte sedimentation rate; FT, full text; HMSA,homogenous mobility shift assay; IBD, Inflammatory Bowel disease; IFX-TL, infliximab trough level; IQR, interquartile range; NR, not reported; PK, pharmacokinetic; SD. Standard deviation; UC, ulcerative colitis