Mean Adalimumab Research Articles

Effects of Adalimumab Entering National Reimbursement on Medical Costs for Patients With Psoriasis: A 4-Year Single-Center Retrospective Study in China

Objective: Adalimumab (ADA) is expensive and rarely used among patients. However, its cost for moderate to severe chronic plaque psoriasis can now be reimbursed since its addition to the National Reimbursement Drug List (NRDL) in January 2020. Therefore, we conducted this study to estimate the medical cost of ADA and its influencing factors in patients with psoriasis using ADA and thus gain a better understanding of the effect of the NRDL adjustment in China. Methods: This retrospective study evaluated the medical cost of ADA before and after the addition of ADA to the NRDL (2018—2022) among 320 patients in a large professional dermatology specialty hospital. Descriptive analysis, Welch’s analysis of variance, and multiple regression analysis were used to evaluate the medical cost and influencing factors. Results: Before ADA was added to the NRDL, patients’ mean total cost and ADA cost were ¥24,243.56 ± 16,346.53 and ¥20,391.11 ± 14,440.69, respectively. After ADA became covered by the NRDL, the above 2 expenses decreased to ¥10,461.19 ± 7,554.66 and ¥8,775.27 ± 7,092.16, respectively. This significant decrease in the cost of ADA resulted in a significant 110.5-times increase in ADA use. Statistically significant differences were found in the total cost, patient type (outpatient/inpatient), insurance status (yes/no), reimbursement status (before/after), and age. Medical insurance reimbursement (P < 0.001, β = -0.468, before reimbursement = 1, after reimbursement = 2) was the most significant influencing factor, followed by patient type (P = 0.018, β = -0.215, outpatient = 1, inpatient = 2) and age (P = 0.0046, β = -0.174). Conclusion: Medical insurance reimbursement is the most important factor affecting patients’ total cost of ADA by reducing the economic burden, enhancing the availability of ADA, and stimulating the need for treatment.

Adalimumab Serum Concentrations, Clinical and Endoscopic Disease Activity in Crohn’s Disease: A Cross-Sectional Multicentric Latin American Study

Despite some variability in ideal serum Adalimumab (ADA) concentrations, there is increasing evidence that higher concentrations of anti-TNF-α agents can be associated with sustained efficacy, and low or undetectable levels may lead to loss of response. This study aims to correlate serum ADA concentrations with clinical and endoscopic activity in patients with Crohn's disease (CD). A cross-sectional and multicentric study was performed with patients with CD, who used ADA for at least 24 weeks. Patients were allocated into groups according to the presence of clinical or endoscopic disease activity. Serum ADA concentrations were measured and compared between groups. Overall, 89 patients were included. A total of 27 patients had clinically active CD and 62 were in clinical remission. Forty patients had endoscopic disease activity and 49 were in endoscopic remission. The mean serum ADA concentration was 10.2 μg/mL in patients with clinically active CD and 14.3 μg/mL in patients in clinical remission (p = 0.395). The mean serum ADA concentration in patients with endoscopic activity was 11.3 μg/mL as compared to 14.5 μg/mL in those with endoscopic remission (p = 0.566). There was no difference between serum ADA concentrations regarding clinical or endoscopic activity in CD, as compared to patients in remission.

P596 Adalimumab use in Paediatric Inflammatory Bowel Disease: A single centre real-life experience

Abstract Background Anti-TNF-α, including infliximab and adalimumab (ADA), plays a crucial role in the treatment of Paediatric Inflammatory Bowel Disease (PIBD). This study evaluates the efficacy of ADA in children ≤ 19 years in a single European centre. Methods A 6-year retrospective analysis of prospectively collected data of PIBD patients treated with ADA (10/2015 onward). Wellbeing, clinical and laboratory findings were assessed at each visit. A mean, median and a standard deviation were calculated were applicable. ANOVA (analysis of variances) was used for evaluation of presence of statistically significant differences and a P-value ≤ 0.05 was regarded as such. Results ADA, all originator, was used in 31 patients. All of them were diagnosed with Crohn’s Disease (CD). The mean age at diagnosis was 14.6±2.8 years (range 6.6–18.2 years). The mean interval from diagnosis till commencement of ADA was 6.9 months (0.25–36 months). Step-up was used 17x and top-down 15x. A top-down approach was indicated in patients with extraintestinal manifestations, fistulizing disease, severe growth impairment and affections of the proximal gastrointestinal tract. Adjacent treatments at the time of commencement of ADA were azathioprine (18/31), CD exclusion diet (7/31), exclusive enteral nutrition (6/31), steroids (4/31), methotrexate and 5-aminosalicylates (both 3/31). Mean CRP at the time of ADA commencement was 8.8 mg/l (1.0–44.4 mg/l), ESR 21 mm/hour (1–66 mm/hour), leukocytes 8.3x109/l (3.3–22.0x109/l), haemoglobin 118.3 g/l (68–150 g/l), platelets 422x109/l (232–828 x109/l) and faecal calprotectin (FC) 901.1 μg/g (95.2–5041.9 μg/g). At the end of induction period, CRP, ESR and FC showed a significant decrease (P< 0.01). Blood count parameters failed to show that (P >0.05). Mean ADA trough levels at the end of induction period were 18.4±2.3 μg/ml. For maintenance of trough levels (≥7.5 μg/ml), weekly administration was required in 5 cases. During the follow-up period, surgical intervention was required 2x (ileocecal resection 1x and stricturoplasty 1x). Adverse side effects consisted of a skin reaction 1x and reversible hair loss 1x. Due to loss of response, 3 patients had to be switched out-of-class to ustekinumab. The mean time to loss of response since ADA commencement was 23.3 months (16–30 months). Antibody formation after 23 months of treatment led to switching one patient to infliximab. One patient was lost to follow-up. Conclusion These data show that ADA is effective in achieving laboratory and clinical remission in PIBD patients. Maintenance of trough levels may sometimes requite weekly administration of ADA. Loss of response may occur. Adverse reactions were minimal.

Adalimumab Concentration Changes After Dose Escalation in Inflammatory Bowel Disease.

Dose escalation of adalimumab (ADA) for loss or response in inflammatory bowel disease (IBD) is a common practice. Recent data suggest improved outcomes with an ADA concentration of 12 mcg/mL, but limited data are available on the ability to achieve a target concentration. The aim of this study was to determine the expected change in serum ADA concentration after a dose escalation performed every 7 days in patients with IBD. A retrospective cohort of patients with IBD receiving ADA was divided into every fourteen-day dosing, every 7-day dosing, and dose escalation (ie, q14 to q7 day dosing). The primary outcome was the change in ADA concentration. Multiple logistic regression was performed to identify predictors of achieving a target ADA concentration of ≥12 mcg/mL. Overall, 380 patients were identified, of whom 200 underwent dose escalation, 100 remained on q14 days dosing, and 80 were maintained on q7 day dosing. After dose escalation, the mean ADA concentration increased by 5.5 mcg/mL (P < 0.0001). After dose escalation, a significant proportion of patients achieved an ADA concentration ≥12 mcg/mL (P = 0.0019), as well as clinical remission (P = 0.0053). Based on multiple logistic regression, age of <46 years [odds ratio (OR): 2.4; 95% confidence interval (CI): 1.3, 4.6; P < 0.01], body mass index of <29 (OR: 0.21; 95% CI: 0.1, 0.5; P < 0.0001), and initial ADA concentration of ≥3.0 mcg/mL were found to be associated with a target ADA concentration ≥12 mcg/mL (OR: 4.76; 95% CI: 2.3, 9.7; P < 0.0001). The average expected increase in serum ADA concentration after dose escalation from q14 to q7 days was 5.5 mcg/mL. The initial ADA concentration, age, and body mass index may influence the ability to achieve a target ADA concentration after dose escalation.

FRI0295 ADALIMUMAB LEVELS ARE ASSOCIATED WITH DRUG RETENTION RATES IN AXIAL SPONDYLOARTHRITIS PATIENTS

Background:Production of anti-drug antibodies (ADA) could cause low serum anti-TNF levels and low drug retention rates.Objectives:To assess the relationship between serum adalimumab (ADL) levels and drug retention rates in patients with axial SpA.Methods:Single-center prospective study in patients with axial SpA, according to ASAS criteria, being treated with ADL. In the first part of the study, from December 2010 to June 2016, data was collected and serum samples were taken. In a second part of the study, clinical records were reviewed to find out the dates and reasons of treatment discontinuation. Information was collected on age gender, body mass index (BMI), date of diagnosis of SpA, laboratory data, including HLAB27, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), prior biological treatment for SpA, concomitant conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). SpA disease activity was assessed by BASDAI, ASDAS and PGA scores. A serum sample was taken from all patients just before the next adalimumab dose. ADL and ADA levels were analysed with ELISA Promonitor®, (Proteomika, Progénica, Griffols) and correlated with SpA activity using BASDAI and ASDAS scores. Cox proportional hazards model was performed in order to assess the relation of variables with drug interruption.Results:Up to January 2016, 51 consecutive patients were included. The mean (range) age was 46,9 (18–68) and 47.1% were women. HLAB27 was positive in 82,4% of patients. Mean disease duration was 122,9 months (2-408) and mean duration of treatment with adalimumab was 17,8 months (1-69). ADL was the first biological agent received in 36 patients (70.6%). Eleven patients (21.6%) were on concomitant treatment with receiving concomitant csDMARDs, mainly methotrexate (MTX) (15.7%) and sulfasalazine (5.9%). The mean (SD) activity scores were BASDAI 4,0 ± 2,3; ASDAS-PCR 2,1 ± 1,1 and ASDAS-VSG 2,1 ± 1,0.ADA prevalence was 27.5%, with none detected in the 21.6% taking csDMARDs (p = 0.021). ADL level was normal (&gt; 3 mg/l) in 36 patients (70.6%), all without ADA. Fifteen patients (29.4%) had subtherapeutic ADL levels (&lt; 3 mg/l), with ADA in 14 (93%).Total ADL treatment time was 241,16 patient/years, and mean ADL treatment time was 4,73 years. Cox model results were resumed in table 1. Multivariate study show that ADL level &gt; 3 mg/L was a protective factor for ADL interruption (HR 0.01 (0.00-0.59, p=0.026), while previous etanercept treatment was a risk factor for ADL interruption 9.54 (1.23-74.08, p=0.031).Table 1.Cox model.ContinueDiscon=tinueUnivariateHRMultivariateHRADL level&lt;3 mg/L13 (86,7%)2 (13,3%)0.05 (0.00-0.65, p=0.022)0.01 (0.00-0.59, p=0.026)≥3 mg/L28 (77,8%)8 (22,2%)Concomitant DMARDYes8 (72,7%)3 (27,3%)0.56 (0.14-2.26, p=0.419)0.28 (0.05-1.65, p=0.159)No33 (82,5%)7 (17,5%)BMINormal13 (86,7%)2 (13,3%)2.56 (0.54-12.23, p=0.239)0.48 (0.02-9.75, p=0.634)Overweight/obese27 (77,1%)8 (22,9%)AgeMean (SD)46,4 (12,2)48,7 (11,6)0.93 (0.24-3.60, p=0.912)0.60 (0.10-3.84, p=0.594)GenderMen19 (70,4%)8 (29,6%)0.43 (0.09-2.03, p=0.283)0.58 (0.03-10.06, p=0.705)Women22 (91,7%)2 (8,3%)InfliximabpreviousYes4 (40,0%)6 (60,0%)3.31 (0.92-11.87, p=0.066)1.37 (0.23-8.24, p=0.731)No37(90,2%)4 (9,8%)EtanerceptpreviousYes2 (22,2%)7 (77,7%)8.17 (2.09-31.90, p=0.003)9.54 (1.23-74.08, p=0.031)No39 (92,9%)3 (7,1%)ADL: adalimumab; BMI: body mass index; DMARD: disease modifying antirheumatic drug; SD: standard deviation.Conclusion:Adalimumab drug levels &gt; 3 mg/L is a protective factor against treatment interruption.Etanercept previous treatment was a risk factor for treatment interruption.Acknowledgments:The study was supported by a grant from “Asociación para la Investigación en Reumatología de la Marina Baixa” (AIRE-MB).Disclosure of Interests:None declared

746 Adalimumab Concentrations Following Dose Escalation in Inflammatory Bowel Disease

INTRODUCTION: Therapeutic drug monitoring is frequently performed for the management of inflammatory bowel disease (IBD). Adalimumab (ADA) concentrations of 12-16 ug/ml have been associated with clinical and endoscopic remission in Crohn's disease (CD) and ulcerative colitis (UC). The feasibility of achieving these concentrations following a dose escalation is unknown. We aim to determine expected rise in serum ADA concentrations in response to increased dose frequency. METHODS: Patients with an established diagnosis of IBD, on maintenance ADA therapy, and two ADA trough concentrations were included. The primary outcome was change in ADA concentration following dose escalation from every other week to weekly. Patients who had two concentrations without a dose escalation served as a control. Student's t-test was used to assess for significant differences in and between patients. Exploratory logistic regression was used to assess for clinical factors predicting the ability to achieve an ADA concentration &gt;12 ug/ml. RESULTS: Eighty-nine patients met inclusion criteria, 71% with CD, 23% with UC, and 6% with indeterminate colitis. Thirty six percent were on concurrent immunomodulator (IMM) therapy. Among patients on every other week ADA dosing, the initial mean ADA concentration for those who went on to a dose escalation was 3.7 ug/ml versus 9.7 ug/ml in those who did not dose escalate (P &lt; 0.001). Following dose escalation, mean ADA concentration significantly increased by 5.7 ug/mL (P &lt; 0.0001) compared to a significant decrease of 2.5 ug/mL (P &lt; 0.002) in those who remained on every other week dosing. This decrease was driven by IMM de-escalation (mean decrease of 1.7 ug/ml in those without IMM change, versus 5.5 ug/ml in those who stopped IMM, P &lt; 0.1). Exploratory logistic regression analysis identified initial ADA concentration, female sex, and ADA as first biologic as predictors of achieving an ADA concentration &gt;12 ug/ml after dose escalation. CONCLUSION: Among patients with an initial low ADA concentration, a dose escalation to weekly will increase the concentration by 5.7 ug/ml on average. Without dose escalation, cessation of IMM may decrease ADA concentrations by 5.5 ug/ml. Female sex, ADA as first biologic, and initial ADA concentration of ≥4.9 ug/ml all predicted the ability to achieve a concentration of &gt;12 ug/ml following dose escalation. The expected concentration change after ADA dose escalation can help to guide treating physicians in determining when dose escalation is appropriate.

P066 The relationship between serum adalimumab and corresponding anti-adalimumab antibody levels: analysis of over 20,000 patient results

BACKGROUND: Adalimumab (ADL) is a TNF inhibitor administered by injection. Serum assays of ADL and its anti-drug antibodies (ADAb) are utilized to manage failure to respond and loss of response. These monitoring assays may also be used to proactively titrate doses and dosing intervals (1). Here, 22,012 adalimumab (ADL) patient results were analyzed. METHODS: Measurements of drug and ADAb levels were performed by lab developed chemiluminescent immunoassays (2). The lower limits of quantitation are 0.6 μg/mL for adalimumab and 25 ng/mL for anti-adalimumab antibodies. Drug assays measure free (ADAb-unbound) drug while ADAb assays detect total antibodies (including IgM and IgG subtypes) and are drug- tolerant to the presence of up to &gt;20 μg/mL of drug. Clinical histories and blood collection timing are unknown. RESULTS: Of 22,012 measured adalimumab samples, 60% (13,176) were ADAb-free and 40% (8,836) had measurable anti-adalimumab antibodies. Of all ADAb-free samples, the majority (10,171 or 77%) had ADL concentrations between 3 and 30 μg/mL while drug levels were &lt;3 μg/mL in 2,495 (19%). Of ADAb-positive samples, most were positive in the low to intermediate titer range (25 to 200 ng/mL) Furthermore, as ADAb increase, their corresponding mean drug concentrations diminish. Low concentrations of ADAb (&lt;100 ng/mL) appear to have minimal impact on mean drug levels where the baseline mean adalimumab (6.1 μg/mL) was calculated from 11,085 ADAb-free samples with adalimumab from 0.6 to 15 μg/mL. ADAb titers between 100 and 300 ng/mL are associated with a moderately diminished mean adalimumab (3.4–5.6 μg/mL) while high ADAb titers (&gt;300 ng/mL) are invariably associated with diminished free ADL concentrations &lt;30% of the mean. CONCLUSION(S): Of 22,012 samples, 60% were ADAb-free. Of those, about one third (37%) were within the target range of 5–10 μg/mL for adalimumab while 36% of samples were subtherapeutic at &lt;5.0 μg/mL. Anti-adalimumab antibodies occurred in 40% of samples, and ADL drug concentrations were inversely related to anti-adalimumab antibody titers where low titer ADAb may have little or no impact on free drug levels while high titer ADAbs are associated with very diminished or absent drug. These findings are consistent with American Gastroenterological Association Critical Care Pathways for Crohn's Disease and Ulcerative Colitis where low and high antibody scenarios are managed very differently. It may be possible to treat away low titer ADAb by increasing drug or adding an immunomodulator (3). Therefore, drug-tolerant anti-drug antibody assays that have been designed both (1) to detect low level ADAb and (2) to distinguish low to intermediate to high titers with high resolution (from 25 to 2,000+ ng/mL) may be most helpful in preventing, managing and treating immunogenicity.

P045 Do Levels Matter? Maintaining Anti-TNF Class After Secondary Loss of Response to Adalimumab in Inflammatory Bowel Disease

BACKGROUND: Anti-tumor necrosis factor (Anti-TNF) biologic therapies have evolved as a mainstay of treatment for inflammatory bowel disease (IBD). However, 10%–20% of patients are primary non-responders to anti-TNF in clinical series and up to 40% of patients lose response to treatment over time. Current guidelines suggest that treatment failure in the setting of adequate drug concentrations are due to mechanistic failure and should be switched out of the anti-TNF class. Our aim was to assess the efficacy of switching to infliximab, rather than changing out of class, in patients with secondary loss of response to adalimumab who had a therapeutic drug level. METHODS: A retrospective chart review identified patients with ulcerative colitis (UC) and Crohn's disease (CD) treated with adalimumab within the University of North Carolina Inflammatory Bowel Disease clinic between January 1, 2007 and December 31, 2017. Patients with a therapeutic adalimumab level and treatment failure and who were subsequently treated with infliximab were included in the study. RESULTS: There were a total of 16 patients with therapeutic adalimumab levels (&gt;5 μg/mL) and no antibody formation with treatment failure. In this population, 11 of the patients had CD, 3 patients had inflammatory bowel disease undifferentiated (IBDU) and 2 had UC. Ileocolonic CD (45.5%) and penetrating disease (54.4%) were the most common phenotypes. All patients had secondary loss of response to adalimumab and 87.5% had been increased to weekly dosing. Mean adalimumab level was 9.8 ± 6.8 μg/mL prior to switching to infliximab. Thirteen patients (81.3%) achieved clinical response with infliximab at 14 weeks and of the 8 patients with endoscopic assessments, 100% achieved endoscopic remission (5 with UC/IBDU and 3 with CD). There were a total of 6 patients in a sensitivity analysis assessing therapeutic levels &gt;7 μg/mL. All patients were female, however all other characteristics in this group were similar to those patients evaluated with a therapeutic threshold of 5 μg/mL, including the rate of clinical response at 14 weeks (83.3%). When compared to 28 patients with adalimumab levels &lt;5 μg/mL, there was no significant difference in clinical response at 14 weeks (P = 0.692). CONCLUSION(S): Switching within class to infliximab after secondary loss of response to adalimumab with a therapeutic level achieved clinical remission at 14 weeks in 81.3% of patients, and appears to be an acceptable strategy in selected patients. Therapeutic drug levels alone are not predictive of clinical response to a second anti-TNF.

Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease

To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.

Methotrexate Dose in Patients With Early Rheumatoid Arthritis Impacts Methotrexate Polyglutamate Pharmacokinetics, Adalimumab Pharmacokinetics, and Efficacy: Pharmacokinetic and Exposure-response Analysis of the CONCERTO Trial

PurposeMethotrexate (MTX) and adalimumab are well-recognized treatments of rheumatoid arthritis (RA), the efficacy of which may be driven by intracellular polyglutamates (PGs). The aim of this analysis was to characterize MTX PG concentrations and adalimumab pharmacokinetics in the CONCERTO trial. In addition, the relationships between MTX dose/pharmacokinetics, adalimumab pharmacokinetics, and efficacy were evaluated. MethodsCONCERTO was a double-blind, parallel-arm study in patients with early RA randomized to adalimumab 40 mg SC every other week plus blinded MTX 2.5, 5, 10, or 20 mg PO once weekly, for 26 weeks. Blood samples were obtained through week 26 for the determination of concentrations of MTX PG, adalimumab, and anti-adalimumab antibody (AAA). Clinical outcomes were also assessed. FindingsA total of 395 patients were included in the analysis (MTX, 329; adalimumab, 395). The mean time to steady-state MTX PG concentration was increased with MTX dose, from 8 to >26 weeks, depending on PG chain length. Dose proportionality changed with PG chain length. As MTX dose was increased, the percentage of short-chain PGs increased less than dose proportionally, while the percentage of long-chain PGs increased more than dose proportionally. For very-long-chain PGs, dose proportionality could not be assessed due to the nonmeasurable concentrations in the 2.5- and 5-mg MTX dose groups. As MTX dose increased, mean adalimumab concentrations also increased (P < 0.001). The percentage of patients with AAA decreased with increasing MTX dose, and at week 26, AAA+ status was significantly correlated with MTX dose level (P = 0.005). In general, rates of response, defined using the 28-joint count disease activity score based on C-reactive protein (DAS28[CRP]; response, <3.2), were greater in the subgroup without AAA. The likelihood of a patient achieving a DAS28(CRP) response was related to the baseline measurement (P < 0.001) and to the concentration of adalimumab (P = 0.001), but not to the MTX regimen (P = 0.689). ImplicationsThe dose–response characteristics of MTX PG pharmacokinetics and the resultant effects of MTX on adalimumab exposures should be considered when determining the benefit–risk profile of MTX and adalimumab combination therapy in patients with early RA. ClinicalTrials.gov identifier: NCT01185301.

One-Year Clinical Outcomes in an IBD Cohort Who Have Previously Had Anti-TNFa Trough and Antibody Levels Assessed.

Loss of response (LOR) is a big concern for anti-TNFa therapies in inflammatory bowel disease. Immunomonitoring may be useful to optimize response rates and overcome secondary LOR. This was an observational retrospective cohort study of a group of patients with inflammatory bowel disease on infliximab (IFX) and adalimumab (ADA) who had anti-TNFa trough and antibody levels measured, during maintenance phase of treatment. Anti-TNFa trough and antibody levels were measured using standard enzyme-linked immunosorbent assay techniques. Baseline patient characteristics were determined and patients were reviewed 1 year later. Clinical assessment took place with partial Mayo scores for ulcerative colitis and Harvey-Bradshaw index for Crohn's disease. C-reactive protein (CRP) and albumin were also measured. Poor outcomes were defined as the following: need for rescue steroids, dose intensification, surgery, or treatment discontinuation. Seventy-four patients were included in the study, 37 (50%) were female, mean age 41 years, 61 (82%) had Crohn's disease, and 42 (57%) ulcerative colitis. Forty-two (57%) patients received IFX and 32 (43%) ADA. Mean IFX trough was 3.6 μg/mL and mean ADA troughs were 3.78 μg/mL. Twenty-seven percent of patients (n = 20) overall had a poor outcome, with a similar proportion in each group 24% (n = 10) IFX and 31% (n = 10) ADA (P value 0.24). Of the cohort, 14.2% (6/42) treated with IFX had subtherapeutic trough levels, 6.2% (2/32) of ADA patients had a trough level <1 μg/mL (P value = 0.273) There was no difference in mean trough according to outcome (4.9 μg/mL poor versus 5.4 μg/mL good, P value 0.14). Low IFX trough levels did correlate with high CRP, low albumin and response rates, mean CRP 6.66 μg/mL (n = 3), mean albumin 37 g/L for patients with low trough levels and poor response versus CRP 2.0 μg/mL (n = 24), mean albumin 43 g/L for patients with high trough levels and good response (P = 0.009, 95% confidence interval, -0.78 to -0.12). LOR is still a big concern with anti-TNFa therapies. Stand-alone anti-TNFa trough and antibody levels are not useful at predicting LOR/disease progression at 1 year, but low trough levels do correlate well with elevated CRP, hypoalbuminaemia, and poor response rates.

PTU-049 Concurrent Immunomodulator Therapy does not Influence Infliximab or Adalimumab Trough Levels During Maintenance Therapy

Introduction Combination therapy with infliximab (IFX) and immunomodulators (IM) is superior to monotherapy showing better outcomes at 1 year for Crohn’s disease 1 and UC. 2 Withdrawal of IM after 6 months of combination therapy has been shown not to adversely affect clinical outcomes though patients on concurrent thiopurine have higher trough levels and lower CRP. 3 The role of concomitant IM therapy is unclear for patients treated with adalimumab (ADA). We aimed to evaluate the impact of concomitant IM therapy on trough levels of IFX and ADA. Methods We conducted a retrospective observational study of all IBD patients on maintenance therapy who had had IFX and ADA trough levels measured between Jan13-Jan16. Testing was undertaken at the discretion of the treating clinician. Clinical information including duration of disease, site of disease, duration of anti-TNF therapy, IM therapy, smoking status, prior anti-TNF exposure, and disease activity was recorded. Drug level and anti-drug antibody measurements were performed on sera using the Lisa-Tracker IFX and ADA ELISA kit (Theradiag, France). Pairwise comparison of means was used to compare trough levels in patients with and without concomitant IM therapy. A multivariate logistic regression was used to correct for confounders and the impact on antibody formation assessed with Fishers exact test. Results 200 patients (120 IFX and 80 ADA) were included. 65.8% of IFX and 55% of ADA patients were on concurrent IM therapy. Mean ADA trough levels among patients on concurrent IM was 6.72±1.91µg/ml whilst patients not on concurrent IM had levels of 5.16±2.88 µg/ml(p = 0.005). This difference was not significant after adjustment for dose escalation. 23 patients (28.7%) were on weekly dosing whereas 57 (71.2%) were on alternate weeks. The mean trough level in patients on IM was 4.01±3.52 and not on IM was 3.96±2.83(p = 0.9). Thirty patients had positive antibodies and trough levels were 1.25±2.1µg/ml compared to 4.91±3.1µg/ml(p Conclusion Trough levels of IFX and ADA were not significantly different among maintenance patients with and without concomitant IM therapy. Surprisingly, the immunogenicity of IFX was not impacted by concurrent IM. References 1 Ruffolo C, et al . Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 2010; 363 :1086–8. 2 Panaccione R, et al . Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology 2014; 146 :392–400. 3 Drobne D, et al . Withdrawal of immunomodulators after co-treatment does not reduce trough level of infliximab in patients with crohn’s disease. Clin Gastroenterol Hepatol 2015; 13 :514–21. Disclosure of Interest None Declared

The clinical relevance of early anti-adalimumab antibodies detection in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: A prospective multicentre study

ObjectivesTo evaluate the relevance of anti-adalimumab (anti-ADA) antibodies (Abs) and their relationship with clinical/laboratory features in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). MethodsFifty-eight patients affected with RA, AS and PsA were prospectively enrolled. Clinical/laboratory characteristics, disease activity, anti-ADA, anti-nuclear (ANA), anti-double strand (ds)DNA, anti-extractable nuclear antigens (anti-ENA) and anti-phospholipid Abs (aPL) were evaluated at baseline, 4, 12 and 24 weeks of adalimumab treatment. ResultsAnti-ADA Abs were observed in 11/58 (19%) patients; they were detected within the 4th week of therapy in 90.9% of the positive subjects. Anti-ADA positivity was associated with significantly lower mean adalimumab serum levels (P<0.05). Treatment failure was observed in 20/58 (34.5%) patients and was significantly associated with anti-ADA Abs (P<0.05). Mean adalimumab serum levels were significantly lower in patients with treatment failure than in the responders one, both in the whole cohort (P<0.01) and in the group of anti-ADA positive patients (P<0.01). Adverse events happened more often in anti-ADA positive then in anti-ADA negative patients (27.3% vs 14.9%). ConclusionsAnti-ADA abs could be considered an early marker associated to a poor clinical response to adalimumab treatment. Routine ANA/anti-ENA/aPL monitoring did not reveal as useful tools to predict the development of anti-ADA abs.

OP0074 A Concentration-Effect Curve of Adalimumab in Patients with Psoriatic Arthritis

BackgroundIn rheumatoid arthritis the concentration-effect relationship of adalimumab has been investigated.[1] However, in psoriatic arthritis (PsA) there is a lack of knowledge about the pharmacodynamics and pharmacokinetics of adalimumab.ObjectivesTo investigate...

OP0067 Efficacy, Pharmacokinetics, and Safety of Different Doses of Methotrexate in Combination with Adalimumab: Results from the Concerto Trial

BackgroundAnti-TNF plus methotrexate (MTX) is more effective than either as monotherapy. Thus far, no controlled data are available on the benefit:risk of different doses of MTX in combination with anti-TNF.ObjectivesTo...

A multicenter, open-label, efficacy, pharmacokinetic, and safety study of adalimumab in Japanese patients with ankylosing spondylitis

We evaluated the efficacy, pharmacokinetics, and safety of adalimumab in Japanese patients with active ankylosing spondylitis (AS) who had an inadequate response to, or who were intolerant of, treatment with ≥1 nonsteroidal anti-inflammatory drugs (NSAIDs). This phase 3, multicenter, open-label trial assessed the percentage of patients with a 20% response in the Assessment of SpondyloArthritis international society working group criteria (ASAS20) at week 12 as the primary endpoint. Secondary outcome measures included assessments of disease activity, clinical response, functionality, and spinal mobility at weeks 12 and 60. Serum trough adalimumab concentrations were summarized using descriptive statistics. The adverse event profile was summarized for patients who received at least one dose of the study drug during the assessment period. At week 12, 73.2% (30/41) achieved an ASAS20 response and nearly 40% met ASAS partial remission criteria; proportions were maintained after up to 60 weeks of therapy. Mean adalimumab concentrations reached steady-state between weeks 12 and 20. Adalimumab was generally safe and well tolerated, with approximately 90% of adverse events considered to be mild. These results support the use of adalimumab as a safe and effective therapy for Japanese patients with active AS.

A multicenter, open-label, efficacy, pharmacokinetic, and safety study of adalimumab in Japanese patients with ankylosing spondylitis

We evaluated the efficacy, pharmacokinetics, and safety of adalimumab in Japanese patients with active ankylosing spondylitis (AS) who had an inadequate response to, or who were intolerant of, treatment with ≥1 nonsteroidal anti-inflammatory drugs (NSAIDs). This phase 3, multicenter, open-label trial assessed the percentage of patients with a 20% response in the Assessment of SpondyloArthritis international society working group criteria (ASAS20) at week 12 as the primary endpoint. Secondary outcome measures included assessments of disease activity, clinical response, functionality, and spinal mobility at weeks 12 and 60. Serum trough adalimumab concentrations were summarized using descriptive statistics. The adverse event profile was summarized for patients who received at least one dose of the study drug during the assessment period. At week 12, 73.2% (30/41) achieved an ASAS20 response and nearly 40% met ASAS partial remission criteria; proportions were maintained after up to 60 weeks of therapy. Mean adalimumab concentrations reached steady-state between weeks 12 and 20. Adalimumab was generally safe and well tolerated, with approximately 90% of adverse events considered to be mild. These results support the use of adalimumab as a safe and effective therapy for Japanese patients with active AS.