Serum trough levels of infliximab are not associated with peripheral arthralgia activity in patients with inflammatory bowel disease

BackgroundInfliximab is an efficacious therapy for inflammatory bowel disease and may play a role in management of some extraintestinal manifestations. While higher trough levels of infliximab are associated with higher rates of disease remission, the association between trough levels of infliximab and arthralgia activity characterised as an extraintestinal manifestation has yet to be defined.ObjectiveWe aimed to assess the association between serum trough levels of infliximab and peripheral arthralgia activity in patients with inflammatory bowel disease.DesignIn this cross-sectional study, we identified patients with inflammatory bowel disease on infliximab therapy with known history of arthralgias attributed to an extraintestinal manifestation. Collected variables included disease phenotype, medications (such as thiopurines or methotrexate), Harvey Bradshaw Index, partial Mayo score, C reactive protein, trough levels of infliximab and anti-infliximab antibodies. The primary outcome was active patient-reported arthralgia.ResultsOut of 267 patients included, 65 (24.4%) had active arthralgias at the time the trough level of infliximab was measured. No significant differences in trough levels were seen between those patients with and without arthralgias. Patients on combination therapy with methotrexate or thiopurines or those with detectable anti-infliximab antibodies were not more likely to have inactive arthralgias (OR 0.99, 95% CI 0.57 to 1.74, p=0.99 and OR 1.94, 95% CI 0.9 to 4.1, p=0.09, respectively).ConclusionsThis study suggests that although therapeutic drug monitoring of infliximab can have a role in the management of Crohn’s disease and ulcerative colitis, it does not seem to be useful in managing arthralgias associated with inflammatory bowel disease.

Effectiveness and Safety of Nonmedical Switch From Adalimumab Originator to SB5 Biosimilar in Patients With Inflammatory Bowel Diseases: Twelve-Month Follow-Up From the TABLET Registry

BackgroundFew data are currently available about SB5 in inflammatory bowel diseases (IBD). The aim of this study was to assess the effectiveness and safety of SB5 in a cohort of patients with IBD in stable remission switched from the adalimumab (ADA) originator and in a cohort of patients with IBD naïve to ADA.MethodsWe prospectively enrolled patients with IBD who started ADA treatment with SB5 (naïve cohort) and those who underwent a nonmedical switch from the ADA originator to SB5 (switching cohort). Clinical remission and safety were assessed at baseline and at 3, 6, and 12 months. In addition, in a small cohort of patients who were switched, we assessed the ADA serum trough levels and antidrug antibodies at baseline, 3, and 6 months.ResultsIn the naïve cohort, the overall remission rate at 12 months was 60.42%, whereas in the switching cohort it was 89.02%. Fifty-three (36.3%) patients experienced an adverse event, and injection site pain was the most common; it was significantly more frequent in the switching cohort (P = 0.001). No differences were found in terms of ADA serum trough levels at baseline, 3, and 6 months after switching. No patient developed antidrug antibodies after the switch.ConclusionsWe found that SB5 seemed effective and safe in IBD, both in the naïve cohort and in the switching cohort. Further studies are needed to confirm these data in terms of mucosal healing.

CTNI-52. PHASE II STUDY OF EVEROLIMUS (AFINITOR®) FOR CHILDREN WITH RECURRENT OR PROGRESSIVE EPENDYMOMA

Preclinical studies suggested that the mTOR signaling pathway could be a potential therapeutic target in childhood ependymomas. As a result, a phase II clinical trial (ClinicalTrials.gov identifier: NCT02155920) of single-agent everolimus was performed to test the hypothesis that inhibition of the mTOR pathway would result in tumor responses for children with recurrent and/or progressive ependymoma. Eleven patients [sex: 4 females (36.4%); median age: 8 years (range: 2 – 15 years); race: 9 white and 2 other; prior therapies: median 6 (range: 3 – 9)] were enrolled on the study. The primary tumor location for 10 participants was the posterior fossa; the primary location of the remaining tumor was the cervical spine. All patients were treated with oral everolimus 4.5 mg/m2/day (each cycle = 28 days) that was titrated to achieve serum trough levels of 5 – 15 ng/mL. Overall, everolimus was well tolerated; adverse events were grade 1 – 2 and consistent with its previously established safety profile in children. No objective tumor responses were observed. All patients discontinued therapy due to tumor progression after a median of 2 cycles of therapy (1 cycle = 2; 2 cycles = 6; 3, 4, and 8 cycles = 1 each). This study does not support the use of everolimus for children with recurrent or progressive ependymoma.

FRI0042 DISCREPANCIES BETWEEN RAPID3 AND DAS28 IN RHEUMATOID ARTHRITIS PATIENTS IN REMISSION OR LOW DISEASE ACTIVITY RECEIVING TNF INHIBITORS: WHAT IS THE ROLE OF THE INFLAMMATION BIOMARKERS?

Background:Patients and Rheumatologist often differ in their perception of RA disease activity. Remission or low disease activity should be the treatment target in RA, patients should be included in treatment decisions.Objectives:To identify factors influencing patient’s self-reported disease activity by RAPID3 test.Methods:47 RA patients in remission or low disease activity by DAS28ESR (DAS28ESR ≤ 3.2) receiving TNFi (etanercept, adalimumab and infliximab) stratified their disease activity by RAPID3, then two patients’ groups were defined:target group(RAPID3 with remission 0-3 or low disease activity 3.1-6),non-target group(RAPID3 with moderate 6.1-12 or high disease activity >12). Demographic data, disease duration, autoantibody status, radiological data, concomitant csDMARD therapy was collected. Laboratory measurements included CRP, ESR, calprotectin serum levels, TNFi trough serum levels, and antidrug antibodies (enzyme-linked immunosorbent assay (ELISA) test kit (Calprolab™ Calpro AS, Oslo, Norway, and Promonitor®, Progenika SA, Spain, respectively) according to the manufacturers’ protocol. Pearson´s correlations coefficients were used to identify variables correlating with RAPID3 score. Mixed-effects analyses of covariance (ANCOVAs) models were used to identify factors influencing RAPID3 score.Results:Patients in “target group”have shown a significant lower TJC, pain by VAS 0-10mm, and calprotectin serum levels, but higher TNFi serum trough levels in comparison to “non-target group”. When patients were classified according to RAPID 3 categories, patients in “remission” have shown lower calprotectin serum levels than those classified as in “high disease activity” (0.94 (4.88-0.14) vs. 4.57 (7.97-1.25),p=0.001, respectively). Accordingly, when classified according to pain by VAS 0-10mm, patients with low levels of pain had lower calprotectin serum levels vs. those with severe pain (1.43 (6.33-10.14) vs. 5.16 (8.80-1.25),p=0.009, respectively). When distributed according to PGA (1=very good, 2=good, 3=regular, 4=bad, 5=very bad) patients in “very good” group had lower mean of calprotectin serum levels than those in “very bad” group (0.94 (4.88-0.14) vs. 4.57 (7.97-1.25),p=0.001, respectively). PGA and Pain VAS have shown a strong correlation with RAPID 3 (R20.978, and 0.834,p=0.001, respectively), while calprotectin and TNFi serum trough levels showed a moderate correlation (R20.311, and 0.372,p=0.005, respectively). The multivariate adjusted analysis showed a significant association between Pain and RAPID3 (p<0.001) according to the different covariates (age, gender, anti-CCP positivity, time in remission, SJC, TJC, DAS28ESR). In addition, calprotectin and TNFi trough serum levels were associated with RAPID 3 (p<0.005). Backward selection of variables did not substantially modify the association between RAPID 3 and pain, calprotectin and TNFi trough serum levels.Conclusion:61.7% of RA patients undergoing TNFi classified as in remission or low disease activity by DAS28ESR, self-reported their disease activity as moderate or high by RAPID3. The most significant factor influencing patient’s perception of disease activity is pain (pain VAS and TJC). However, inflammation markers (calprotectin, TNFi serum trough levels) remain statistically significant after fully adjustment by different confounders. Thus, therapies improving these three domains will have a larger impact in patient´s perception of disease activity.References:[1]Studenic P, et al. Arthritis Rheum. 2012;64:2814-23.Disclosure of Interests:Jose Inciarte-Mundo Employee of: Eli Lilly, Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Rosa Morlà Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Beatriz Frade-Sosa: None declared, Julio Ramírez Speakers bureau: Abbvie, Eli Lilly, BMS, Roche, Novartis and Pfizer, Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Virginia Ruiz Speakers bureau: Lilly, Pfizer, Juan de Dios Cañete: None declared, José Gomez Puerta Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer