Therapeutic monitoring of adalimumab at non-trough levels in patients with inflammatory bowel disease.

Adalimumab (ADA) trough level and anti-ADA antibody (AAA) positivity influence mucosal healing and loss of response in patients with inflammatory bowel disease (IBD). In this study, we clarified the correlation between ADA monitoring, including non-trough level, and real-world IBD clinical outcomes. This retrospective, observational, single-center study involved patients with ulcerative colitis (19) and Crohn's disease (33) treated with ADA from January 2007 to August 2018. Serum ADA and AAA levels were measured 4‒14 days after ADA administration. The AAA positivity rate was 23.1% (12/52). ADA continuity was higher in AAA-negative patients than in AAA-positive patients (P = 0.223). Receiver operating characteristic (ROC) analysis revealed that a serum AAA cut-off of 9.2 µg/mL was associated with ADA continuity. The ADA level was significantly higher in the endoscopic remission group than in the non-remission group (P = 0.02). Based on the ROC curve analysis results of serum ADA level and endoscopic remission, the cut-off value of the serum ADA level was set to 11.1 µg/mL. Under the combined use of ADA with immunomodulators and AAA positivity, ADA continuity was significantly higher when the serum AAA level at 4-14 days after ADA administration was ≥9.2 µg/mL. Furthermore, endoscopic remission can be expected with a serum ADA level of ≥11.1 µg/mL. Overall, to predict clinical outcomes, it would be useful to measure the blood level of ADA regardless of the timing of the trough.

Highly Bioavailable Curcumin Derivative Ameliorates Crohn's Disease Symptoms: A Randomized, Double-Blind, Multicenter Study.

BACKGROUND & AIMS: The new curcumin derivative Theracurmin® has a 27-fold higher absorption rate than natural curcumin powder. Theracurmin® is an inhibitor of nuclear factor-κB, which mediates the expression of inflammatory cytokines. The effect of Theracurmin® on inflammatory bowel disease in humans has not been explored; therefore, we investigated the efficacy and safety of Theracurmin® in patients with Crohn's disease. METHODS: In this randomized, double-blinded study performed at 5 independent medical centers in Japan, Theracurmin® (360 mg/day, n = 20) or placebo (n = 10) was administered to patients with active mild-to-moderate Crohn's disease for 12 weeks. The agent's efficacy was assessed by evaluating clinical and endoscopic remission, healing of anal lesions, and blood levels of inflammatory markers. RESULTS: In the Theracurmin® group, a significant reduction in clinical disease activity was observed in week 12 relative to that in week 0 (p = 0.005). On intention-to-treat analysis, clinical remission rates were 35%, 40%, and 40% at weeks 4, 8, and 12, respectively, which were significantly higher than those in the placebo group (all 0%; p = 0.033, p = 0.020, and p = 0.020, respectively). Furthermore, reduction in endoscopic Crohn's disease severity (p = 0.032) was observed at week 12 in the Theracurmin® group. The endoscopic remission rates were 15% and 0% in the Theracurmin® and placebo groups, respectively. Significant healing of anal lesions (p = 0.017) was observed at week 8 in the Theracurmin® group. No serious adverse events were observed in either group throughout the study. CONCLUSIONS: Theracurmin® shows significant clinical and endoscopic efficacy together with a favorable safety profile in patients with active mild-to-moderate Crohn's disease. CLINICAL TRIAL UMIN REGISTRATION ID: UMIN000015770.

Assessment of Long-Term Efficacy and Safety of Adalimumab in Patients with Ulcerative Colitis: Results from a 6-Year Real-World Clinical Practice.

BACKGROUND: Although evidence for the short- to medium-term efficacy of adalimumab in ulcerative colitis (UC) patients is emerging, there are a limited number of reports on the long-term efficacy of adalimumab. This study was to understand baseline demographic features, which potentially could be risk factors for relapse or colectomy following induction of remission by adalimumab in UC patients. Additionally, factors affecting long-term outcomes were to be identified. METHODS: Twenty-one patients with UC who had been treated with adalimumab were reviewed retrospectively. Comparative analyses were undertaken by factoring steroid withdrawal versus non-withdrawal, long-term remission versus relapse following remission, and requiring surgical intervention for UC versus surgery-free. RESULTS: Adalimumab treatment was associated with steroid tapering in steroid-dependent cases in the long term. Of the 14 patients in whom clinical remission was achieved, the cumulative nonrelapse survival rate at 350 weeks was 43.8% and the cumulative nonoperative survival rate was 85.7%. Risk factors for surgery included intolerance to salicylates (p = 0.005) and past treatment with tacrolimus (p = 0.023). CONCLUSIONS: Adalimumab treatment was associated with long-term efficacy in patients with mild UC - patients achieved a high cumulative nonoperative survival rate over a long period of time, beyond 6 years.

A multicenter retrospective study aiming to identify patients who respond well to adsorptive granulomonocytapheresis in moderately to severely active ulcerative colitis.

OBJECTIVES: Adsorptive granulomonocytapheresis (GMA) with the Adacolumn has been introduced as a non-pharmacologic treatment for ulcerative colitis (UC). However, a subset of patients who might respond well to GMA needs to be targeted. This study was conducted at three IBD centers to determine factors affecting the efficacy of GMA in patients with moderately-to-severely active UC. METHODS: From January 2008 to December 2017, a total of 894 active episodes (first attack or relapse) in 593 patients were treated with GMA. Clinical remission was defined as normal stool frequency and no rectal bleeding. Multiple clinical and laboratory parameters at entry were considered for efficacy assessment. RESULTS: Clinical remission was achieved during 422 (47%) of the 894 treatment cases. In the multivariate analysis, predictors for favorable response to GMA were age ≤60 years, UC duration <1 year, Mayo endoscopic subscore 2 (vs. 3), steroid naïve UC, and biologic naïve UC. Clinical remission rate was 70% in patients with four of the five factors, 52% in patients with three factors, 46% in patients with two factors, 39% in patients with one factor, and 18% in patients with none of these factors. Overall, the clinical remission rate was significantly higher in patients with a greater number of the five predictors (P < 0.0001). CONCLUSIONS: GMA appeared to be effective in steroid naïve and biologic naïve patients with short duration of UC. Elderly patients (>60 years) and those with severe endoscopic activity did not respond well to GMA. Additional, well designed, prospective, controlled trials should strengthen our findings.

Adsorptive Depletion of Myeloid Lineage Leucocytes as Remission Induction Therapy in Patients with Ulcerative Colitis after Failure of First-Line Medications: Results from a Three-Year Real World, Clinical Practice.

BACKGROUND/AIMS: In patients with active ulcerative colitis (UC), pharmacologics, although initially effective in most patients, are associated with refractoriness, loss of response or unfavourable side effects as additional morbidity factors. Depletion of myeloid lineage leucocytes like the CD14(+)CD16(+) monocyte phenotype, which is a major source of tumour necrosis factor-α, by granulocyte/monocyte apheresis (GMA) if effective, is also known to be free from side effects. METHODS: In clinical practice setting, 77 consecutive patients with moderate to severe UC, who failed to respond to first-line medications received GMA with the Adacolumn as remission induction therapy. Patients who achieved remission were followed for 3 years. RESULTS: Among the 77 patients, 46.8% were corticosteroids-naïve, 26% corticosteroid-dependent and 27.3% corticosteroid-refractory. The overall clinical remission rate was 79.2%, and the overall mucosal healing (MH) rate according to the Mayo endoscopic subscore ≤1 was 58.5%. MH rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 70.8, 56.3, and 38.5%, respectively. The 3-year sustained clinical remission rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 83.3, 68.8, and 23.1%, respectively. CONCLUSION: Corticosteroid-naïve patients appeared to benefit the most from the Adacolumn GMA, and attain a favourable long-term clinical course. Accordingly, GMA should be a first-line therapy in this clinical setting.