Objectives and Study

We previously reported the effectiveness of vedolizumab to induce remission in children with Crohn’s disease (CD) and ulcerative colitis (UC) enrolled to the VEDOKIDS multicenter study. Here, we aimed to explore the effectiveness and safety of vedolizumab to maintain remission through week 30.

Methods

Children with CD/UC commenced on vedolizumab were prospective followed. The primary outcome was steroid- and exclusive enteral nutrition-free remission (SFR) at 30 weeks. Response was defined as ≥20 points change in PUCAI or >20 in wPCDAI and clinical remission as PUCAI<10 or wPCDAI<12.5.

Results

142 children were enrolled (65 [46%] CD, 77 [54%] UC). At week 30, all outcomes were higher in UC, but without statistical significance (Figure). Response to induction therapy predicted week-30 remission: of responders, 19 (59%) with CD and 31 (60%) with UC achieved SFR at week 30, compared to 3 (12%; p=0.004) and 5 (29%; p=0.03), in non-responders. In multivariable model, initial response was highly associated with week-30 SFR, in both CD (OR 11.2 [95%CI 2.3-73]) and UC (OR 4.8 [95%CI 1.4-19]). Of the 22 (18%) patients who were responders but not remitters at week 14, four eventually achieved SFR at week 30 (1/10 [10%] in CD and 3/12 [25%] in UC).

Adverse events (AEs) were possibly/definitely related to vedolizumab in 23 (16%) children, 11 of whom (31%) moderate and the others mild. No cases of progressive multifocal leukoencephalopathy or deaths were reported, while one case of Hodgkin's lymphoma (vedolizumab was resumed after completing the chemotherapy). Four children (1.4%) discontinued treatment due to AEs.

Conclusions

In this prospective multicenter study, vedolizumab was effective for maintaining remission in children with CD (34% SFR) and more so in UC (47%). Unlike the common notion, children with CD not achieving complete remission by week 14 have a low likelihood of entering remission thereafter.

Objectives and Study

Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD). However, they have often been limited by detection biases, (especially during the first year of follow-up), misclassification, and small sample size; and rarely reflect modern-day management of IBD.

Methods

Binational register-based cohort study (Sweden and Denmark) during 1969-2019. We compared 164,716 patients with IBD (of which 15,840 were diagnosed during childhood) to 1,639,027 matched general population reference individuals duringa a median follow-up of more than 10 years. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up.

Results

During 1969-2019, 258 patients with Crohn’s Disease (CD), 479 patients with ulcerative colitis (UC)(and 27 patients with childhood-onset IBD), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35(CD) and 34(UC)/100,000 person-years [PY] in IBD patients, compared to 28 and 33/100,000 PY in their matched reference individuals.

While both CD (HR=1.32; 95%CI=1.16-1.50) and UC (HR=1.09; 95%CI=1.00-1.20) were associated with an increase in lymphoma in the entire study population (all age groups), the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95%CI=0.02 to 0.13])). Childhood-onset CD was associated with lymphoma (HR=2.51; 95%CI=1.44-4.37), especially non-Hodgkin lymphoma (HR=3.53; 95%CI=1.75-7.13), whereas childhood-onset UC was not associated with lymphoma (HR=1.05; 95%CI=0.51-2.19).

Most CD phenotypes were associated with lymphoma, especially with non-Hodgkin Lymphoma (NHL), and HRs increased the last two decades. Since the year 2000, increased HRs were noted especially for aggressive B-cell NHL in CD and UC patients, and for T-cell NHL in CD patients. For UC, only extensive colitis or primary sclerosing cholangitis were associated with lymphoma risk.

Conclusions

During the past 20 years, HRs for lymphomas have increased in CD, but not in UC, and are driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.

Objectives and Study

Tofacitinib, a Janus kinase (JAK) inhibitor, has recently been approved for treatment of moderate to severe active ulcerative colitis (UC) in adults. Data on efficacy and safety in pediatrics are limited. In this multicenter study from the Paediatric IBD Porto group of ESPGHAN, we describe the short-term effectiveness and safety of tofacitinib in an international pediatric IBD cohort.

Methods

Retrospective review of children (2-18 years) diagnosed with UC treated with tofacitinib from 15 pediatric centers internationally. Primary outcome was corticosteroid-free clinical remission (PUCAI<10) at week 8, with secondary outcomes including clinical response (≥20 point decrease in PUCAI), colectomy rate and safety. Primary outcome was calculated utilizing non-response imputation (NRI), whereby drug cessation for any reason was considered treatment failure.

Results

78 patients (43 (55%) female, mean age at diagnosis 12.5 (±2.7) years, median disease duration 20 months (IQR 10.3-38.8)), all with previous biologic failure, including 20/78 (26%) with previous failure of three biologic classes.

15/78 (19%) patients achieved corticosteroid-free clinical remission at week 8 with a further 18/78 (23%) demonstrating clinical response. 9/78 (12%) underwent colectomy by week 8, and 21/78 (27%) by week 24. Twelve adverse events were reported including five infective (three of which deemed possibly related to treatment – zoster, HSV-2 cheilitis and septic arthritis), one case of pancreatitis, and abnormal blood test results in 5 children (anemia, lymphopenia, elevated hepatic transaminases and hypercholesterolemia).

Conclusions

In this largest real-life cohort of tofacitinib in pediatric UC to date, tofacitinib seemed effective in at least 19% of highly refractory patients by week 8. Adverse reactions and safety were largely consistent with adult data.