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    Home > Active Ingredient News > Digestive System Information > [Good news] Adalimumab of the original research has received new indications, and the treatment of Crohn's disease in children ushered in a new dawn!

    [Good news] Adalimumab of the original research has received new indications, and the treatment of Crohn's disease in children ushered in a new dawn!

    • Last Update: 2021-05-09
    • Source: Internet
    • Author: User
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    It is only for medical professionals to read for reference.
    Children's Crohn's disease has complex manifestations and rapid progress, but the clinically available therapeutic drugs are limited.
    Previously, the only biological preparation was intravenous infliximab.

    Today, the original adalimumab injected subcutaneously has significant efficacy, safety and convenience, and brings new treatment options for children with Crohn's disease.

    Crohn’s disease (CD) is a more common chronic inflammatory bowel disease.
    The peak period of the disease is the adolescent period.
    Epidemiological data shows that 25% to 30% of patients develop before the age of 20, and 4% Children with CD onset before the age of 5 years [1].

    Children's CD manifestations are complex.
    In addition to intestinal symptoms such as abdominal pain, diarrhea, fistula, and perianal disease, it may also be combined with other extraintestinal manifestations such as skin erythema nodosa, arthritis, growth disorders, etc.

    Compared with adult CD, childhood CD has the characteristics of extensive involvement and rapid progress [2], and the diagnosis and treatment of the disease has certain difficulties.

     Today AbbVie announced that the National Medical Products Administration (NMPA) of China has approved its product Humira (formerly adalimumab) for children's CD.
    This is also the third child that the original adalimumab has been approved in China.
    The indications have brought new hope for the majority of children with autoimmune diseases.

     New trend! Biological preparations have become the first-line recommendation of authoritative guides at home and abroad.
    Since the beginning of the new century, biological preparations have been widely used in the field of inflammatory bowel disease.
    Related clinical studies have sprung up and achieved gratifying results.

    Adalimumab is the world’s first fully human anti-tumor necrosis factor (TNF) monoclonal antibody.
    The original research adalimumab has been approved for 17 indications worldwide, including children’s CD, children’s psoriasis, and multiple Juvenile idiopathic arthritis, enthesitis-related arthritis and other 7 childhood indications, the effectiveness and safety of a variety of childhood autoimmune diseases have been fully confirmed by a number of clinical studies and strong long-term practical experience stand by.

     Based on sufficient evidence-based evidence, a number of authoritative guidelines at home and abroad recommend Adalimumab for moderate to severe childhood CD patients who are ineffective or intolerant to traditional drug therapy, and conditionally recommend it for the first-line treatment of some children with CD patients (Table 1) [3-5].

     Table 1 Authoritative guidelines at home and abroad recommend Adalimumab for the first-line treatment of some children with CD [3-5] Note: ECCO, European Crohn’s Disease and Colitis Organization; ESPGHAN, Hepatology and Nutrition Association; CAG, Canadian Stomach The Enterology Association speaks about the evidence! The results of the study provide strong support for the approval of adalimumab ■ Significant efficacy IMAgINE 1 trial is the first randomized double-blind trial to evaluate the efficacy of adalimumab in the treatment of children with CD.
    The study included 192 patients with moderate to severe CD between the ages of 6 and 17 In children, 188 patients who achieved clinical remission after induction therapy were randomly divided into two different dose groups for double-blind trials.

    Studies have shown that the standard dose group (ie 40 mg for those with a body weight ≥ 40 kg and 20 mg for those with a weight less than 40 kg) received adalimumab for 26 weeks, the PCDAI clinical response rate (compared to The baseline PCDAI decrease ≥15) was 59.
    1%, and at 52 weeks, the clinical response rate was 41.
    9% (Figure 1).

     Figure 1 Clinical response rate of standard dose group At 26 weeks, the clinical remission rate (PCDAI score ≤10) of standard dose group was 38.
    7%.

    The clinical remission rate at 52 weeks was 33.
    3% (Figure 2) [6].

    The research results confirmed that adalimumab can effectively improve the clinical symptoms of children with CD, and improve clinical remission and clinical response.

     Figure 2 Clinical remission rate in the standard dose group.
    In addition, real data studies also show that 91.
    9% of patients can achieve clinical remission after adalimumab treatment for 1 year (Figure 3) [7], confirming that adalimumab is in the real world It also has outstanding performance in clinical practice.

     Figure 3 The clinical remission rate of adalimumab in the treatment of children with CD in a real-world study ■ Durable and stable IMAgINE 2 trial A 240-week follow-up observation was conducted for children with CD who achieved remission or response in the IMAgINE 1 trial.

    The results showed that 93.
    5% of the children who had achieved a treatment response at the time of entry into the study maintained a response during the 240-week treatment period.
    Among the children who had achieved clinical remission at the time of entry into the study, 80.
    4% of the children could maintain clinical remission ( Figure 4, Figure 5), fully confirmed that adalimumab has a long-term and stable effect on children with CD [8].

     Figure 4 IMAgINE 2 study children's treatment response rate Figure 5 IMAgINE 2 study children's clinical remission rate ■ promote fistula closure The IMAgINE 1 trial subgroup analysis, a total of 36 children with fistula at baseline, 50 at 12 weeks of treatment % Of patients achieved fistula closure, and 42.
    3% of patients achieved fistula closure at 52 weeks.

    In addition, 90.
    9% of patients who achieved fistula closure at 12 weeks were still able to maintain fistula closure during the 292-week follow-up treatment period, further confirming that long-term treatment with adalimumab can effectively promote fistula closure (Figure 6) [9].

     Figure 6 Adalimumab treatment of fistula closure response rate in children with CD ■ Maintaining normal growth in children is a common symptom of children with CD.

    At baseline in the IMAgINE 1 trial, the average z-score of the standard dose group was -0.
    37.
    After 26 weeks of treatment, the average z-score improved to 1.
    38.
    At 52 weeks of treatment, the average z-score rose to 2.
    07, which was a significant improvement from baseline (Figure 7) It is confirmed that adalimumab can effectively promote the normalization of children's growth rate [6].

     Figure 7 Changes in z-scores of children with growth disorders at baseline at 52 weeks of treatment.
    The real world also shows that when children with CD receive adalimumab treatment for 52 weeks, the average z-scores are significantly improved.
    Among them, severe growth disorders (baseline z-scores) The average z-score of patients with <-2.
    5) rose to 0.
    3 after treatment, further confirming that adalimumab can help promote the normal growth of children with CD (Figure 8) [7].

     Figure 8 The effect of adalimumab on the growth rate of children with CD in the real world.
    Among the children who entered the IMAgINE 2 trial, 58 children had growth disorders at the baseline of the IMAgINE 1 study, with an average z-score of -2.
    81, the results showed After receiving adalimumab treatment, at 48 weeks of the IMAgINE 2 study, the average z-score rose to 0.
    85.
    The long-term results showed that the normalized growth rate of children could be maintained up to 192 weeks [8].

    ■ Safe tolerance Because children are in the growth and development period, many organs and systems are not yet perfect, drug excretion is slow, and adverse reactions such as drug poisoning and infection are prone to occur.
    Therefore, doctors pay more attention to the safety of children's medication.

    Studies have shown that adalimumab has good long-term safety in the treatment of children with CD [8].

    In addition, Adalimumab is a biological preparation for subcutaneous injection.
    The common adverse reactions are injection site reactions (such as redness, bleeding, pain, etc.
    ), and most of them are mild.
    Generally speaking, there is no need to stop medication due to injection site reactions.

     In summary, the incidence of CD in children has risen sharply in the past 10 years, and the demand for treatment has continued to rise.

    At present, many authoritative guidelines at home and abroad recommend Adalimumab for moderate to severe childhood CD patients who are ineffective or intolerant to traditional drug therapy, and conditionally recommend it for the first-line treatment of some children's CD.

    Clinical studies have shown that adalimumab treatment of children with CD can significantly improve the clinical symptoms of patients, promote fistula closure, maintain normal growth of children, and have long-lasting and stable curative effects and good overall safety.

    The original research adalimumab was approved for new indications in China, bringing new dawn to patients with moderate to severe childhood CD.

    Medication Tips When the original adalimumab is clinically used in the treatment of children with CD, it is recommended to administer according to body weight.

    For patients less than 40kg, the induction dose is 80mg initially, 40mg is given two weeks later, and 20mg every two weeks thereafter; for patients ≥40kg, 160mg should be given on the first day, and 80mg should be given two weeks later and maintained thereafter 40mg every two weeks (Figure 9).

    The time to determine primary non-response should not be earlier than 12 weeks after treatment.

     Figure 9 The original research on the usage and dosage of adalimumab in children with CD.
    References: [1] Qian Jiaming, Yang Hong.
    Historical retrospect of research on inflammatory bowel disease in China, current status and prospects[J].
    Chinese Journal of Practical Internal Medicine, 2015,35(09 ):727-730.
    [2] Rubio CA, Orrego A, Nesi G, et al.
    Frequency of epithelioid granulomas in colonoscopic biopsy specimens from paediatric and adult patients with Crohn's colitis.
    [J].
    Journal of Clinical Pathology, 2007, 60 (11):1268.
    [3] van Rheenen PF, Aloi M, Assa A,et al.
    The Medical Management of Paediatric Crohn's Disease: an ECCO-ESPGHAN Guideline Update.
    J Crohns Colitis.
    2020 Oct 7:jjaa161.
    [4] Mack DR, Benchimol EI, Critch J, et al.
    Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn's Disease.
    Gastroenterology.
    2019;1-29.
    [5] Gastroenterology Group, Pediatrics Branch of Chinese Medical Association, Clinical Nutrition Group of Pediatrics Branch of Chinese Medical Association.
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    Chinese Journal of Pediatrics,2019,57 (7): 501-507.
    [6] Hyams JS, Griffiths A, Markowitz J, et al.
    Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children.
    Gastroenterology.
    2012 Aug;143(2):365-74.
    e2.
    [7] Víctor Manuel Navas-López, Pujol-Muncunill G, Llerena E, et al.
    [A real-world study focused on the effectiveness and safety of adalimumab as first-line anti-TNF treatment for pediatric Crohn's disease].
    [J].
    Anales de Pediatría (English Edition), 2017.
    [8] Faubion WA, Dubinsky M , Ruemmele FM,et al.
    Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease.
    Inflamm Bowel Dis.
    2017 Mar;23(3):453-460.
    [9] Ruemmele FM, Rosh J, Faubion WA, et al.
    Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2.
    J Crohns Colitis.
    2018 Nov 9;12(10):1249-1254.
    Statement:statement:statement:143(2):365-74.
    e2.
    [7] Víctor Manuel Navas-López, Pujol-Muncunill G, Llerena E, et al.
    [A real-world study focused on the effectiveness and safety of adalimumab as first-line anti -TNF treatment for pediatric Crohn's disease].
    [J].
    Anales de Pediatría (English Edition), 2017.
    [8] Faubion WA, Dubinsky M, Ruemmele FM,et al.
    Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease.
    Inflamm Bowel Dis.
    2017 Mar;23(3):453-460.
    [9] Ruemmele FM, Rosh J, Faubion WA,et al.
    Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2.
    J Crohns Colitis.
    2018 Nov 9;12(10):1249-1254.
    Statement:143(2):365-74.
    e2.
    [7] Víctor Manuel Navas-López, Pujol-Muncunill G, Llerena E, et al.
    [A real-world study focused on the effectiveness and safety of adalimumab as first-line anti -TNF treatment for pediatric Crohn's disease].
    [J].
    Anales de Pediatría (English Edition), 2017.
    [8] Faubion WA, Dubinsky M, Ruemmele FM,et al.
    Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease.
    Inflamm Bowel Dis.
    2017 Mar;23(3):453-460.
    [9] Ruemmele FM, Rosh J, Faubion WA,et al.
    Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2.
    J Crohns Colitis.
    2018 Nov 9;12(10):1249-1254.
    Statement:[A real-world study focused on the effectiveness and safety of adalimumab as first-line anti-TNF treatment for pediatric Crohn's disease].
    [J].
    Anales de Pediatría (English Edition), 2017.
    [8] Faubion WA, Dubinsky M , Ruemmele FM,et al.
    Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease.
    Inflamm Bowel Dis.
    2017 Mar;23(3):453-460.
    [9] Ruemmele FM, Rosh J, Faubion WA, et al.
    Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2.
    J Crohns Colitis.
    2018 Nov 9;12(10):1249-1254.
    Statement:[A real-world study focused on the effectiveness and safety of adalimumab as first-line anti-TNF treatment for pediatric Crohn's disease].
    [J].
    Anales de Pediatría (English Edition), 2017.
    [8] Faubion WA, Dubinsky M , Ruemmele FM,et al.
    Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease.
    Inflamm Bowel Dis.
    2017 Mar;23(3):453-460.
    [9] Ruemmele FM, Rosh J, Faubion WA, et al.
    Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2.
    J Crohns Colitis.
    2018 Nov 9;12(10):1249-1254.
    Statement:Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease.
    Inflamm Bowel Dis.
    2017 Mar;23(3):453-460.
    [9] Ruemmele FM, Rosh J, Faubion WA,et al.
    Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2.
    J Crohns Colitis.
    2018 Nov 9;12(10):1249-1254.
    Statement:Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease.
    Inflamm Bowel Dis.
    2017 Mar;23(3):453-460.
    [9] Ruemmele FM, Rosh J, Faubion WA,et al.
    Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2.
    J Crohns Colitis.
    2018 Nov 9;12(10):1249-1254.
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