AbbVie's HUMIRA® Approved in China for Polyarticular Juvenile Idiopathic Arthritis

Shanghai, December 20, 2019 /PRNewswire/ -- Recently, AbbVie, a top-10 global biopharmaceutical company, announced that the National Medical Products Administration (NMPA) of China has approved Humira^®(Adalimumab Injection) is indicated for the treatment of polyarticular juvenile idiopathic arthritis (pJIA). This is Humira.^®The fourth indication approved in China also marks Humira's^®Humira Enters a New Therapeutic Field in China—Pediatrics, Following Rheumatology and Dermatology^®It is the first fully human (TNFi) monoclonal antibody approved in China for the treatment of polyarticular juvenile idiopathic arthritis.

This indication has received approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration to waive Chinese clinical trials, with its approval based on multiple assessments of Humira.^®Pivotal Study on the Efficacy and Safety of Treatment for pJIA.^{[4]、 [5] 、[6]}

“Juvenile idiopathic arthritis is the most common rheumatic disease in childhood, often persisting from childhood into adulthood. It is characterized by a prolonged course, frequent relapses, and a high rate of disability. Affected children experience limitations in daily activities due to joint stiffness and swelling, preventing them from running, jumping, or playing with peers normally. In addition to joint inflammation and deformity, systemic symptoms and visceral involvement are common, including rash, uveitis, hepatosplenomegaly, lymphadenopathy, pleuritis, pericarditis, and interstitial pneumonia. Currently, conventional chemical drugs can only alleviate the symptoms of polyarticular juvenile idiopathic arthritis (pJIA), have significant side effects, and fail to control disease progression in all patients, highlighting an urgent need for innovative therapeutic approaches and biologic targeted agents,” stated Professor Li Caifeng, Director of the Department of Rheumatology and Immunology at Beijing Children’s Hospital, Capital Medical University. “Humira^®The approval of adalimumab injection provides a valuable treatment option for pediatric patients in China and their families. HUMIRA® is administered via subcutaneous injection once every two weeks, supported by multiple global clinical studies^{[4]、[5]、[6]、[7]}Display, Humira^®As a fully human monoclonal antibody, it takes effect within two weeks with stable efficacy, good safety profile, and low incidence of injection reactions and adverse reactions, demonstrating excellent tolerability in pediatric patients. As the only biologic agent currently approved in mainland China for the treatment of polyarticular juvenile idiopathic arthritis (pJIA), we look forward to Humira^®Can help children with pJIA control disease progression and reclaim the joyful moments of childhood and adolescence.”

Oussama Lahlou, General Manager of AbbVie China, stated, “In China, the treatment needs of patients with polyarticular juvenile idiopathic arthritis (pJIA) and their families remain unmet. Humira^®Approval of the pJIA indication can provide them with a new treatment option. Currently, Humira^®Humira has received global approval for 17 immune-mediated disease indications, benefiting over one million patients. Amid the current landscape in China, characterized by the implementation of policies accelerating the review and approval of new drugs and the continuous advancement of adjustments to the National Reimbursement Drug List, we also look forward to Humira^®"to serve more Chinese patients across a broader range of disease areas."

As a pediatric medication with significant clinical advantages, this time Humira^®(Adalimumab Injection) The application for the pJIA indication was granted eligibility for waiver of China registration clinical trials and priority review and approval by the Center for Drug Evaluation (CDE) of the National Medical Products Administration.^[8]。

2008, Humira^®Approved in the United States for the treatment of patients aged 4 years and older with polyarticular juvenile idiopathic arthritis (pJIA); in 2014, the age range for this indication was expanded to include patients aged 2 years and older with pJIA, and Orphan Drug Designation was granted for the treatment of pJIA in patients aged 2–17 years. In the European Union, Humira^®It was approved in 2008 for the treatment of patients aged 13–17 years with polyarticular juvenile idiopathic arthritis (pJIA). In 2011, its indication for pJIA was expanded to include patients aged 4–17 years, and in 2013, the age range for the pJIA indication was further expanded to include patients aged 2–17 years.

Humira^®Key Clinical Studies for the Treatment of Polyarticular Juvenile Idiopathic Arthritis

Adalimumab with or without Methotrexate for the Treatment of Juvenile Rheumatoid Arthritis^[4]

This is a randomized, double-blind, stratified, placebo-controlled, multicenter, dosing-withdrawal study comprising a 16-week open-label lead-in period, a 32-week double-blind withdrawal period, and an open-label extension period.

Pediatric patients aged 4 to 17 years with active rheumatoid arthritis who had previously received nonsteroidal anti-inflammatory drug (NSAID) therapy were stratified based on methotrexate use, at a dose of 24 mg/m² by body surface area²Adalimumab (maximum dose of 40 mg) was administered via subcutaneous injection every other week for 16 weeks. At Week 16, patients who achieved a 30% improvement according to the American College of Rheumatology Pediatric Criteria (ACR Pedi 30) were randomized in a double-blind manner to receive either adalimumab or placebo every other week for up to Week 32.

At Week 16, 74% of patients not receiving methotrexate (64 out of 86) and 94% of patients receiving methotrexate (80 out of 85) met the ACR-Pedi 30 response criteria and were eligible for double-blind treatment. Among patients not receiving methotrexate, disease flare (primary outcome) occurred in 43% of those treated with adalimumab and 71% of those treated with placebo (P=0.03). Among patients receiving methotrexate, disease flare occurred in 37% of those treated with adalimumab and 65% of those treated with placebo (P=0.02). At Week 48, among patients receiving methotrexate, the percentages of patients treated with adalimumab achieving ACR-Pedi 30, 50, 70, or 90 responses were significantly higher than those treated with placebo; among patients not receiving methotrexate, the difference between patients treated with adalimumab and those treated with placebo was not significant. The response rates remained stable after 104 weeks of treatment. During the study, there were no reports of death, malignancy, opportunistic infections, tuberculosis, demyelinating diseases, or lupus-like syndrome.

Adalimumab TreatmentSafety, Efficacy, and Pharmacokinetics of Polyarticular Juvenile Idiopathic Arthritis in Children Aged 2–4 Years^[5]

The objective of this study was to evaluate the safety of adalimumab in the treatment of moderate-to-severe active polyarticular juvenile idiopathic arthritis (pJIA) in children aged 2–4 years or ≥4 years of age with body weight <15 kg, as well as to assess its clinical efficacy and pharmacokinetics. This was an international, multicenter, open-label, Phase 3b study enrolling 32 patients with active JIA. These patients received adalimumab at a dose of 24 mg/m²²(Maximum dose = 20 mg/dose) administered once every other week for up to 120 weeks, with or without methotrexate. Adverse events (AEs) were summarized for completed visits. Efficacy endpoints included the American College of Rheumatology Pediatric Criteria (PedACR) 30/50/70/90 response and JIA core variables. Adalimumab serum trough concentrations were measured in a subset of patients. Of these patients, 88% were female. The mean baseline age, weight, and duration of JIA were 3 years, 13 kg, and 12 months, respectively; 39% of patients had elevated C-reactive protein. AE incidence rates included any AE (29/32, 91%), serious AE (5/32, 16%), infectious AE (25/32, 78%), and serious infection (3/32, 9%). No deaths, malignancies, or opportunistic infections were reported. Growth was not adversely affected. At week 96, 92% of patients achieved PedACR30, and 77% achieved PedACR70. Improvements in JIA core variables were observed. The mean steady-state serum adalimumab trough concentrations at weeks 12 and 24 were 7–8 μg/mL. Aged 2–4 years or>=Adalimumab was well tolerated in JIA patients aged 4 years with body weight <15 kg. The efficacy and pharmacokinetics of adalimumab were similar to those in older JIA patients.

In summary:

Efficacy, Pharmacokinetics, and Safety of Adalimumab in Pediatric Patients with Juvenile Idiopathic Arthritis in Japan^[6]

This study aimed to evaluate the efficacy, pharmacokinetics, and safety of adalimumab in the treatment of Japanese patients with polyarticular juvenile idiopathic arthritis (pJIA). This single-arm, open-label, multicenter study of adalimumab enrolled patients aged 4 to 17 years. Patients weighing <30 kg received a dose of 20 mg every other week (eow), weight>=30kg patient dose is 40mg eow. Methotrexate (MTX) combination therapy is allowed (weekly<=10 mg/m²). The primary efficacy outcome was the percentage of patients achieving American College of Rheumatology Pediatric 30 (ACR Pedi 30) response at Week 16. JIA core variables, serum adalimumab concentrations, and anti-adalimumab antibodies (AAA) were analyzed. Adverse events (AEs) were monitored in patients. A total of 25 patients were enrolled (20 receiving concomitant methotrexate [MTX] at baseline and 5 not receiving concomitant MTX): 24 completed 16 weeks of treatment, and 22 completed 60 weeks of treatment. At Week 16, 90% of patients receiving concomitant MTX and 100% of those not receiving concomitant MTX achieved ACR Pedi 30; at Week 60, the response rates were maintained in 94% and 80% of patients, respectively. All JIA core variables improved over time. Six patients tested positive for AAA (two each at Weeks 8, 16, and 60), some of which were transient. All six AAA-positive patients achieved ACR Pedi 30 at Week 16, and four of them maintained ACR Pedi 30 at Week 60. Nine serious AEs occurred in six patients (all receiving concomitant MTX): JIA flare, fever, arthralgia, pneumonia, hepatitis B virus infection, pharyngitis, dehydration, sore throat, and pneumonia. The safety profile of adalimumab in Japanese patients with polyarticular juvenile idiopathic arthritis was similar to that reported in Western studies, with no new safety signals identified. Adalimumab was safe and effective in reducing disease activity over a period of up to 60 weeks.

Safety and Efficacy of Adalimumab in the Disease Course of Polyarticular Juvenile Idiopathic Arthritis:STRIVE Registry: 7-Year Mid-Term Results^[7]

The objective of this study was to evaluate the safety and efficacy of adalimumab (ADA) in polyarticular-course juvenile idiopathic arthritis (pcJIA) within the STRIVE registry (NCT00783510).

Based on treatment with methotrexate (MTX) monotherapy or adalimumab (ADA) with or without MTX (ADA±MTX), the STRIVE study enrolled patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) into two cohorts. The registry cohort analyzed adverse events (AEs) per 100 patient-years (PY) of observation. Patients who entered the registry within 4 weeks of initiating MTX or ADA±MTX (defined as new users) had changes in disease activity assessed using the 27-joint Juvenile Arthritis Disease Activity Score based on C-reactive protein (JADAS27-CRP).

At the 7-year cutoff date (June 1, 2016), data were available for 838 patients (MTX group, N=301; ADA±MTX group, N=537). The most common adverse events (AEs) in the MTX group were nausea (10.3%), sinusitis (4.7%), and vomiting (4.3%); the most common AEs in the ADA±MTX group were arthritis (3.9%), upper respiratory tract infection (3.5%), sinusitis, tonsillitis, and injection site pain (each 3.0%). The rate of serious infections was 1.5 events per 100 patient-years (PY) in the MTX group and 2.0 events per 100 PY in the ADA±MTX group. The incidence of AEs and serious AEs was similar among patients receiving ADA with or without MTX. No deaths, active tuberculosis cases, or malignancies were reported. Compared with new users in the MTX group during the first year of STRIVE, new users in the ADA±MTX group showed a trend toward lower mean JADAS27-CRP scores.

The 7-year interim results from the STRIVE registry support that ADA ± MTX is well tolerated in most children. The median (interquartile range) duration of ADA exposure in the registry was 2.47 (1.0–3.6) years, with 42% of patients continuing ADA treatment at the 7-year cutoff.

GuanHumira^®(Adalimumab Injection)

Humira^®(Adalimumab Injection) is the world's first fully human anti-tumor necrosis factor monoclonal antibody approved for marketing. Excessive inflammation in various immune-mediated diseases in humans is associated with tumor necrosis factor-alpha (TNF-α), Humira^®(Adalimumab Injection) can selectively bind to TNF-α molecules, preventing their attachment to healthy cells, thereby reducing damage caused by excessive TNF-α. Based on this principle, Humira^®(Adalimumab Injection) can be used to treat various immune-mediated diseases.

Humira, since its market launch in 2003,^®(Adalimumab Injection) has helped numerous patients with immune diseases worldwide. Currently, Humira^®(Adalimumab Injection) has received approval for 17 indications globally. At least one indication has been approved in more than 100 countries and regions worldwide. Currently, over 1 million patients globally are using Humira.^®(Adalimumab Injection) treatment. Globally, Humira^®(Adalimumab Injection) boasts over 20 years of research data, more than 100 clinical studies, and coverage of over 33,000 patients.

Humira^®(Adalimumab Injection) is available in two administration forms: pre-filled syringes and pre-filled injection pens (“Humira Pen”). The pre-filled injection pen offers convenient use, allowing patients to self-administer the injection under the guidance of qualified healthcare professionals.

In China, Humira^®(Adalimumab Injection) was launched in 2010 and has currently been approved for four indications: rheumatoid arthritis (approved in 2010), ankylosing spondylitis (approved in 2013), moderate-to-severe plaque psoriasis (approved in 2017), and polyarticular juvenile idiopathic arthritis (approved in 2019). In 2018, the China National Medical Products Administration (NMPA) approved Humira^®(Adalimumab Injection) The indicated population for adult psoriasis has been changed to “adult patients with moderate-to-severe chronic plaque psoriasis who require systemic therapy,” shifting its status from a second-line to a first-line systemic therapeutic agent in clinical practice. Meanwhile, the NMPA has also approved the revision for Humira^®(Adalimumab Injection) Add the results of clinical trials on psoriatic nails to the package insert in China.

Currently, Humira^®(Adalimumab Injection) has been included in the "National Reimbursement Drug List for Basic Medical Insurance, Work-Related Injury Insurance, and Maternity Insurance," with covered indications including rheumatoid arthritis, ankylosing spondylitis, and moderate-to-severe plaque psoriasis. In the future, Humira^®(Adalimumab Injection) is expected to continue expanding into new indications. Humira^®(Adalimumab Injection) Indications for the Treatment of Non-infectious Intermediate Uveitis, Posterior Uveitis, and Panuveitis^[9]It has been included in China’s second batch of the List of Overseas New Drugs Urgently Needed for Clinical Use.

About AbbVie

AbbVie is a research-based global biopharmaceutical company dedicated to developing and promoting industry-leading innovative therapies to address some of the world’s most complex and challenging health issues. Leveraging specialized expertise, dedicated employees, and a unique approach to innovation, AbbVie focuses on significantly advancing treatments in four core therapeutic areas: immunology, oncology, virology, and neuroscience. With employees in more than 75 countries worldwide, AbbVie is working collectively to make a lasting impact on people’s health.

AbbVie China’s headquarters is located in Shanghai, focusing on four key therapeutic areas: immunology, virology, nephrology, and anesthesiology, with plans to expand into oncology in the future. Please scan the QR code below to follow AbbVie China’s official WeChat account for more information.

[1]  Hashkes PJ, et al.  JAMA. 2005 Oct 5;294(13):1671-84

[2]  Flatø B, et. Clin Rheumatol. 1998;17(6):505-10.

[3]  Wallace CA . Arthritis Rheum. 1998 Mar;41(3):381-91.

[4]  Lovell DJ, et al. N Engl J Med. 2008 Aug 21;359(8):810-20.

[5]  Kingsbury DJ, et al. Clin Rheumatol. 2014;33(10):1433-41.

[6]  Imagawa T, et al. Clin Rheumatol. 2012 Dec;31(12):1713-213

[7]  Brunner HI , et al.  Arthritis Care Res (Hoboken). 2019 Aug 17. doi: 10.1002/acr.24044

[8] List of drugs included in the priority review by the Center for Drug Evaluation, National Medical Products Administration, sourced from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21

[9] This indication is currently under registration with the National Medical Products Administration of China, but marketing approval has not yet been obtained.