In the JournalsPerspective

Adalimumab well-tolerated by most children with polyarticular JIA

Adalimumab, with or without methotrexate, is well-tolerated over a period of at least 7 years among most children with polyarticular-course juvenile idiopathic arthritis, according to data published Arthritis Care & Research.

“Children with [polyarticular-course] JIA are often treated with synthetic or biologic disease-modifying antirheumatic drugs or combination of both. Methotrexate is the most commonly used synthetic DMARD,” Hermine I. Brunner, MD, MSc, MBA, FAAP, FACR, of Cincinnati Children’s Hospital, and colleagues wrote. “However, in at least 40% of patients with JIA, [methotrexate] therapy will not result in adequate disease control. Children with inadequate response or intolerance to [methotrexate] require treatment with biologic DMARDs, such as inhibitors of tumor necrosis factor or other pro-inflammatory pathways.”

To analyze the safety and effectiveness of adalimumab (Humira, AbbVie) among children with polyarticular-course JIA, Brunner and colleagues reported on 7-year interim results from the STRIVE registry, an on-going, 10-year multicenter, non-interventional, observational trial. The registry includes children with polyarticular-course JIA treated with either methotrexate alone or adalimumab, alone or in combination with methotrexate, from 92 centers in 16 countries. All eligible patients were aged 2 to 17 years at enrollment. According to the researchers, STRIVE is part of a post-marketing commitment from AbbVie to the FDA.

At the 7-year cut-off date, June 1, 2016, data from 838 patients were available. This group included 301 patients who received methotrexate alone, 160 treated with adalimumab alone and 377 who received both drugs. The researchers analyzed adverse events per 100 patient years of observation time in each registry arm. Participants who entered the registry within 4 weeks of starting methotrexate or either adalimumab arm were characterized as “new users,” and were assessed for changes in disease activity based on C-reactive protein–based 27-joint Juvenile Arthritis Disease Activity Score (JADAS27CRP).

According to the researchers, among participants who received methotrexate alone, 10.3% experienced nausea, 4.7% demonstrated sinusitis, 4.3% had vomiting. Among those treated with adalimumab, either alone or with methotrexate, 3.9% experienced arthritis, 3.5% demonstrated upper respiratory tract infection, and sinusitis, tonsillitis and injection site pain were each reported in 3%. The serious infection rate in the methotrexate-alone arm was 1.5 events per 100 patient-years, and 2 events per 100 patient-years in the adalimumab group.

In addition, adverse events and serious adverse event rates were similar among patients treated with adalimumab either alone or with methotrexate. The researchers reported no deaths or malignancies. Lastly, participants defined as new users in the adalimumab group demonstrated a trend of lower mean JADAS27CRP, compared with new users treated with methotrexate alone in the first year of the registry.

“The 7-year interim results in this ongoing post-marketing registry show that [adalimumab] continues to be well tolerated in these patients with active [polyarticular-course] JIA,” Brunner and colleagues wrote. “No new safety signals were observed, and the safety of [adalimumab] in this patient population was comparable to that observed in prior [polyarticular-course] JIA studies. The known safety profile of [adalimumab] remains unchanged.” – by Jason Laday

Disclosure: Brunner reports speaker honoraria and consulting fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Centocor, Genentech, Hoffman LaRoche, Novartis, Pfizer, Regeneron, Takeda and UCB, as well as speaking fees from Genentech Pharmaceuticals. Please see the full study for additional authors’ disclosures.

Adalimumab, with or without methotrexate, is well-tolerated over a period of at least 7 years among most children with polyarticular-course juvenile idiopathic arthritis, according to data published Arthritis Care & Research.

“Children with [polyarticular-course] JIA are often treated with synthetic or biologic disease-modifying antirheumatic drugs or combination of both. Methotrexate is the most commonly used synthetic DMARD,” Hermine I. Brunner, MD, MSc, MBA, FAAP, FACR, of Cincinnati Children’s Hospital, and colleagues wrote. “However, in at least 40% of patients with JIA, [methotrexate] therapy will not result in adequate disease control. Children with inadequate response or intolerance to [methotrexate] require treatment with biologic DMARDs, such as inhibitors of tumor necrosis factor or other pro-inflammatory pathways.”

To analyze the safety and effectiveness of adalimumab (Humira, AbbVie) among children with polyarticular-course JIA, Brunner and colleagues reported on 7-year interim results from the STRIVE registry, an on-going, 10-year multicenter, non-interventional, observational trial. The registry includes children with polyarticular-course JIA treated with either methotrexate alone or adalimumab, alone or in combination with methotrexate, from 92 centers in 16 countries. All eligible patients were aged 2 to 17 years at enrollment. According to the researchers, STRIVE is part of a post-marketing commitment from AbbVie to the FDA.

At the 7-year cut-off date, June 1, 2016, data from 838 patients were available. This group included 301 patients who received methotrexate alone, 160 treated with adalimumab alone and 377 who received both drugs. The researchers analyzed adverse events per 100 patient years of observation time in each registry arm. Participants who entered the registry within 4 weeks of starting methotrexate or either adalimumab arm were characterized as “new users,” and were assessed for changes in disease activity based on C-reactive protein–based 27-joint Juvenile Arthritis Disease Activity Score (JADAS27CRP).

According to the researchers, among participants who received methotrexate alone, 10.3% experienced nausea, 4.7% demonstrated sinusitis, 4.3% had vomiting. Among those treated with adalimumab, either alone or with methotrexate, 3.9% experienced arthritis, 3.5% demonstrated upper respiratory tract infection, and sinusitis, tonsillitis and injection site pain were each reported in 3%. The serious infection rate in the methotrexate-alone arm was 1.5 events per 100 patient-years, and 2 events per 100 patient-years in the adalimumab group.

In addition, adverse events and serious adverse event rates were similar among patients treated with adalimumab either alone or with methotrexate. The researchers reported no deaths or malignancies. Lastly, participants defined as new users in the adalimumab group demonstrated a trend of lower mean JADAS27CRP, compared with new users treated with methotrexate alone in the first year of the registry.

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“The 7-year interim results in this ongoing post-marketing registry show that [adalimumab] continues to be well tolerated in these patients with active [polyarticular-course] JIA,” Brunner and colleagues wrote. “No new safety signals were observed, and the safety of [adalimumab] in this patient population was comparable to that observed in prior [polyarticular-course] JIA studies. The known safety profile of [adalimumab] remains unchanged.” – by Jason Laday

Disclosure: Brunner reports speaker honoraria and consulting fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Centocor, Genentech, Hoffman LaRoche, Novartis, Pfizer, Regeneron, Takeda and UCB, as well as speaking fees from Genentech Pharmaceuticals. Please see the full study for additional authors’ disclosures.

    Perspective
    David A. McLain

    David A. McLain

    With the use of the international STRIVE registry, patients aged 2 to 17 years old with moderately-to-severely active JIA (5 joints with arthritis) were enrolled in this phase IV routine clinical care post-marketing surveillance study. Patients were enrolled who were being treated with methotrexate alone or adalimumab with or without methotrexate, and had to commence both adalimumab and methotrexate within 24 months of entry into the study.

    This study showed that adalimumab was well-tolerated in both arms of the study. No deaths, malignancies, active tuberculosis, demyelinating disorders or congestive heart failure were reported with the adalimumab arm. This should provide comfort to parents (and older juveniles) who, for fear of side effects, sometimes choose no treatment for their child instead of a drug that has been shown to be effective and safe. The methotrexate alone group had a 33% discontinuation rate due to lack of efficacy vs. a 4% rate in the adalimumab with or without methotrexate group.

    • David A. McLain, MD, FACP, FACR
    • Executive director, Alabama Society for the Rheumatic Diseases
      Symposium director, Congress of Clinical Rheumatology

    Disclosures: McLain reports no relevant financial disclosures.