Lana Dykes

This article was originally published in 

The US Food and Drug Administration (FDA) has approved the citrate-free, high-concentration (100 mg/mL) formulation of adalimumab-bwwd (HADLIMA), a biosimilar of adalimumab (HUMIRA), for the treatment of 

, juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and Crohn’s disease.

The approval was announced by Samsung Bioepis and Organon for the high-concentration version of adalimumab-bwwd, the first approved by the FDA as a low-concentration (50 mg/mL) dose in July 2019. The biosimilar will be available in both autoinjector and pre-filled syringe options.

The FDA’s decision was based on a randomized, single-blind, two-arm, parallel group, single-dose study that evaluated the safety, tolerability, immunogenicity, and pharmacokinetics of adalimumab-bwwd 50 mg/mL and adalimumab-bwwd 100 mg/mL in healthy male subjects (n = 188; mean age 38.4 years).

Immunogenicity, assessed by the occurrence of anti-drug antibodies and neutralizing antibodies, was comparable between both treatment arms. The mean values and ranges of pharmacokinetics parameters, tolerability, and treatment-emergent adverse events (TEAEs) were similar for both low- and high-concentration cohorts.

In addition, the most common TEAEs were upper respiratory infection, sinusitis, injection site reactions, headaches, and rash, while no TEAE led to study discontinuation and all reported events were mild or moderate in severity.

“With this approval, we now have both a low and high concentration adalimumab biosimilar approved by the FDA, marking an important step towards expanding treatment options for patients suffering from certain chronic, autoimmune diseases,” Byoungin Jung, Vice President and Regulatory Affairs Team Leader, Samsung Bioepis, stated. “By leveraging our development expertise, manufacturing excellence and supply chain reliability, we will continue our work to ensure healthcare systems have more affordable treatment options available.”

Articles

The treatment is indicated for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and Crohn’s disease. 

FDA Approves Adalimumab Biosimilar

This article was originally published on 

Elevated serum interleukin-23 (IL-23) levels in patients with 

, anxiety, and disease activity, according to a study published in 

“Psoriatic disease is frequently limited to the core clinical domains of skin psoriasis, nail involvement, peripheral inflammatory arthritis, axial spondyloarthritis, enthesitis, and dactylitis, while its numerous systemic consequences and comorbidities are ignored,” investigators explained. “The psychosocial burden of PsA has been shown to have a negative effect on the quality of life of the patients. In PsA, psychological disorders can both cause and exacerbate disease development.”

In this observational case-control study, 80 patients with PsA, meeting the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria, and 80 healthy volunteers were matched for age and gender. Information collected included disease history, a clinical assessment, a Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the Psoriasis Area and Severity Index (PASI), and ultrasonographic entheses according to the Madrid Sonographic Enthesitis Index (MASEI). Depression and anxiety were evaluated by the Hospital Anxiety and Depression Scale (HADS). IL-23 was measured and compared with disease activity, depression, and anxiety.

A difference between patients and controls regarding demographic data was not reported. The mean duration of PsA was 6.94 years and the mean duration of psoriasis symptoms was 10.43 years. In total, 36 patients with PsA reported anxiety (45%) and 28 patients experienced depression (35%), compared with the control group who reported significantly less anxiety (n = 16, 20%) and depression (n = 12, 15%). HADS anxiety and depression scores were positively correlated between HADS depression (

: 0.001) scores (p < 0.05). IL-23 was positively linked to DAPSA, PASI, and HADS scores. Additionally, IL-23, DAPSA, and PASI scores were independently associated with depression and anxiety.

Patients who were not responding to treatment (n = 22) were significantly more likely to experience anxiety (n = 20, 90.9%) compared with treatment responders (n = 16, 27.6%). Non-responders were also more likely to report depression (n = 16, 72.7%) compared with treatment responders (n = 12, 20.7%).

The single-centered, cross-sectional study design limited results as did the small number of participants. Future longitudinal studies may be necessary to evaluate the relation between IL-23 and depression, anxiety, and disease activity. Confounding factors regarding depression and anxiety during the COVID-19 pandemic and its effect on psychological status are unknown.

“PsA is a chronic progressive inflammatory condition, involving peripheral arthritis and/or spondylitis associated with psoriasis,” investigators concluded. “PsA also affects mental health. Serum interleukin-23 levels were elevated in PsA patients and were found to be correlated with depression, anxiety, and disease activity.”

Serum interleukin-23 levels: relation to depression, anxiety, and disease activity in psoriatic arthritis patients

Patients with psoriatic arthritis (PsA) who have elevated interleukin-23 (IL-23) levels have been linked to higher rates of depression, anxiety, and disease activity.

Elevated IL-23 Levels in PsA Patients are Associated with Depression, Anxiety

Results from a University of Bristol-led analysis of a phase 3 trial are providing clinicians with insight into use of baricitinib in the management of 

The study, led by Athimalaipet Ramanan, FRCPCH, FRCP, of Bristol Royal Hospital for Children at Bristol Medical School, assessed data from the JUVE-BASIS trial, suggests baricitinib significantly reduced both the time to and frequency of flares in patients with JIA when compared with placebo (PBO), with improvements in JIA-ACR scores observed in the majority of patients by week 12.

“Baricitinib is a Janus kinase (JAK)1/2 selective inhibitor approved for the treatment of rheumatoid arthritis,” investigators explained. “JIA is a group of diseases characterized by immune mediated chronic arthritis which often requires treatment with conventional synthetic or biologic disease-modifying antirheumatic drugs (cs or b-DMARDs).

To investigate efficacy and safety of baricitinib in patients with JIA with an inadequate response to cs or b-DMARDs, patients aged 2 to <18 years with extended oligo- or poly-articular JIA, enthesitis-related arthritis (ERA), or juvenile psoriatic arthritis (JPsA) were included in the multicenter, double-blind, withdrawal study (

). Eligible patients met International League of Associations for Rheumatology (ILAR) criteria and had an inadequate response to 1 or more cs and/or b-DMARDs.

The study was categorized into 3 periods: a 2-week pharmacokinetic/safety assessment (PKS), a 12-week open-label lead-in (OLLI), and an up-to a 32-week double-blind withdrawal (DBW) period. Both dosage and safety were established in the PKS first, and then all patients, including those enrolled in the OLLI who were receiving age-based, oral, once daily doses of baricitinib. Those with a JIA-ACR30 response at week 12, the end of OLLI, were then entered into the DBW and randomized 1:1 to either continue baricitinib or begin PBO, remaining until flare or up to week 32. The primary endpoint was time to flare during the withdrawal period. Secondary endpoints included the JIA-ACR30/50/70/90 response at week 12, as well as the proportion of patients who experienced a flare during the DBW.

Of the 220 patients were enrolled in the study, with 29 in the PKS group, 219 entered the OLLI, and 163 participated in the DBW. The JIA-ACR30/50/70/90 response at week 12 was 76.3%, 63.5%, 46.1%, and 20.1%, respectively. Time was significantly shorter with PBO compared with baricitinib (hazard ratio 0.24 [95% CI 0.13,0.45], 

<0.001) and flares were significantly lower in patients receiving baricitinib when compared with placebo (14 (17.1%) vs 41 (50.6%), 

During the PKS and OLLI periods, 57.3% (n=126) of patients reported 1 or more treatment emergent adverse event (TEAE), and 2.7% (n=6) of patients had 1 or more serious adverse event (SAE). In the DBW period, 46.9% (n=38) patients receiving placebo and 65.9% (n=54) patients receiving baricitinib reported at least 1 TEAE, and 3.7% (n=3). A total of 4.9% (n=4) reported 1 or more SAE, respectively. The mean weeks of exposure was higher in participants in the baricitinib group when compared with placebo during DBW (26.34 vs 18.91, respectively) due to the study design. There were no deaths, cardiovascular events, or uveitis, and safety was consistent with the known safety profile in adult patients with rheumatoid arthritis.

“These findings support baricitinib as a treatment for signs and symptoms of JIA with an inadequate response to cs or b-DMARDs,” investigators concluded.

Baricitinib in Juvenile Idiopathic Arthritis: A Phase 3, Double-Blind, Placebo-Controlled, Withdrawal, Efficacy and Safety Study

Data suggests baricitinib not only significantly reduced the time to flares but also the frequency of flares in patients with JIA when compared with placebo.

Juvenile Idiopathic Arthritis Flares Are Reduced in Patients Treated with Baricitinib

Filip Van den Bosch, MD, discussed his 

European Alliance of Associations for Rheumatology (EULAR) 2022 conference

 presentation, “Efficacy and Safety of Upadacitinib in Patients With Active 

: a Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial” in an interview with 

Van den Bosch is Head-of-Clinic and Associate Professor of Rheumatology in the Department of Rheumatology at the University Hospital of Ghent University.

The SELECT-AXIS 2 program was conducted to assess the efficacy and safety of upadacitinib compared with placebo on reduction of signs and symptoms in adults with active axial spondyloarthritis (axSpA) 

The primary endpoint for the SELECT-AXIS 2 program was the Assessment in Spondylo-Arthritis international Society (ASAS) 40 response at week 14. 

“The ASAS score can be used by physicians to measure whether a patient’s condition has improved and ASAS disease areas assessed include back pain, patient global assessment of disease activity, functional limitation​, and morning stiffness,” Van den Bosch explained. 

Secondary endpoints evaluated at week 14 were improvements from baseline in disease activity, pain, function, inflammation, spinal mobility, enthesitis, and health-related quality of life.

Results from the SELECT-AXIS 2 nr-axSpA study found upadacitinib demonstrated significantly greater improvements in signs and symptoms, pain, function, disease activity, and MRI-detected spine inflammation with upadacitinib compared to placebo at week 14. Significantly more nr-axSpA patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib versus placebo (45 percent versus 23 percent; P<0.0001).

 What is the clinical significance of these results?

 The data obtained from the SELECT-AXIS 2 program reinforce the potential of upadacitinib to be a meaningful treatment option for patients across the spectrum of axSpA. These data suggest upadacitinib, an oral therapy, has the potential to help counter inflammation, relieve pain and improve function, helping patients living with nr-axSpA take control of their disease.

 Does your team plan on doing any further research on this drug regarding nr-axSpA/AS?

 We’re continuing to conduct research across the spectrum of axSpA to reinforce the potential of upadacitinib to be a meaningful treatment option for patients. The SELECT-AXIS 2 studies are ongoing and currently have data through two years in patients with axSpA.

 Is there anything else you’d like our audience to know?

 There is an unmet need in axSpA with gaps in diagnosis and disease management. AxSpA can be difficult to test for, often resulting in delays in diagnosis, leading to a nine-year average period between symptom onset and AS diagnosis. Early, effective, and comprehensive disease management of axSpA is key to reducing the risk of functional disability and to improving health outcomes.

The phase 3 research being presented at the EULAR 2022 conference evaluated the efficacy and safety of upadacitinib in patients with active non-radiographic axial spondyloarthritis.