Frieda Wiley, PharmD

A new study shows that the clinical status of patients who have either rheumatoid arthritis or axial spondyloarthritis, can be successfully maintained when switching from the biologic originator etanercept to a biosimilar called SB4.

Using real-world evidence collated from four countries in the European Union, the “BENEFIT” Pan-European Observational Study elucidates the efficacy and safety profile of the transition from the original biological drug etanercept to a biosimilar in populations of patients who have rheumatoid arthritis or axial spondyloarthritis.

The biosimilar, SB4, received marketing approval from the EU based on the data presented derived from pre-clinical, phase I and phase III studies in 2016. According to the data in these studies, SB4 exhibited efficacy and bioequivalence as well as comparable safety and immunogenicity profiles of similar measures to etanercept. 

The study's authors emphasized the significance of collecting real-world data by transcending the controlled environment of a randomized clinical trial. By investigating outcomes in a real-world setting, investigators were able to gain insight into the practice perspective regarding transition logistics and outcomes associated with switching therapies in a standard clinical practice setting.

The observational study followed 557 patients, 358 with rheumatoid arthritis and 199 with axial spondyloarthritis in a real-world setting. Of these patients, rheumatoid arthritis patients averaged 60.9% (SD 11.09) years of age, while the mean of axial spondyloarthritis patients was 39.9 (13.3) years. Nearly three-fourths of the patients followed who had rheumatoid arthritis were women, averaging 73.3% or 264 of the population; slightly more than one-fourth of the patients in the axial spondyloarthritis arm (27.1%) were women.

Among the inclusion criteria were having rheumatoid arthritis or axial spondyloarthritis and having initiated SB4 therapy after having been reached a stable dose of etanercept within a period of six months.

Researchers retrieved data from clinical records both retrospectively dating back six months prior and prospectively and/or retrospectively six months for a six-month period following the etanercept to SB4 switch. The following endpoints were followed: disease score (noted as disease activity score calculator for rheumatoid arthritis (DAS-28)) for rheumatoid arthritis, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for axSpA) over time, clinical characteristics and management, and serious adverse events.

Rheumatoid Arthritis patients averaged a DAS-28 score of 2.0 (SD 0.84) six months prior to transition to SB4, while axial spondyloarthritis averaged 2.5 (SD 1.93). Disease score values at six months post-transition to SB4 individual changes in disease scores from baseline to six months post-transition were negligible (0.0 (SD 0.81 for RA patients) and (2.3 (1.81) for axial spondyloarthritis patients)).

Only one adverse event-pneumonia-was reported as a serious adverse event and linked to SB4. The other six adverse events reported were not related to SB4. These were uveitis, chronic obstructive pulmonary disease, umbilical hernia, lithium overdose, and relapsing pancreatitis.

"‘BENEFIT’ Pan-European Observational Study to Evaluate the Real-world Effectiveness of SB4 Transition from Originator Etanercept (ETN) in Patients with Rheumatoid Arthritis or Axial Spondyloarthritis: A Switch Success Story.

 ACR/ARP Annual Meeting, November 8-13, Georgia World Congress Center, Atlanta, GA

Articles

A new study shows that the clinical status of patients who have either rheumatoid arthritis or axial spondyloarthritis, can be successfully maintained when switching from the biologic originator etanercept to a biosimilar called SB4.

Trial Shows Switch from Etanercept Biologic to Biosimilar Maintains Clinical Outcomes

Patients who have systemic sclerosis-associated interstitial lung disease and received nintedanib were more likely to have improved lung function than patients who received a placebo, according to a new study. Not only did nintedanib improve forced vital capacity, but patients who received the drug were less likely to experience declining clinical status and more likely to see their conditions stabilize.

Systemic sclerosis (SSc) is a rare autoimmune disorder that affects connective tissue, noted by various clinical features such as vasculopathy, abnormal activity of the immune system, cellular inflammation, vasculopathy, and fibrosis of internal organs as well as the skin. Systemic sclerosis can also affect the lungs. Not only is interstitial lung disease (ILD) frequently observed in these patients, but it is also a leading cause of death.

Clinicians routinely measure mean change in forced vital capacity to help them evaluate outcomes in treatment-related outcomes in patients who have interstitial lung disease as well as those who have SSc-ILD, but they must also determine the clinical relevance of the forced vital capacity value based on the degree by which forced vital capacity changes. Previous research conducted on using either cyclophosphamide or mycophenolate mofetil versus placebo produced results of minimal clinical importance, noted by either forced vital capacity improvement of at least three percent or deterioration of -3.3 percent.

In a new phase III randomized, double-blind, placebo-controlled parallel-group trial known as SENSCIS, researchers investigated the effects of administering nintedanib 150 mg twice daily versus placebo in patients who have SSc-ILD.  In this study, SSc-ILD was defined as having at least 10 percent lung fibrosis with a baseline forced vital capacity of greater than 40 percent and a DLCO that ranged from 30-89 percent of the predicted value. Researchers included data from 575 patients with comparable baseline characteristics who were randomized one to one to receive either oral nintedanib or placebo.

After 52 weeks, 66 of the 287 patients who received nintedanib (23 percent), experienced a 3 percent or greater improvement in their forced vital capacity. Of the placebo group, 43/288, or 15 percent of patients experienced similar improvements (OR 1.69; 95% ci 1.11-2.59; P=0.014). The number of patients in the interventional group who either had improved forced vital capacity or stabilized symptoms ( (66% vs. 56%; OR 1.52; 95% CI 1.08–2.13; P=0.015) was significantly greater than that of the placebo arm. Moreover, the number of patients in the nintedanib arm whose clinical status worsened was significantly lower than the placebo arm (34% vs. 44%; OR 0.66; 95% CI 0.47–0.92; P=0.015).

"Improvement and Stabilization of Lung Function in Patients with SSc-ILD Treated with Nintedanib vs Placebo in a Randomized, Placebo-Controlled Phase III Trial: Proportions of Patients with FVC Changes Using Cutoffs Previously Proposed to Define Minimally Clinically Important Differences." 

Ninfetanib Improves and Stabilizes Lung Function in Systemic Sclerosis

Scientists now have a better understanding of the relationship between the gut microbiome and rheumatoid arthritis.

By utilizing case-controlled associated tests, Japanese researchers conducted a whole-genome shotgun sequencing-based, metagenome-wide association study (MWAS). They identified high concentrations of numerous species belonging to the Prevotella genus.

By employing a combination of case-control tactics and artificial intelligence, researchers traced an association between the gut microbiome, host genome, and pathology of rheumatoid arthritis. Researchers identified a population-specific link between the metagenome and the host genome.

Researchers conducted a MWAS on the rheumatoid arthritis gut microbiome in a sample population of 82 patients (42 control). They then combined the results of phylogenetic case-control association tests and artificial intelligence results derived from non-linear machine learning to better elucidate the phyologenetic tree associated with rheumatoid arthritis pathology.

Gaining better insights into the phylogenetic lineage was a critical step to better understanding the etiology associated with the disease’s microbiome.

Using case-controlled associated tests made it possible for researchers to identify high concentrations of numerous species belonging to the Prevotella genus; next, they employed non-linear machine learning strategies-a task which proved advantageous by allowing them to rule out any potential phylogenetic discrepancies.

From there, researchers were able to identify one redox reaction-related gene that appeared in significantly lower abundance in the RA metagenome as opposed to in controls. The case-control comparison also facilitated the ability to bring clarity to fatty acid biosynthesis, glycosamine degradation, and various other pathways involved in metabolism.

The pathogenic mechanism of the microbiome remains largely unelucidated in many diseases, and this research sheds new light on the microbiome composition and its involvement in rheumatoid arthritis pathology by engaging MWAS to access three primary bioinformatic analytic pipelines.

Metagenome-Wide Association Study of Gut Microbiome Revealed Novel Etiology of Rheumatoid Arthritis in Japanese Population

. ACR/ARP Annual Meeting, November 8-13, Georgia World Congress Center, Atlanta, GA

Author | Frieda Wiley, PharmD

Articles

Trial Shows Switch from Etanercept Biologic to Biosimilar Maintains Clinical Outcomes

Ninfetanib Improves and Stabilizes Lung Function in Systemic Sclerosis

New Etiology of Rheumatoid Arthritis Identified in the Gut Microbiome