Practice

The potential for the development of antidrug antibodies is a key concern among prescribers who use all biologics that target tumor necrosis factor (TNF). Two presentations at the American College of Rheumatology Annual Meeting in Chicago, Illinois, which will be held from October 19-24, 2018, will address the immunogenicity of biosimilars in patients with rheumatoid arthritis and other inflammatory diseases.

As biosimilar etanercept SB4, sold in many markets as Benepali, has entered the rheumatoid arthritis treatment space, researchers have recognized the need to investigate the retention rates and disease activity scores among patients receiving SB4 and its reference.

A recent study provides insight into the feasibility of at-home administration of biosimilar filgrastim—Pfizer’s recently approved Nivestym—an option that has the potential to reduce patient burden associated with hospital administration.

Stakeholders hoping to see increased uptake of biosimilars in the United States are increasingly pointing to a lack of provider awareness as a key hindrance to the biosimilars marketplace. New research, to be presented at the American College of Rheumatology Annual Meeting in Chicago, Illinois, held from October 19-24, 2018, suggests that, despite efforts to educate providers, awareness of biosimilars—as well as awareness of patients’ attitudes toward them—remains low.

As more biosimilars are poised to become available to US patients, American rheumatologists are looking to their European counterparts for lessons learned from nonmedical switches from reference products to biosimilars. During the American College of Rheumatology (ACR) Annual Meeting in Chicago, Illinois, held from October 19-24, 2018, several research teams will present on nonmedical switching in the European context.

Pemphigus vulgaris (PV) is a rare immune-mediated skin disorder, typically occurring in middle-aged and older adults, that involves painful blistering of the skin and mucous membranes. While many patients are well controlled on systemic corticosteroid treatment, steroid-sparing therapy can be desirable for treating moderate to severe forms of the disease, and rituximab is one such agent to show promise in this indication.

Kashyap Patel, MD, a medical oncologist at Carolina Blood and Cancer Care, said after the FDA’s Oncologic Drug Advisory Committee (ODAC) hearing on CT-P10 that "Clearly, the mood has changed to be a lot more favorable for the biosimilars.”

According to the authors, the medical literature points to 3 key triggers of the nocebo effect, all of which offer possible solutions to overcoming the nocebo effect in switches to biosimilars.

Infliximab accounts for substantial drug spending in the United States, and dose rounding has become a common practice at many facilities as a way to avoid wasting vials that have only been partially used. However, many institutions do not have standardized approaches to rounding doses, and because infliximab requires a weight-based dose, rounding becomes even more complex.

Health Canada has approved a formulation of Roche’s originator trastuzumab, Herceptin, that is intended for subcutaneous administration. The drug, indicated to treat HER2-positive cancers, can be administered in 2 to 5 minutes (versus an average of 90 minutes for intravenous administration).

In explaining why some patients who switch to biosimilars from reference biologics discontinue their therapy at a higher rate than those who remain on a therapy without interruption, some authors have referenced the so-called “nocebo” effect. This effect, whereby a patient experiences disease worsening or adverse events due to negative beliefs about a drug, has been controversial, however, and not all clinicians agree that the effect is to blame for differences in discontinuation.

In recent years, payers in Europe have been increasing their scrutiny of new therapies as increasingly high-cost drugs come to the market. And while the United States does not have the same cost constraints as the single-payer health systems, it too faces heightened pressures to lower costs in order to afford innovative therapies.

Fraser Cummings, MBChB, DPhil, led one of the first clinical teams to switch patients receiving the reference infliximab (Remicade) to CT-P13 (Remsima) in UK clinical practice. During the SMi 9th annual conference on Biosimilars and Biobetters, held September 26-27 in London, United Kingdom, Cummings explained his experience with this switch in his gastroenterology clinic, and looked ahead to the arrival of adalimumab biosimilars in the National Health Service (NHS).

The National Health Service’s (NHS) Specialist Pharmacy Service released resources for clinicians to use with patients in the discussions around switching from the reference Humira to a biosimilar.

The latest review seeking to reassure clinicians about the safety of switching their patients to biosimilars focuses on rheumatology indications.

The risk evaluation and mitigation strategy program for clozapine allows for patients to receive clozapine—even in the setting of moderate to severe neutropenia—if the benefit to psychiatric treatment outweighs the risk of recurrent neutropenia. However, literature that can guide appropriate treatment for such patients is limited. A recently published case report suggests that using filgrastim to control leukopenia and neutropenia could allow patients to continue to receive clozapine without interruption.

Treating ankylosing spondylitis (AS) is costly, even in high-income nations. In lower-income countries, patients may face serious challenges in accessing high-cost drugs, like anti–tumor necrosis factor agents, even when biosimilars are available.

During the 20th Asia Pacific League of Associations for Rheumatology (APLAR) Congress, held September 6 to 9 in Kaohsiung, Taiwan, researchers presented on real-world experience with switching to biosimilars in treating rheumatic diseases.

Rituximab-based immunochemotherapy can be safely applied in patients after obinutuzumab-associated anaphylaxis, but the existing risk of cross­reactivity should be considered, and careful monitoring of such patients during rituximab infusion is required.

A new study suggests that CD8+ natural killer cells are a biomarker that can predict therapeutic outcome for patients with ankylosing spondylitis who are administered anti–tumor necrosis factor agents because they are nonresponsive to conventional treatment.

Adherence and persistence rates for biologic drugs are still low in the United States, leading to suboptimal patient outcomes and putting a substantial burden on the healthcare system.

Two pivotal studies of biosimilar epoetin alfa (Retacrit) versus its reference (Epogen) in patients undergoing hemodialysis have shown that the biosimilar and the originator have comparable safety and efficacy. In the phase 3b PIEDA (Phase 3b Investigation of Erythropoietin Drugs Using a Specified Dosing Algorithm) study, investigators sought to further investigate how switching from the reference to the biosimilar affects maintenance of hemoglobin levels when using an erythropoiesis-stimulating agent dosing algorithm.

While both the biosimilar filgrastim and biosimilar pegfilgrastim were effective in reducing the incidence of neutropenia, adverse events related to granulocyte-colony stimulating factor therapy were significantly higher in patients who received pegfilgrastim.

Currently, UK eligibility criteria for starting biologics in patients with rheumatoid arthritis (RA) set a threshold of a disease activity score in a count of 28 joints of 5.1 or higher—the threshold for severe disease—on at least 2 occasions measured 1 month apart.

Pediatric Crohn disease (CD), which can have serious impacts on children’s growth, is increasing in incidence. Current treatments for pediatric patients with CD—such as corticosteroids or immunomodulators—may be particularly difficult for children to tolerate. Infliximab, however, has been shown to be effective and well tolerated in children, as a newly published phase 3 study in Japanese pediatric patients with CD found that infliximab improved clinical outcome measures from week 2 to week 56.

Regulators licensed the 3 etanercept biosimilars discussed for all of the indications of the reference drug on the basis of the extrapolation of indications, a practice that the authors say rheumatologists may find “anomalous and a source of debate.”

There was a significant difference observed in pain scores between pediatric patients receiving pegfilgrastim versus those receiving filgrastim after allogenic hematopoietic stem cell transplantation.

Because patients with rheumatoid arthritis may have compromised manual dexterity, they may have challenges with self-administering their biologic therapies. In the case of etanercept, which is typically administered once per week, device design that prioritizes ease of use can help improve patient adherence to treatment regimens.

The researchers concluded that rituximab should be considered as a preferred biologic treatment for rheumatoid arthritis (RA) therapy, though treatment of RA with any biologic medication improved quality of life significantly.

In analyzing the association between biologic-free remission maintenance and the type of biologic drugs that patients had used, a notable difference emerged between patients who used infliximab, adalimumab, or golimumab versus those who received etanercept and certolizumab pegol.