Novel Therapies Mitigate High-Cost Rheumatoid Arthritis Treatment

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that characteristically affects the joints of the hands and feet, causing inflammation, swelling, pain, and progressive destruction of articular structures. RA affects about 1% of the population; onset may occur at any age but most often occurs between ages 35 and 50 years, according to The Lancet.

“The main treatment goals with rheumatoid arthritis are to control inflammation, relieve pain, and reduce associated disability,” said Julie Rubin, director of clinical services, CompleteRx. “Treatment usually includes medications, occupational or physical therapy, regular exercise, and in more extreme cases, surgery to correct joint damage.”

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Traditional medications for RA include nonsteroidal anti-inflammatories (NSAIDs) and steroids to help reduce inflammation, and disease-modifying anti-rheumatic drugs (DMARDs). “Methotrexate is the main therapy in the class of DMARDs but others include hydroxychloroquine, leflunomide, and sulfasalazine,” says Rubin.

Management and treatment strategies of RA has evolved over the last two decades due to the advent of biologics. Enbrel (etanercept, Amgen) was FDA approved in 1998, becoming the first biologic indicated for the treatment of RA. Since Enbrel, several other biologic medications have been approved for treatment of RA including Remicade (infliximab, Janssen), Humira (adalimumab, AbbVie), and Rituxan (rituximab, Genentech).

“Many of these drugs can be expensive, even with healthcare or Medicare coverage,” says Ashraf Shehata, advisory principal at KPMG and a member of the firm’s Global Healthcare Center of Excellence. “Higher out-of-pocket costs can be a compliance issue for patients and the high cost of these drugs tend to front load that burden on patients early in the year.”

New biologics

Actemra (tocilizumab, Roche), an interleukin-6 (IL-6) receptor antagonist.

• Approval January 2010 for the treatment of moderate-to-severe RA in patients who have had an inadequate response to one or more DMARD. Actemra was originally developed as an intravenous infusion followed by a subcutaneous formulation approved in 2013. Most recently, a prefilled autoinjector (ACTPen) was approved in November 2018 and is expected to be available early this year.

• Cost Intravenous solution: $131.04/mL; prefilled syringe (162 mg/mL): $1,186.66.

Xeljanz (tofacitinib, Pfizer), a JAK [Janus kinase] inhibitor.

• Approval November 2012 for the treatment of moderate-to-severe RA in adults who have had an inadequate response to, or are tolerant of, methotrexate. In February 2016, Xeljanz XR became the first once-daily oral JAK inhibitor for the treatment of RA and Xeljanz is the only JAK inhibitor included in the most recent American College of Rheumatology RA treatment guidelines from 2015.

• Cost Xeljanz XR 11-mg tablet: $164.83/tablet, Xeljanz 5-mg or 10-mg tablet: $81.91/tablet.

Kevzara (sarilumab, Sanofi and Regeneron), an IL-6 receptor antagonist.

• Approval May 2017 for the treatment of moderately to severely active RA in adults who have had an inadequate response or intolerance to one or more DMARD. Kevzara comes as a prefilled syringe or auto-injector and is dosed every two weeks as a subcutaneous injection, which can be self-administered.

• Cost Kevzara (150 mg/1.14 mL, 200 mg/1.14 mL): $1,552.63/mL.

Olumiant (baricitinib, Eli Lilly), a JAK inhibitor.

• Approval June 2018 for the treatment of adults with moderate-to-severe RA who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.

• Cost Olumiant 2-mg tablet: $82.19/tablet.

“There are a fair number of alternatives to help patients manage this condition,” says Shehata. “The biologic drugs are expensive, but they help keep the condition in check and could help avoid surgeries and disability costs.”

Biosimilars

“Biosimilars could take some of the sting from the costs of RA drugs and several are on the market,” says Shehata. “Health plans need to consider whether the convenience of JAK inhibitors, which are administered orally, adds more value than the savings from injectable biosimilars.”

Erelzi (etanercept-szzs), biosimilar to Enbrel (etanercept, Amgen), but not interchangeable with Enbrel.

• Approval August 2016, but U.S. launch is unknown due to patent disputes.

Amjevita (adalimumab-atto) and Cyltezo (adalimumab-adbm), both approved biosimilars to Humira (adalimumab, AbbVie).

• Approval Amjevita, September 2016, but under a settlement with AbbVie will not be marketed until 2023. Cyltezo, August 2017, but U.S. availability is currently unknown due to ongoing patent litigation.

Inflectra (infliximab-dyyb), bioimilar to Remicade (infliximab, Janssen).

• Approval April 2016.

• Cost Reconstituted 100-mg intravenous solution: $1,135.54/each.

Pipeline

Upadacitinib (AbbVie), an investigational, oral, JAK-1 selective inhibitor.

• Status Manufacturer submitted new drug application (NDA) to the FDA on December 20, 2018 for the treatment of adults with moderate-to-severe RA based on results of the SELECT phase 3 RA program studies.

​Olokizumab (R-Pharm), an investigational, subcutaneous, IL-6 antagonist

• Status Currently in phase 3 studies to assess efficacy and safety in patients with moderate-to-severe RA (CREDO-4); estimated study completion date: November 2021.

Filgotinib (Gilead and Galapagos), an investigational, oral, JAK-1 selective inhibitor

• Status Currently in a long-term extension study to assess the safety and efficacy in patients with RA (FINCH-4); estimated completion date: May 2022.

Erin Johanek, PharmD, RPh, is a staff pharmacist at Southwest General Health Center, Middleburg Heights, Ohio.