Maggie L. Shaw

Since the European League Against Rheumatism’s (EULAR) initial recommendations in 2010 for how to manage rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs (DMARDs), progress in the field necessitated 2 updates in 2013 and 2016. A third update was just released in the 

With clinical remission the main goal of RA treatment, using DMARDs enables symptom relief; improves physical function, quality of life, and social/work capacity; and inhibits structural damage to cartilage and bone.

This most recent update comprises 5 principles and 12 recommendations on the use of DMARDs—conventional synthetic (cs; methotrexate, leflunomide, sulfasalazine), biological (b; tumour necrosis factor [TNF] inhibitors [adalimumab, certolizumab pegol, etanercept, golimumab, infliximab], abatacept, rituximab, tocilizumab, sarilumab), 

, and targeted synthetic (ts; Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib)—and glucocorticoids to treat patients with RA. Included is guidance on mono- and combination therapies, treatment strategies, and tapering treatment. Altogether, this update considers patient benefits, safety, preferences, and costs related to RA treatment.

The 5 principles build on the previous updates, but they are not based on “specific scientific evidence.” Instead, they are overarching and address treating patients with RA:

Treatment should aim to provide the best care that is based on shared decision-making between patient and rheumatologist.

Treatment decisions should be based on disease activity, safety issues, and other patient factors (eg, comorbidities, disease progress, etc).

Rheumatologists should be the primary treating specialist for patients with RA.

Patients’ require and need access to different RA drugs throughout their lives, because the disease is heterogenous and may require a switch to a drug with a different mode of action.

Treating rheumatologists should consider the economic burden patients face when making therapeutic decisions.

The 12 recommendations also incorporate information from the previous updates. However, unlike the principles, they should be followed in this order:

Start DMARD therapy immediately following an RA diagnosis.

Make sustained remission or low disease activity the goal of treatment.

Monitor treatment on a regular basis and adjust as needed.

Incorporate methotrexate in a patient’s initial treatment; it also remains effective in combination with csDMARDs, bDMARDs, and tsDMARDs.

Consider leflunomide or sulfasalazine for initial treatment if methotrexate is contraindicated or a patient exhibits intolerance to it.

Consider short-term glucocorticoids if initiating/changing csDMARDS, but taper as soon as possible.

Switch to another csDMARD if the treatment goal is not reached with the first csDMARD.

Add a bDMARD or tsDMARD to csDMARD therapy if treatment goal is not reached and the patient has a poor prognosis.

Replace csDMARDs with interleukin-6 inhibitors or tsDMARDs when patients cannot use the former.

Incorporate one bDMARD/tsDMARD for another if treatment fails with the initial choice, but for TNF inhibitors that fail, there is a choice to introduce another agent or TNF inhibitor into the treatment regimen.

Scale back on bDMARDs or tsDMARDs in cases of persistent remission, after having already tapered glucocorticoids and when combination treatment includes a csDMARD.

Weight the decision to taper csDMARDs in cases of persistent remission.

These updated guidelines come on the heels of several new drug approvals in Europe after the 2016 update, and several of the principles and recommendations remain unchanged. However, the authors expect them to be revised again, and soon, so that patients can continue to receive optimal treatment from their treating rheumatologists and other stakeholders remain updated on progress in the field.

“We have reached a steady state of the evidence base for patients with established RA, although still some needs remain unmet, including the need to cure the disease. With the current rate of evidence development, we expect an update of the recommendations to be necessary in about 3-4 years,” they concluded.

Smolen JS, Landewé, RB, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update [published online January 22, 2020]. 

Articles

Updated guidelines from the European League Against Rheumatism (EULAR), based on new evidence and a review of the literature from 2016 to 2018, address recommendations on the use of disease-modifying antirheumatic drugs and glucocorticoids to treat patients with rheumatoid arthritis (RA). Included is guidance on mono- and combination therapies, treatment strategies, and tapering treatment.
 

Updated EULAR RA Treatment Recommendations Address Patient Concerns, Recent Developments

Seventy-one percent. That is how much the value of the global 

 (MS) drug market is expected to expand between 2016 and 2025: from $16.3 billion to $27.8 billion (USD). Costs per patient per year (PPPY) have risen, too, almost 7X over the past 20 years. Between 1993 and 2014, PPPY costs rose from $9000 to $60,000 (USD). Biosimilars, less expensive but having equivalent efficacy to their innovator biologics, can alleviate some of this spend. However, is the pharmaceutical industry putting patient safety at risk by rushing MS biosimilars to market?

That is the issue at heart in a recent commentary in the journal, 

, distinguished emeritus professor and founder and inaugural director, 

Maxine Mesinger MS Comprehensive Care Center

, Baylor College of Medicine. Rivera, now retired from active direction of the center, focuses much of his time on MS education.

 and how biosimilars are approved, in his opinion, without hard (ie, trial results) proof they actually are similar to their innovator biologic medicines, or are even cost-effective. In Iran, for example, where 101.19 persons per 100,000 have MS, 

 produced biosimilar interferon 1-a and 1-b were approved by the country’s Food and Drug Organization based on limited study results.

“The main priority should always be the protection and well-being of the patient irrespectively of therapy availability or pharmacoeconomic issues,” Rivera noted. “Theoretically, an ideal licensing acquisition would be that each proposed medication presented by the developer or the manufacturing company to the responsible authorities, should provide significant efficacy and safety results based on evidence, obtained through appropriate basic studies and well-designed clinical controlled trials.”

However, he sees the pharmaceutical industry motivated by money above all else, due to “loose national and international legislative control” that has raised the eyebrows of the MS field.

an especially concerning issue in Latin America

. At present, 9 follow-on β-interferons are vying for a share of the market against 3 interferon innovator products, Rivera notes. And their approvals have gone largely unchallenged by any regional licensing agencies. Just Brazil, Chile, Colombia, Panama, and Venezuela have legislation regarding biosimilars. In contrast, no MS biosimilars have been approved by the FDA, European Medicines Agency, the Japans Pharmaceuticals and Medical Devices Agency, or the UK Medicines and Healthcare Products Regulatory Agency.

The best possible solution right now, Rivera concludes, encompasses the following areas:

National and international studies that prove biosimilar similarity to innovator drugs

Providing education on biosimilars to anyone responsible for licensing them

“The patient’s well-being and safety remain as the fundamental principles in treating MS,” he emphasizes.

have suggested that some studies generally undertaken to facilitate biosimilar approval are unnecessary or even unethical in nature.

Rivera VM. Biosimilar drugs for multiple sclerosis: an unmet international need or a regulatory risk? 

2019;8(2):177-184. doi: 10.1007/s40120-019-0145-0.

A recently published commentary examines the global multiple sclerosis (MS) drug market from the perspective of patients and physicians, noting that different regulatory bodies have different standards in place for approvals, and questions if safety concerns are being addressed.

Commentary Questions Differing Global Standards for MS Biosimilar Approvals

, Kathy Oubre, MS, chief operating officer of Pontchartrain Cancer Center in Louisiana, decried the refusal of many insurance payers to add oncology biosimilars to their drug formularies. The cost is steep, she claimed: Patient health is at stake.

The costs of cancer care today have far-reaching implications, with the effects of the high prices of biologic medications inserting themselves in all facets of patient life. 

 often do not fill critically needed prescriptions, bypass important diagnostic tests altogether, or fail to even make appointments to see their healthcare providers, Oubre pointed out. But there are solutions that enable easier access to care.

. These lower-cost alternatives are interchangeable to reference biologics because they “can be expected to produce the same clinical result as the reference product in any given patient.” And healthcare providers, and their patients, should have ready access to this more affordable treatment option.

Instead, biologic originator medications continue to be preferentially prescribed, often due to “anticompetitive rebating practices,” Oubre 

. “Where biosimilars, which are certified as clinically equivalent by the FDA, are the correct treatment option, failure to prescribe them is a failure to address financial toxicity.” This toxicity amounted to an almost 75% increase in 2018 net spending on biologics.

These “fail-first” policies amount to insurers effectively eliminating the lower-cost biosimilars as a treatment option for patients to choose over their more expensive originator biologics. And manufacturers are using questionable rebating practices to force this choice. Last summer, the Federal Trade Commission 

 an investigation into the contracting practices of Johnson & Johnson’s for infliximab originator, and auto-immune drug, Remicade.

Despite claims that rebates benefit their insured populations as a whole, insurers avoiding the competition of biosimilars by not even providing them as an option does nothing to stem long-term price growth. And with more and more oncology biosimilars entering the market, healthcare providers should be able to help their patients reduce their out-of-pockets costs while providing the highest-quality care available, which will lead to savings over time. It’s simply a matter of being able to provide the choice, she wrote.

With the FDA’s updated guidance allowing pharmacists to substitute biosimilars for originator biologics, as they can for small-molecule generics and their brand name counterparts, progress is being made. In October, UnitedHealthcare even 

 biosimilar bevacizumab (Mvasi) and biosimilar trastuzumab (Kanjinti) to its lists of preferred products for commercial and community plans. But much remains to be done.

“The oncology provider community should demand better, making clear that antibiosimilar formulary policies infringe on providers’ ability to offer care in a manner that promotes the best outcomes for our patients,” Oubre emphasized. “Biosimilars may hold the key to savings for patients struggling with financial toxicity.”

In May 2019, the FDA released its final guidance on biosimilars. With more and more oncology biosimilars entering the market, healthcare providers should be able to help their patients reduce their out-of-pockets costs while providing the highest-quality care available, which will lead to savings over time, according to a recent column in Evidence-Based Oncology™, a sister publication to The American Journal of Managed Care®.
 

The Biosimilar Solution to Expensive Cancer Care

Indian private equity firm True North could soon hold a 2.44% minority stake in Biocon Biologics, after its planned merger with Biocon Research, parent company Biocon Ltd 

 in a statement. This is thanks to a $100-million investment approved by the Biocon Biologics Ltd board, which values Biocon Biologics at close to $3 billion. The investment is pending regulatory approval.

“This investment is an endorsement of the value that Biocon Biologics has demonstrated as a global biosimilars player, having commercialized three of its molecules in developed markets like EU, U.S., Japan and Australia,” 

 Kiran Mazumdar-Shaw, MD, chairperson and managing director, Biocon.

True North has invested in Biocon twice before. In 2014, when it was known as India Value Fund Advisors, the fund acquired an almost 10% stake in Syngene, Biocon’s contract research arm, and in 2003, it invested in Biocon in a pre-IPO round (the company went public in 2004).

“Biosimilars is a fast growing industry that addresses a fundamental need of bringing affordability to specialized effective biologic products. Biocon Biologics has been one of the global leaders with their early success in developing and commercializing multiple products across geographies,” added Satish Chander, partner, True North.

 in a new round of fundraising in 2020 that could bring in $200 million to $300 million for Biocon Biologics. Other potential investors include 

, a Singapore government-owned investment firm, and 

, the UK government’s investment arm. The Biologics arm of Biocon has seen enormous growth since it was formed in 2017, and it is on target to hit $1 billion in revenue in fiscal year 2022.

Thanks to its partnership with Mylan, Biocon received its first FDA approval in 2017 for the biosimilar trastuzumab, Ogivri, which recently became 

 in the United States. The biosimilar pegfilgrastim, Fulphila—the first biosimilar to pegfilgrastim available in the United States&mdash;was approved in 2018, and Biocon’s manufacturing facility for it this past November. Altogether, Mylan and Biocon Biologics have produced 11 molecules.

Indian private equity firm True North could soon hold a 2.44% minority stake in Biocon Biologics India Ltd, a subsidiary of Biocon Ltd, thanks to a $100-million investment. The influx of cash values Biocon Biologics at close to $3 billion. The investment is pending regulatory approval.

Maggie L. Shaw

Updated EULAR RA Treatment Recommendations Address Patient Concerns, Recent Developments

Commentary Questions Differing Global Standards for MS Biosimilar Approvals

The Biosimilar Solution to Expensive Cancer Care

True North $100-Million Investment in Biocon Biologics Kicks Off New Fundraising Round