Evolving Strategies in RA Treatment: Real-World Insights and Access Challenges

This expert roundtable, hosted by First Report Managed Care, explores the evolving rheumatoid arthritis (RA) treatment landscape, highlighting advancements in therapeutic options, challenges with payer-driven access and reimbursement, and the real-world impact of biosimilars and agents like tocilizumab, through the clinical lens of Jonathan Kay, MD, and the practice management perspective of Julie Baak.

Read the full transcript below:

Juliet Gallagher: Welcome and thank you for joining us for today's expert roundtable, hosted by First Report Managed Care. I'm Juliet Gallagher, managing editor, and I'm thrilled to be moderating today's timely discussion on the rheumatoid arthritis (RA) treatment landscape, an area that continues to evolve rapidly with major implications for both clinical and payer decision-making.

I'm joined by 2 exceptional experts here. I'm going to ask you both to briefly introduce yourselves. Dr Kay, if you'd like to go first.

Jonathan Kay, MD: Thanks very much for having me. I'm Jonathan Kay. I am a professor of medicine and of population and quantitative health sciences at UMass Chan Medical School, where I hold the Timothy S. and Elaine L. Peterson chair in rheumatology.

Julie Baak: My name is Julie Baak. I'm the practice manager of the Arthritis Center in Bridgeton, Missouri, a private practice where I serve working class people and poor people.

Gallagher: Fantastic. Together we'll explore the RA treatment continuum, biosimilar adoption, payer coverage pressures, and real-world outcomes, including the evolving role of Actemra in this space.

To begin, let's discuss the current RA treatment landscape. We've seen a shift in prescribing trends over recent years with the broadening of treatment classes, payer-driven utilization management, and increased scrutiny on cost-effectiveness. Dr Kay, from your clinical perspective, how has the treatment landscape evolved, especially with regard to patient stratification and treatment sequencing?

Dr Kay: The treatment landscape for rheumatoid arthritis has evolved drastically over the past 25 years, and even more over the past 40, during the time I've practiced rheumatology. When I started in rheumatology, we had hydroxychloroquine, sulfasalazine, and intramuscular gold available to us, as well as corticosteroids.

In the late 1990s, etanercept and infliximab were the first 2 biologic medications, TNF inhibitors, that were introduced, followed shortly by adalimumab and then by certolizumab pegol and golimumab for a total of 5 TNF inhibitors. But then we had other medications that became available. We had abatacept, an inhibitor of T-cell costimulation, and then tocilizumab, which is an antibody against the interleukin-6 receptor; sarilumab became the second antibody against the interleukin-6 receptor. Rituximab is an antibody against CD20 antigen on the surface of B cells, which depletes B cells.

In addition to those medications, we now have oral medications. The JAK inhibitors—first tofacitinib, a relatively nonselective JAK inhibitor; then baricitinib, which is a JAK 1/JAK 2 selective agent; and upadacitinib, which is JAK 1 selective. We now have 10 targeted therapies directed against various aspects of the pathophysiology of rheumatoid arthritis.

Methotrexate, I failed to mention earlier, was introduced around the mid-1980s and it became the anchor drug for the treatment of rheumatoid arthritis. From the mid-1980s until now, methotrexate has really revolutionized the treatment of rheumatoid arthritis. Patients used to expect to destroy joints and require joint replacement surgery; now, hardly ever is a patient with rheumatoid arthritis referred to an orthopedic surgeon for total joint arthroplasty surgery. Methotrexate was initially used at low doses of 7.5 to maybe 12.5 or even 15 milligrams, but now we start at 15 milligrams, and we escalate the dose up to 25 milligrams weekly in divided doses of 12.5 milligrams each on one day of the week.

With methotrexate being ubiquitous as the anchor drug and the availability of the 10 targeted therapies that are usually added on to methotrexate, we have a much broader treatment landscape which is, in many cases, very effective for treating patients. Treatment sequencing, as I've alluded to, usually begins with the initiation of methotrexate therapy once a diagnosis of rheumatoid arthritis is made.

When methotrexate has been maximized, if disease remains active, TNF inhibitors are usually added as the first line of therapy, although abatacept has been shown to be similar in efficacy to TNF inhibitors in patients who are methotrexate-inadequate responders. Insurance typically dictates the use of a TNF inhibitor as first-line therapy. When a TNF inhibitor has been inadequately responsive, we have all the rest of the medications available, but we don't really know which is the ideal next medication to use, whether a non-TNF biologic or a JAK inhibitor is preferentially more likely to be effective.

There's currently a study ongoing funded by Patient-Centered Outcomes Research Institute (PCORI). Jasvinder Singh, who is now at Baylor Health in Texas, is the principal investigator. [The study] randomizes patients who have active disease or have been intolerant of TNF inhibitors to either a non-TNF biologic or JAK inhibitor to determine which might be a preferential next line of therapy. We don't know the answer yet.

Certainly, abatacept, tocilizumab, and rituximab or JAK inhibitors are next approaches in patients who failed TNF inhibitors. Rituximab seems to work best, or much better, in patients who are seropositive for rheumatoid factor and probably also for anti-cyclic citrullinated peptide (anti-CCP) antibodies rather than in seronegative individuals.

We also now have biosimilars available. The biosimilars are available to the TNF inhibitors, and now there are also biosimilars available to tocilizumab and to other medications which would not be used in the treatment of rheumatoid arthritis.

With tocilizumab, adalimumab, and infliximab biosimilars available, that adds another opportunity, based on reimbursement, for treatment of patients with rheumatoid arthritis. The treatment landscape has evolved dramatically over the past 40 years, mostly over the past 25 years, and has led to various options for treatment of patients with rheumatoid arthritis and sequencing of treatment.

Gallagher: Julie, from your perspective, what are you seeing from a practice management standpoint? How are payers shaping treatment decisions and formulary behavior? How do these policies affect the ability to initiate or continue care?

Baak: I am not clinical whatsoever. I just manage the practice. I have about 2300 patients and about 750 are on an infusion therapy. Our patients are medically complex; they have between 3 and 20 chronic diagnoses. I've been doing this job for about a decade. I would say in the last 2 years, we have found that the insurance companies—and I'm looking at the BUCAs: the Blues, the UnitedHealthcare, Anthem, Aetna, and Humana—are getting more and more strict on their formularies and what I call their “pay-to-play” list.

The biosimilars, from my desk, are not biosame. I had 2 patients in 2021 that were stable on a branded medicine. If a patient was willing to switch to a biosimilar at the time, back in those days, we were willing to do it, but both of those patients reacted so severely that we had to send them to the hospital.

We filed 2 med watch reports with the US Food and Drug Administration (FDA) on those, and they were both with UnitedHealthcare. We tried both of those patients back on the original biologic and they both failed. For one of them, it took 7 months to find another drug that she was successful with.

I see this differently in that the insurance companies, who are middlemen, are doing none of the actual work and making all of the money, and literally trying to practice medicine on my clinician's license. I think it's difficult. It's very difficult to be in health care. For the biosimilars, it's a race to the bottom if you're an independent practice. I don't infuse any AVSOLA or any Inflectra because the acquisition cost is higher than the reimbursement. I have single-case agreements with insurance companies for Trexima that I'm getting X amount of dollars per unit because, with what they contractually pay us for it, I would be writing a check. I wouldn't be able to keep my doors open.

So, I am very leery of biosimilars because if they're anything like what we've seen, it's a race to the bottom. On a positive note, these biologics have changed these patients' lives. They've given them their lives back. Patients that do well, do really well. It's a great tool to have in our toolbox, but I'm afraid of biosimilars based on how they've acted in the past.

Dr Kay: I'd like to jump in. While I agree with Julie that the reimbursement for biosimilars—especially for infusible biosimilars—has made it impractical, in many cases, to infuse the biosimilar because the reimbursement for the drug is lower than the acquisition cost for the drug, which makes no sense whatsoever for a practice that has to pay for the medication, I would disagree very much with the comment that the biosimilar is not equivalent in terms of efficacy or safety.

The 2 patients that had problems with the biosimilar, it's an unfortunate situation, but they might have had a similar problem if they had received the reference medication at that time. The biosimilars are not identical, so they're not the same, but they're highly similar without clinically meaningful differences. They've undergone extensive analytical studies, clinical studies, and have been reviewed and approved by the FDA. I've been involved in biosimilars since before they became available in the US and have written the chapter on biosimilars for 2 of the major rheumatology textbooks. The experience in Europe has certainly borne out that biosimilars are very acceptable, no less effective, and equally effective.

In Europe where there are single payers, national systems, where these medications are put out to bid, there's an economic advantage. I agree completely that the health care system in the United States—where you have pharmacy benefit managers (PBMs) that own the insurance companies and have health care delivery systems themselves—the decisions about reimbursement really are not fair, especially to independent private practices.

Biosimilars themselves have made effective therapies available to patients who otherwise would not have been able to receive these therapies because they've not only lowered the cost in countries which are not subject to the same kind of economic limitations that the United States health care system poses, but also have introduced competition in the market for biologics. The average sales price of branded Remicade has decreased significantly by over 50%, significantly over 50%, since the introduction of the first biosimilar infliximab, which was Inflectra. Now, with 3 biosimilar infliximabs, the cost has decreased drastically in the average sales price.

That's not necessarily the price that your practice is required to pay to acquire these, which is a system that really is unfortunate to say the least—and stronger words are indicated—because it makes it impossible for your provider to provide these therapies to the patients who need them.

Gallagher: Switching gears just a little bit to second-line and later therapies. After failure of methotrexate or a TNF inhibitor, many patients require advanced options with different mechanisms of action. Dr Kay, where does Actemra fit in the treatment appropriate for second-line patients? What distinguishes it from other agents in the space, whether from a mechanistic efficacy or safety perspective?

Dr Kay: As I mentioned before, usually insurance and pharmacy benefit managers require TNF inhibitor therapy as the first line of treatment, largely driven by economic reasons—the rebates and discounts that they get from the manufacturers of the TNF inhibitors. Most patients who are inadequately responsive to methotrexate are initiated on a TNF inhibitor.

When a patient is inadequately responsive to or unable to continue taking a TNF inhibitor, there are various options available, non-TNF biologics and JAK inhibitors. Tocilizumab, being an antibody against the interleukin-6 receptor, is one of these choices. In terms of post-marketing observational studies from registries, both in the United States and Europe, there has been no greater risk of adverse events and similar efficacy, essentially comparable efficacy to TNF inhibitors, when patients have been treated with tocilizumab compared to when patients have been treated with TNF inhibitors.

In terms of the efficacy, patients respond quite well when they're treated with tocilizumab. Not all patients respond to tocilizumab, but many do. It oftentimes is the next line after patients are inadequately responsive to a TNF inhibitor, but also abatacept is used in that situation. In seropositive individuals, rituximab may be used, but typically abatacept or tocilizumab are used more commonly.

However, JAK inhibitors, largely through financial incentives to PBMs, are being used more and more, especially with 1 manufacturer having a JAK inhibitor that is being marketed preferentially to pharmacy benefit managers with rebates and discounts that are attractive to the PBM.

Gallagher: Julie, how does access to Actemra compare with other second-line agents and are there administrative hurdles that impact its uptake or continuity?

Baak: There are administrative hurdles with everything. I would say that, from a practice management standpoint, where I sit, I have probably 45 patients on intravenous Actemra.

Our patients tend to be noncompliant on the subcutaneous version because they're now dealing with the administrative burden of working with the pharmacy benefit manager and setting up delivery. They don't have it in them to deal with OptumRx and all these other people.

The patients on infusion are more compliant because we have the administrative burden. The patients on subcutaneous tend to drift on and off. But I would say, in my patient population, Actemra is more of a third or fourth try medicine, from my desk.

Dr Kay: I have patients who are insured by Medicare and patients insured by other private payers. I have a number of patients on subcutaneous tocilizumab, and they're quite compliant. We have a specialty pharmacy through our institution with specialty pharmacy liaisons who call the patient monthly to schedule their refills. If the patient has to use OptumRx, these specialty liaisons still help them with navigating that morass.

If the patients are responding to the medication and are reasonably compliant, whether it be intravenous or subcutaneous, the patients who are on Medicare sometimes benefit from the fact that intravenous medications are reimbursed better by Medicare than the self-administered medications. Patients who are unable to afford subcutaneously administered biologics may be more able to receive an intravenous medication. Intravenous tocilizumab has a significant place in that part of the therapeutic armamentarium.

Gallagher: I want to continue on to a section that is top of mind for our First Report Managed Care audience: coverage, reimbursement, and patient access.

Julie, how do payer policies, such as step therapy or prior authorizations, impact your ability to prescribe and dispense advanced therapies like Actemra? Are you seeing any movement towards more flexible utilization strategies?

Baak: Everything that we do requires a prior authorization. I feel, as rheumatology offices, we have a giant target on our back because of the expensive medicines that are prescribed. This can change quarterly based on the formulary changes.

I think the most difficult situation for us is that when a patient is commercially insured with 1 plan, is stable on that drug, and then they switch at the beginning of the year. I'm actually dealing with PepsiCo on this—those patients were in a contract with UnitedHealthcare. PepsiCo has a white bag mandate for all infusible drugs. I was able to get a UnitedHealthcare person that I could email, and she would flip it to buy and bill on the medical side. Now, they switched on January 1st to Anthem, and my 5 PepsiCo patients have not gotten infused drugs.

It took me 6 months to get Anthem, get the right person at PepsiCo to get these patients switched to buy and bill. I've got 5 patients that have been off treatment for 6 months. Everything is difficult with prior authorizations and step therapies. To me, it seems like it's not about clinical efficacy; it's about what makes the insurance company the most money and who they can collect their rebates from, or pay to play, or whatever it is they're doing.

Rheumatology patients are only stable until they're not. However, I'm not interested in nonmedical switches and my clinical team isn't, and I have a whole arm of advocacy. We redact cases and put them on Twitter, and we have a TikTok channel that we bring patients on. If they want to advocate, we redact patient information. A lot of them just want to talk about it and that seems to get these cases overturned.

Gallagher: Dr Kay, how do these issues and payer practices affect clinical decision-making? Are patients experiencing delays? What are the consequences of those delays on disease progression and quality of life?

Dr Kay: Payer practices, which really refers to step therapy and the PBM formularies, certainly affect clinical decision-making.

The choice of medication is largely dictated by what the PBM will allow. Instead of making a clinical decision based upon evidence, one is choosing therapy based upon the likelihood that it will be reimbursed and allowed by the PBM, which is why a methotrexate-inadequate responder typically will get the TNF inhibitor that is most likely to be reimbursed by the PBM.

In terms of switching to other medications, sometimes the PBM has switched from the branded biologic to a biosimilar, and sometimes they're switching among biosimilars based upon better contracts that they receive. PBMs are middlemen who are making their money on the basis of discounts and rebates that they get from the manufacturer, not all of which they give back to the patient or the patient's insurance provider. The PBM is making a business decision about which medication they will reimburse, and that is the medication we have to prescribe.

Now, the PBM does not force me to prescribe the medication that is reimbursed. I can certainly prescribe something that's not reimbursed, but that's impractical for the patient. Patients are unable to afford paying for a medication that's not subsidized by their third-party payer. The cost of a single dose of branded adalimumab is about $3750 per dose. For a patient to spend $7500 a month on their medication, which is going to work out to about $80 000 a year, that's impossible for most patients.

Patients are willing or have no choice but to accept that medication, which is at least partially subsidized. Patients on Medicare are not able to receive copay forgiveness cards, so to speak. Patients who are on Medicare have an additional layer of barriers to being able to afford their medications.

When a patient has been on a medication and is doing well and the third-party payer changes their formulary and no longer reimburses that medication, there's certainly a delay based upon the time that it takes to write the new prescription, get that authorized, and that's something that the PBM recognizes and probably hopes for.

If a patient misses a dose of medication, that represents thousands of dollars of savings for the pharmacy benefit manager which contributes to their profits. The tactic of delaying while looking innocent as a process of requiring review and authorization is really contributing significantly to the profitability of the pharmacy benefit manager.

Disease progresses when not treated, and quality of life is reduced when disease is active. A patient who is not receiving adequate treatment is experiencing progression of their disease, progression of their structural damage, and decreased quality of life. Certainly, any delay in initiating effective therapy is going to impact quality of life and accelerate, or at least not slow, disease progression.

Gallagher: I want to conclude with real-world outcomes and the value of wraparound patient support. Dr Kay, what does the real-world evidence tell us about Actemra, especially in terms of durability, functional outcomes, and quality of life?

Dr Kay: The 5-year data from the AMBITION study shows that tocilizumab remains effective in many individuals over the course of the 5 years in the clinical trial.

Patients who are doing well are able to do well for a period of time and may not need to switch. Some patients lose efficacy and have to switch to a different mechanism of action, but patients who respond experience improvement in their physical function and improvement in their quality of life.

The real-world data that have been published out of registries, including the CorEvitas registry in the United States and multiple European registries, indicate that tocilizumab is equivalent to TNF inhibitors in terms of safety and efficacy with no increase in the risk of cardiovascular disease or other major adverse events.

Real-world evidence tells us that tocilizumab is an effective therapy for the treatment of rheumatoid arthritis—improving physical function, improving quality of life, and being well-tolerated in many patients.

Gallagher: Julie, how important are patient support programs in facilitating treatment initiation, adherence, and reducing administrative burden? Are these services influencing payer approval or helping practices sustain access?

Baak: I think the copay assistance cards for commercial patients are obviously keeping those patients on whatever therapy they're on. I think the Medicare Advantage patients are just in a bad spot, at least in my neck of the woods here, because those patients are basically super poor and they don't have the $2900 out of pocket, so they just have to go on triple oral therapy. They're not actually able to access the biologics, subcutaneous or intravenous, for the most part.

I would say that as far as initiation of treatment, the pharma-sponsored stuff is really important. I don't think it reduces my administrative burden whatsoever because I've got 23 support people for 4 clinicians. If we didn't have so many administrative burdens, we could help a lot more people. One of the things that's really been good for us is the patient appeal. I would like to see pharma pay for the patient appeal, because for the physician appeal, they consider me an independent, unimportant contractor. [They say,] "Oh, we didn't get the chart notes. We didn't do this," despite the fact that I have fax confirmations and chart uploads to ability in their portals. But if the patient files an appeal, now we have a contractual relationship between the patient and the insurance company. Now, all of a sudden, they get back to the patient. That's one of the things we've pivoted to about a year ago.

I'd like to see pharma sponsor that for their own drugs because the patients are having to come out of pocket to pay $50 for a patient appeal that looks like they've hired an army of lawyers, but it works. If it works, we do it.

Gallagher: Thank you both so much for sharing your insights today. Is there anything else you'd like our audience to take away from this discussion?

Dr Kay: I would just say that pharmacy benefit managers as middlemen add to the cost of health care, and they have incentives which are not necessarily aligned with those of the patients or the providers.

They are multibillion dollar organizations and Congress has recently started to look at pharmacy benefit managers and at the possibility of regulating pharmacy benefit managers. If the insurance company itself were to eliminate pharmacy benefit managers and directly manage its pharmacy without these middlemen, patients might be better off.

Baak: One hundred percent, yes. We need less middlemen, not more. Agreed.

Gallagher: Thank you both so much again. For our viewers, we hope this discussion helps inform value-based decision-making and improves understanding of the practical challenges and opportunities within the RA care continuum. Stay tuned to First Report Managed Care for more coverage on access reimbursement, and future of care delivery. Thank you for watching.

Baak: Thank you.

Dr Kay: Thanks for having us.