Julie Reed, MS, executive director of the Biosimilars Forum, weighed in on some of the biggest policy changes that could impact biosimilars, including the implementation of the reauthorization of the Biosimilars User Fee Amendment (BsUFA III) and the investigation into pharmacy benefit manager (PBM) practices.

What are some of the big biosimilar policy changes that the industry should be keeping an eye on and what actions can providers and administrators take to push them forward?

Absolutely. There's a couple key ones right now—and I sound like broken record so I apologize—but right now, the Senate Finance Committee and Congress are looking at PBM transparency. And I think that's a good start, but it doesn't go far enough, especially for biosimilars. We know what the problems are. We know that they're not providing competitive access to biosimilars. They're not preferring biosimilars. They're not supporting their uptake and lower cost. They're asking for high rebates, which the opposite of what we're trying to do. We don't want to add cost, we don't want to add rebates to a biosimilar. We want to give the lower list price and lower patients out-of-pocket [costs].

I think another key piece is—and we're excited about—is under the BsUFA III user fee negotiations. We will be working with the FDA to streamline development of biosimilars, which is a critically important. We're partnering with the FDA and bringing our collective experience with getting approvals across the world for biosimilars and the decades we've been doing this. There's ways we can create efficiency within biosimilar development. And I think that'll be key. If you can approve a biosimilar in less than 10 years, which we should be able to do, and if we can reduce the costs, that will have an impact on the outcome for patients' costs and what we can do for them, and so I think that's right. 

We will continue to work closely with CMS. The biosimilar special rule was part of the Inflation Reduction Act, and that is part of the the drug negotiation package that they're implementing. We continue to to work with CMS and that team so that will this special rule is implemented in an effective and positive manner for the long-term sustainability of the biosimilars industry. So, I think those are the 3 key things and, of course, will always be weighing in on patent reform and reducing barriers to bringing biosimilars to the US marketplace.

Videos

Julie Reed, MS, executive director of the Biosimilars Forum, takes a look at the 3 policy initiatives that could have the greatest ramifications for the US biosimilars industry.

The Top 3 Policy Initiatives That Could Impact the US Biosimilar Market

Hi, I’m Justina Petrullo for The Center for Biosimilars®, your resource for clinical, regulatory, business, and policy news in the rapidly changing world of biosimilars.

Here are the top 5 biosimilar articles for the week of July 17th, 2023.

Number 5: A review article shed light on the 

, including how these products are being priced, strategies companies are using to make their product stand out, and recommendations for policymakers to ensure the accessibility and affordability of these products.

 for its omalizumab biosimilar; Dongkook Pharmaceutical shared the launch of an insulin glargine biosimilar (Glargia); and Quebec, a province in Canada, said it’s adding a ranibizumab biosimilar (Byooviz) to its reimbursement list.

reintroduced the Biosimilar Red Tape Elimination Act

 to Congress. The bill aims to get rid of switching study requirements for companies looking to obtain an interchangeability designation for a biosimilar.

The US gained 2 more adalimumab biosimilars

 on the market: Fresenius Kabi's Idacio (adalimumab-aacf) and Biocon Biologic's Hulio (adalimumab-fkjp). The launches came after 5 launched over the Fourth of July weekend.

Number 1: The list price of Humira (reference adalimumab) had 

 over time that the list prices for new adalimumab biosimilars are now significantly higher than the original price of the originator, according to a report contextualizing net prices of adalimumab and the role of rebates.

To read all of these articles and more, visit 

Here are the top 5 biosimilar articles for the week of July 17, 2023.

The Top 5 Biosimilar Articles for the Week of July 17

 And with those great opportunities biosimilars provide, there are also challenges. Dr Kay, I don't want to come to you for just challenges, but I feel like I'd love to hear your perspective of some of the challenges that you've experienced as a provider related to biosimilars and inflammatory conditions.

: The biggest challenge is that the patient needs to share in the savings. A patient accepting a biosimilar, which is equivalent in effectiveness and comparable and safety is not giving up anything, they're gaining treatment with effective medication. But to make that change for the sake of saving the payer money, or the pharmacy benefit manager money, and not sharing in those cost savings, really doesn't make sense. So the success of biosimilars is dependent upon including the patient in the economic advantage of the biosimilars. In terms of challenges, a patient who's doing well on reference biologic medication, when faced with the suggestion of changing to a biosimilar, is going to ask why; [they might say] “I'm doing very well on the medication that I'm taking. What's in it for me?” In Europe, in countries where there's a strong social commitment, such as the Netherlands or Scandinavian countries, the individual patient follows the Enlightenment concept of the social contract and is willing to give up a little bit of something themselves for the good of society. So biosimilars have been very successful, especially in the Scandinavian countries, but also in European countries, such as the Netherlands, where there's a strong sense of social responsibility among the population. In the United States, it's a bit more complicated and patient education is critical. In the Netherlands, there was a study done in Nijmegen, where patients switched from reference infliximab to biosimilar infliximab and they found that although there was no change in disease activity over 6 months, 25% of patients discontinued the biosimilar after 6 months for reasons that were mostly subjective. The same groupconducted another study in which they switched patients from reference to etanercept to biosimilar etanercept and this time, they involve the pharmacists and nurses in the clinic to provide the patients with education. This was not a controlled study because patients were only provided with information about biosimilars. But patients who are educated about biosimilars had about an 8% to 10% discontinuation rate at 6 months, which compared to a historical cohort was within 2% of the historical cohort. So, first of all, there was a much lower discontinuation rate, and it was comparable to the discontinuation rate from patients who had previously been treated with reference products. So, education is incredibly important when initiating treatment with a biosimilar. And it's important to educate the patient initiating a reference product, but with a biosimilar to educate the patient that biosimilars have been studied extensively developed very carefully, and shown to be equivalent in efficacy and comparable in safety and immunogenicity with that education. If the other component of sharing in the financial savings benefits the patient, then we can be quite successful in using biosimilars in the United States.

: I agree with Dr Kay 100%. I think taking the time and spending it on education is imperative because I think especially with the injectable biosimilars, it's difficult for patients to be cruising on the reference product injectable, and then all of a sudden in 1month, get a new package with new packaging, a new form of administration, especially with adalimumab. Adalimumab reference product is citrate-free and patients really enjoy them because it doesn't cause burning or stinging when they inject. But some of the new adalimumab biosimilars might still have citrate, and patients might not be aware. They also may not be comfortable with the packaging. Do they have to pull it up into a syringe? Is it still an easily employed pen? I think taking that time upfront to understand what the patient’s perspective is on switching to a biosimilar, allay their concerns, and then understand even on a deeper level which biosimilar will they be prescribed, what that looks like, how can they use that, is really key to get them to buy into the idea of a biosimilar. And then you're right. The cost savings have to rally onto the patient because otherwise, you worry what's it all for?

: There's a big difference between the self-administered biosimilars and the infusible biosimilar. Infliximab is an infusible biosimilar. And the uptake of biosimilar infliximab initially when it was first released in 2017 was very low in the United States largely because it was not on the formulary in most institutions. But as institutions became more aware of biosimilars, and especially with 340B institutions, the savings became quite significant. Institutions started to use biosimilars and found them to be quite successful. For the patient sitting in an infusion chair, unless they read very carefully the writing on the bag, they're not going to notice that they're getting biosimilar infliximab compared to reference infliximab or even which biosimilar. And the experience that we've had is that when the biosimilar has changed to a different biosimilar there's been no increase in adverse effects. As you pointed out, the self-injectable biosimilars come in either a syringe or a pen and the autoinjectors are patented and proprietary to the manufacturer of the reference product. So each biosimilar comes up with its own autoinjector, which is visible to the patient. Some of these might actually be better than the reference product. And the reference product has a 3-step autoinjector, whereas a 2-step autoinjector just involves pushing it down on your skin, and everything else happens, you can't stop it. You just inject and then you hold it there and make sure that the injections have gone in completely for 10 seconds, and then you're done. So there are autoinjectors that are not cylindrical that are shaped with a flat surface on 1 side so they don't roll off the table. There are autoinjectors that have wider grips for patients with arthritis and compromised hand function. So the autoinjector is actually an opportunity for a competitive advantage over a biosimilar since the patient doesn't really feel the economic impact that much. And how do you differentiate yourself? You can't say that [they’re] more effective because a biosimilar cannot be more effective than the reference product. It can be a little bit safer. There's a biosimilar, etanercept, which has 3.7% injection site reactions in clinical trials compared to 17.2% with the reference product. The etanercept biosimilars won't be released in the United States until 2028, but there can be advantages as you pointed out. Reference adalimumab in the low concentration contains citrate and the high concentration does not contain citrate. And the citrate buffer contributes to the burning sensation. Some of the biosimilar adalimumab in the low concentration are citrate free, so that can be an advantage. The needle can be a smaller gauge. It can also be sharper. Some needles, patients reported, [are] somewhat dull and hurt a little bit more when they go in. So, there are plenty of opportunities for competitive advantages of biosimilars. But you also point out that education should be done by the provider, which is very important. When you have a patient with inflammatory bowel disease, comorbidities, compliance with medication, or activity of the disease, all of these things have to be included in a very brief, relatively brief appointment during which you don't have a lot of extra time to counsel the patient adequately about the differences between a biosimilar and a reference product. So the challenge to the provider is, how to educate the patient adequately about biosimilars while still addressing all of their medical needs.

 One thing to build off of that with provider challenges is also many large practices and health systems have their own integrated specialty pharmacies that they can utilize for patient education and coordination through the EMR [electronic medical records]. And one thing that's going to be really interesting is we have more biosimilars. We've already had this, but it's a biosimilar to be managed to the pharmacy benefit, so there's restrictive payer coverage. Only certain pharmacies can dispense. We actually ran a study that was published in the American Society of Health-System Pharmacy of the Emory Specialty Pharmacy [Atlanta, Georgia] that when we dispense internally, same provider, we had 22.5% better adherence when it was filled internally vs a PBM [pharmacy benefit managers]-owned specialty pharmacy. So that's another thing that we're definitely going to have to tug and pull on. How do we work with our payers if we're unable to fill internally as a provider to make sure that we've got good adherence data to have these patients be successful on the product.product?

: I couldn't agree with you more. At UMass Memorial Medical Center [Worcester, Massachusetts], we have our own internal specialty pharmacy. And we have pharmacy liaisons that help us with prior authorization and interface with the patients. They follow up with the patient. Pharmacists speak with the patient, address concerns, and enhance compliance. But the problem is that if a patient changes insurance, then they're no longer able to use our internal specialty pharmacy. Unless all pharmacies were created equal, there is a difference among pharmacies, and I would use this platform to advocate, payers, that you'd be more liberal in supporting specialty pharmacies and allowing institutional specialty pharmacies to dispense these medications because so much of the direct involvement of the pharmacy liaison with the patient and with the provider is important in compliance. And compliance with the payer is going to result less in the way of comorbidities and consequences of inadequately treated disease. So, there should be an increase in the number and use of institutional specialty pharmacies. But the problem is that the PBMs typically own their own specialty pharmacies. And the PBM is also on the payers. PBMs are becoming all-powerful and have many different aspects, which makes it difficult for the institutional control of specialty pharmacy distribution of drugs, which is actually optimal for the patient to be widely available.

This activity is supported by an educational grant from Boehringer Ingelheim.

Jonathan Kay, MD, discusses challenges that patients may experience related to biosimilars for inflammatory conditions.

Challenges Associated With Biosimilars

 Now let's discuss the role of biologics and biosimilars and disease management. What are the practical considerations for drug selection? Maybe Dr Kayal, we can start with you. And then Dr Chen, I'll probably want to pull you into this conversation as well. But first, Dr Kayal, what are some of the opportunities that biosimilars have for inflammatory conditions from a provider's perspective?

: Biosimilars are really an exciting addition in terms of the adalimumab biosimilars this year, at least in immune-mediated inflammatory diseases because the number one most important thing that they're allowing us to do is get more drugs into more patients hands; the fact that they are lower costs, and hopefully we're seeing that lower costs translate into patient lower costs as well. It's just making the treatment class the biologics more accessible for patients. And this is a big deal because although we have a lot of different health care plans and different insurance, formularies, and managed care plans, it still is across the board, it can be difficult to get the right drug into the right patient at the right time. The cost has always been a barrier for patients so the biggest thing that has been really wonderful about biosimilars, and this started of course, with infliximab, biosimilars, years ago, and now again more recently with the adalimumab biosimilars, is that we're able to get the drug to the patient at the time that they need. So we were talking a little bit about step therapy before and we're increasingly understanding this step therapy is not necessarily the right approach for many of our patients who are starting with severe disease that can only progress or increase in severity. And for these patients, you really need to start a biologic early on and you don't necessarily want to waste time going through the different step-up or step-lateral approach. You really just want to start the biologic upfront, and the cost was a big inhibitor of that, and now with the biosimilars at the lower cost they afford, we're able to start the right drug earlier for our patients and really prevent the disease severity progressing.

 Many times historically, it was given to the providers to understand the value of a biosimilar but obviously, our providers have really caught on. And they understand the value that plays in treatment. And they understand that it can reduce the cost for the patient if the plan has it that way. So maybe we pivot from the provider perspective to a payer. As a payer, Dr Chen, what are your thoughts on biosimilars? And how are they really changing the landscape and some of these high costs disease states?

: As we have discussed earlier, the development of biosimilar drugs is much lower in cost in comparison to biologics, as well as the medication itself. It is much lower overall, in the cost itself, but also, ideally, it is used interchangeably where we are able to switch somebody already on a biologic to the biosimilar, which, could give us even more saving in the long run.It will increase our market competitiveness and overall create more innovations as well as, hopefully, cost saving in the long run.

 I’m hopeful that cost savings not only save for the employer group because I think that’s so important as they continue to cover newer innovative treatments, but for the payers also. Hopefully, that passes on to the patients as well because ultimately, we want them to be able to afford and have access to these medications.

Maia Kayal, MD, MS, and Kimberly C. Chen DO, MSHLM, discuss opportunities that biosimilars provide for inflammatory conditions from both a payer and provider perspective.

Opportunities Provided By Biosimilars

: Speaking of biosimilars, one of the things we haven't defined for our viewing audience is what a biosimilar is. Dr Kay, maybe you can speak to what is the biosimilar and maybe discuss the potential impacts of a lower cost compared to the reference product.

: Certainly, a biosimilar is a copy of a biopharmaceutical, which no longer is limited by patent. And that copy is an exact copy of the amino acid sequence but because these are produced in living cells, it can't be a completely exact copy. So there's slight variation in terms of post-translational modifications such as constellation, however, the definition in the biologics price competition and Innovation Act of 2009 is the biosimilar is highly similar to the reference product without clinically meaningful differences. It's expected to have similar quality, purity, and potency to the reference product and in practical terms, is studied in terms of analytical comparisons with the reference product, then shown to be highly similar without clinically meaningful differences. There's then a pharmacokinetic study that shows equivalent pharmacokinetic parameters, and at least 1 clinical trial and a disease for which the reference product is approved to show equivalent efficacy throughout the development process immunogenicity is assessed and the biosimilar is shown to be no more immunogenic than the reference product and also comparable in terms of safety. So essentially, a biosimilar is a copy of a biopharmaceutical, it's not a generic because generics are small molecules, where the active ingredient can be reproduced exactly. But the biosimilar, being a complex protein, is not an exact copy. But is shown in an extensive development process to be equivalent in its efficacy, and comparable in its safety to the reference product.

 Excellent overview. Thank you for going through that with us. So now that we've defined biosimilars maybe Dr Chen, what is the potential for these biosimilars to lower costs compared to this reference product?

: Now there is definitely a lot of opportunity in just talking about the development. On average, new medication will take minimally greater than 10 years and the development costs over $2.6 billion. But biosimilars actually take approximately 5 to 9 years and are only about $100 million. So you can even see the cost comparison on developing the drug itself. In 2020, the research actually showed that biosimilars have saved nearly a billion dollars and in 2022 they have actually projected a savings of over $30 billion. And if we continue the use of biosimilars, there's a potential savings of $183 billion in the next 5 years.

 It sounds like there's a great opportunity for biosimilars leveraging almost like our partners have in Europe to really decrease the cost of care and still provide high value.

Jonathan Kay, MD, and Kimberly C. Chen DO, MSHLM, define what a biosimilar is and discuss the potential for a lower cost than the reference product.

Savings Potential With Biosimilars

 As we know and has been pointed out, there's going to be barriers to treatment. Dr Kay, [as] someone who does a great job treating patients, and another expert in the field, I'd love to get your thoughts. With all these biologics available, it's really tempting to say we've got plenty, but we know that there are still barriers that are preventing patients from being on therapy long term. Could you discuss some of the barriers related to the access of biologics maybe from an economic and even health disparities perspective?

: Certainly the economic barriers are there because these medications are quite expensive. They're not necessarily expensive to the patient because the patient pays, in most cases a copayment that's relatively negligible compared to the cost of the medication for patients who have Medicare insurance and Medicare Part D; they're paying 20% of the cost of the medication up to the doughnut hole, and then the medication is covered fully. But the real barrier based on economics is an almost artificial barrier that's placed by pharmacy benefit managers because pharmacy benefit managers are companies that contract with payers to manage their formularies and they get paid an administrative fee based upon the list price of the medication. They also get discounts and postdoc rebates from the manufacturer so that the amount that they pay for the medication is much less than the list price. They share most of that rebate and discount with the payer. But they don't necessarily disclose the complete amount so that their profit is generated both by the administrative fees that they gain from the small proportion of the list price, and also that proportion of the rebates or discounts that they keep. So the economic barriers are generated by the pharmacy benefit managers tiers the formulary, essentially the way many of us who fly airlines choose to fly a specific airline or group of airlines so that we can get status on that airline and a greater likelihood of upgrades or something like that. The pharmacy benefit managers are aligning the incentives so that they can have the most patients on the medication that will give them the largest rebate from the manufacturer. The more patients they have on a given medication, the larger the rebate usually is from the manufacturer. So the pharmacy benefit managers require prior authorization, not because they're trying to help us determine the most appropriate medication for a patient, but rather because they're trying to align the medication that's prescribed for the patient with the medication that will give them the best advantage in negotiating discounts and rebates. So the economics are complicated; medications are expensive. They're expensive to someone, certainly to society, but not necessarily directly to the patient. But the cost of the medication and the opportunities for pharmacy benefit managers to gain rebates and generate profits limits access to some biologics because the providers’ choice is not completely free and is dictated by the pharmacy benefit managers’ formulary. There are certainly health inequities where disadvantaged groups don't have the same access to health care that everybody else does. And with limited access to health care, these medications are perhaps the least accessible since they're expensive and almost impossible to obtain without some sort of coverage assistance. Medicaid provides assistance so that those disadvantaged groups that are covered by Medicaid are able to have access to these medications, but for the uninsured, whether they're uninsured because they're financially limited or whether they're uninsured because they are not working in the employment sector—they may be retired and can't afford the coverage for prescriptions—those individuals are compromised in terms of their access to these very effective medications. So their health care disparities are not necessarily aligned with social inequities but are more economic difficulties. Retired individuals oftentimes have to go to work, bagging groceries at a local grocery store to get health insurance. [I have] not seen that at Starbucks, where baristas are retirement age, but I wouldn't be surprised if we start seeing that as well.

 I'm probably more of an economy guy myself, relating to your thing, but I definitely recognize what you're saying. It is a very tricky environment because you do have pharmacy benefit managers that are managing the benefit and also sharing some of the rebaiting. You also have health plans and employer groups that are trying to afford the increasing cost of care related to both medical and pharmacy benefit while pharmacy benefit managers may just see that pharmacy piece of it. There might be true medical cost offsets if you gave a patient therapy sooner. The more and more we aligned the benefits between pharmacy and medical, I think it's going to create better access and I think you really describe that well. And I do want to hit on health inequities because one thing that’s so important as providers and payers is that we come together to make sure that patients have an equitable chance at receiving a positive health outcome. And if they have transfer patient vulnerability and can't receive a biosimilar infusion, then how do we make sure we have something they can take in the comfort of their home? Because we know based on patient zip codes we can live 6 miles away or 300 miles away and they still have that same transportation vulnerability, and being able to attack that financial toxicity, transportation vulnerability, and make sure that we have equitable care, continues to be a challenge and something we have to work through even with extremely efficacious treatments.

: Transportation vulnerability isn't limited to being unable to attend an infusion center to get an infusible biologic. Transportation vulnerability oftentimes limits access to medical appointments, and limiting access to medical appointments often delays or even prevents treatment of active disease.

:I agree with that. I think along those lines, it's also about where patients work and whether their employer is even willing to give them time off to get the infusion, make it to that appointment, where they learn how to use an injectable. A lot of what we provide at our center is not only, of course the medical care and the medical support, [but also] the psychosocial support, because that's where, increasingly again, understanding that the psychological impact of this disease can be devastating. But if a patient doesn't have time to take off from work, to come and see you in the office, or even see their therapist that day, then it's just going to be a continuous downward spiral of the impact of the disease on their day-to-day.

: One thing I do want to note with all health plans, especially high-cost patients, usually they have a case manager within the health plan that can help support them in getting some of the social determinants of health issues, such as transportation, health plan, sometimes with an issue with the Medicaid sector, and sometimes with a commercial or self-funded group, it can make exceptions to pay for some of those care needs. So always keep in mind that collaboration between the health plan and providers is really a win-win to better support our patients, especially the ones with SDOH [Social Determinants of Health] needs.

Jonathan Kay, MD, reviews the barriers related to access to biologics such as economic barriers, health inequities, or disparities.

Barriers to Biologics Access

 As we think more specifically about these inflammatory diseases, we know there’s a lot of medication classes, from anti-TNFs [tumor necrosis factor] to IL-17s, IL-23s, to JAK [Janus kinase] inhibitors. Dr Kayal, you’re really an expert in this space. Could you provide an overview of the biologic use in inflammatory diseases? Maybe focus on one of the upcoming biosimilars [for] adalimumab because I know we’re all awaiting that as well.

: That’s a great question, and I’m so excited because I think now more than ever, we have a lot of great therapeutic options that we didn’t even have a couple of years ago. It’s a great time to practice in this field because we do have some great options.

As you said, we have the anti-TNF agents. These include infliximab, adalimumab, and certolizumab. We have the anti–[IL-]12/23 agent, which is ustekinumab. More recently, we’ve had the approval of the anti–IL-23 agent, which is risankizumab. We have anti-integrin therapies in inflammatory bowel disease specifically, which include vedolizumab, and it’s something that we use quite frequently for our patients with colitis and [Crohn] disease. In the last couple of years, we’ve seen the rise of small molecules like JAK inhibitors, starting with tofacitinib, which is a pan-selective JAK inhibitor, and most recently, upadacitinib, which is a JAK-1 selective agent.

It's interesting because I get the question asked a lot: Which drug for which patient at which time? The answer is there’s no one-size-fits-all. Choosing the therapy is really dependent on the patient and their risk factors, but even more importantly, we think a lot about…disease severity and…disease acuity and essentially how sick are they right now and what is the potential for them to get sicker over the long term? We think about their present illness, and then we think about their risk of progression [vs] their chronic illness essentially. Using those tidbits, you start to develop a therapeutic plan for your patient.

What’s really interesting and exciting is that, as you mentioned,…just this year alone we’ve seen the approval of multiple adalimumab biosimilars, which is really exciting because what we hope these biosimilars will…make it easier for us to treat our patients and get more drugs into patient hands in a more efficient and cost-effective way.

 You did a great job talking about the continuum of care because we’re not just looking at these disease states in a one-time treatment or if it’s a one-time cycle. A lot of times, we’re looking at control over that time period, and patients through their progression of disease may go through different classes that you really outlined.

Maia Kayal, MD, MS, provides an overview of the biologics used in inflammatory diseases.

Biologics Used in Inflammatory Diseases

 One thing you talked about was what’s driving the expense, and the great thing is we have new therapeutics that are providing really good resolution of disease, limiting the type of progression that we’re used to with patients and as Dr Kay mentioned, living productive lives.

Now the main thing we’re working on is how we control those comorbidities that lead to nonadherence or may lead to exacerbation of current symptoms and also making sure that we have the right coverage—so dealing with financial toxicity, transportation vulnerability, and having a great proportion of days covered. Even with that, we know there continue to be drivers, and a lot of times those drivers exist within the pharmacy in terms of acquisition cost, but also as you talked about Dr Chen, the medical benefit and some of those medical costs.

Dr Chen, I’ll turn to you once more. What are some of the key drivers contributing to the economic impact of inflammatory diseases as a whole within the US?

: One thing we have learned because of the add-ins of new pharmaceutical drugs is that specialty drugs have come into play as one of the key cost drivers and also unplanned care, even though our surgical has gone down just because of these specialty drugs. I do want to also point out [that] the treatment for the chronic inflammatory condition has actually nearly doubled in the past 20 years. So even though the surgical costs have gone down, pharmaceutical spending continues to increase and has become one of the highest costs for almost all the health plans as well as health care providers.

: The acquisition costs of the medication are most important because surgery down the road may be covered by different insurance. Patients typically switch insurance coverage every several years, and the insurance provider that is covering the cost of the expensive medication may not be held responsible for the cost of surgery down the road. So the cost to the insurance provider of current medications may not mitigate savings in the future, which is an important consideration to the payers because their expenses may not be balanced by savings.

: I think that’s a great point, and something that I always think is so fascinating, at least for inflammatory bowel disease, is we thought that as we had these biologics being approved and a lot more guidelines were incorporating them that we would see reduced surgery rates, for example, or we would see reduced extraintestinal manifestations and reduced disability.

In the United States, there is still a big delay to start [our patients on] these medications…, so there’s a long lead-up to start the biologic. And during that time, the patient might be inappropriately managed with medications that are not therapeutic enough for them or optimized enough for them, and that’s the curative time [during which] they’re most vulnerable. The window of opportunity to start a good drug is not happening, so they’re getting surgery, and the costs are high in that up-front phase, and they still need to go on a biologic [postoperatively].

At least in the United States, unfortunately, the community hasn’t necessarily adopted the early use of biologics, which is really important. So the costs haven’t necessarily been driven down.

: You point out a very interesting dichotomy between gastrointestinal disease and rheumatologic disease [because] in gastrointestinal disease, inflammatory disease, surgery is the initial treatment for active disease, whereas in rheumatologic disease, the surgery is usually a result—or treats the results—of chronically active disease later on.

: I think it’s the same. It’s just that we do think it’s a chronic progressive disease similar to rheumatoid arthritis and other rheum conditions, but we do have this window of opportunity if we start the drug at the right time. If it’s early, you can prevent that progression, and the surgeries that we typically perform in inflammatory bowel disease are either resection for obstruction or resection for very active colonic disease, so a colectomy. Both of these conditions can be prevented if the right drug is started at the right time.

Sometimes by the time a patient is going to surgery, they’ve had years of chronic progressive disease that has been inappropriately managed, not optimized, no outcomes being met, and the ultimate result is surgery. By the time they see some of us, the disease has smoldered for so long that you haven’t had a chance to make an impact, so surgery becomes the only option. You do want to protect against that progression again, and you want to kind of do some postoperative prophylaxis, and that’s where the biologic [postoperatively] comes into play.

: One thing I do want to add is we talked about the driver the specialty drugs is one biologic but the other things that unplanned care- while we talk about the surgery because surgery could be planned or unplanned but those unplanned as you said, obstruction, the patient coming in for emergency care as well as readmission because many of these patients have multiple readmissions. These unplanned in-patient visits and multiple readmissions are where it really drives up their medical cost as well.

 You all brought up some great points, from readmissions to therapeutic cost to delaying surgery and also the impact that has. If it’s a 3-year benefit and we have high turnover in a plan, you might not see the benefit or the return on investment to that patient that you’ve paid for. These are all really great comments.

One thing that really resonated with me, though, was starting the right therapy for the right patient at the right time. We utilize step therapies, stepping through different frontline treatments that may not always be best, but they might be in terms of a treatment pathway. One of the things we’re seeing in psoriasis and other diseases is certain patients with certain risk factors might need a higher-cost therapy up front. They don’t end up saving on the cost over time based on the cycling through different therapies and the avoidance of those loading doses that really cost a lot to the plan. I really like how you teased that out.

A panel of experts review the key drivers contributing to the economic impact of inflammatory diseases in the United States.

Cost Drivers Contributing to the Economic Impact of Inflammatory Diseases

 When we think about these diseases, we really need to focus on the humanistic burden. Dr Chen, I’d love to get your thoughts as we kick this off. What are some of the humanistic and economic impacts that affect patients with inflammatory diseases? That can range from their quality of life and presenteeism at work to direct medical expenses like ED [emergency department] visits and hospitalizations and even indirect costs such as health care resource utilization. I’d love to hear your perspective on that as a payer.

: Exactly as you said—patients with rheumatoid disease are impacted significantly in their quality of life because of the pain, the medical treatment, surgeries they go through, and also impaired function. [That] not only [affects] them, but also [affects] their family and their coworkers as well when we talk about direct and indirect economic impacts.

We all know they have such a high health care cost that’s due to…the specialty drugs…as well as surgery and in-patient care. Those are the direct costs…,but some of the indirect costs that you have mentioned [are] a decrease in productivity at work, their coworkers significantly having to help them, as well as earlier disability and disability payment. Also, transportation, medication cost, and the costs for individuals with inflammatory disease can just go on and on, and to your point earlier, the mental health impact is not even being explored.

 Absolutely, I don’t know if any of our colleagues have any more to add. One thing that really stands out to me is as you mentioned, there are other indirect costs in terms of caregiver burden, but also that this disease is something these patients will live with. Our goal is for them to live a highly productive life, but when you have health care resource utilization and have to travel and have transportation vulnerability, [that] can really impact the patient as a whole.

: I agree, and I think along those lines, exactly as you said Dr Chen. You mentioned disability, and we’re increasingly recognizing that disability is a major comorbidity for these patients, both related to the disease manifestations itself but then also to the stress of the disease and its impact on their day-to-day life.

Something that we’ve been adopting in gastroenterology is actually disability- related quality of life and using that as an outcome for our patients because it’s a big deal for patients to not be able to get through the day, not be able to go to work or manage their personal life. I think we increasingly understand how…immune-mediated inflammatory diseases are impacting disability. We’re recognizing that it’s an outcome that we need to improve upon for their lives.

: On a more positive note, in rheumatologic diseases, disability used to be an inevitable consequence of the disease [despite] the treatments that we had, but over the past 25 years with biologics available, disability has been markedly decreased. Patients with rheumatologic diseases can now look forward to normal life and normal function and not necessarily anticipate surgical procedures. It used to be when I started in rheumatology that patients would anticipate having both hips and both knees replaced, surgery on their hands, and nowadays a patient with rheumatoid arthritis treated aggressively can expect to have a normal life managed with once-weekly or biweekly medication.

: That’s amazing. Just that progress alone is wonderful.

: One thing I do think is important to note is the overall cost for these patients. I think a lot of times we focus on the medical expense, but commercial patients tend to be very young because most of our inflammatory [diseases] tend to onset at a younger age. It’s important for us to incorporate those indirect costs like the disability that you guys talk about because many commercial payers are self-funded. And if we just look at it as we compare it with Medicaid or Medicare, I think we’re not…looking at what the commercial payers are paying for that.

Experts discuss the humanistic and economic impacts that affect patients with inflammatory diseases.

Humanistic and Economic Impact of Inflammatory Diseases

® stakeholder summit program titled “Interchangeable Biosimilars in Inflammatory Diseases.” I am Dr Ryan Haumschild, director of pharmacy services at Emory Healthcare and the Winship Cancer Institute in Atlanta, Georgia.

Joining me today in this discussion are my colleagues, Dr Jonathan Kay, the Timothy S. and Elaine L. Peterson Chair in Rheumatology; professor of medicine and [of] population and quantitative health sciences, director of clinical research in rheumatology, and the executive codirector of the MD-PhD program at UMass Chan Medical School, UMass Memorial Medical Center [in Worcester, Massachusetts].

Dr Maia Kayal, assistant professor [at the] The Susan and Leonard Feinstein IBD [Inflammatory Bowel Disease] Center [and in the] Dr Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai [in New York, New York].

Dr Kimberly Chen, senior health plan executive, expertise in Medicare, dual Medicaid commercial market.

Today our panel of experts will provide an overview of the clinical, economic, and humanistic burden of inflammatory conditions in the US, discuss the role of biologics and biosimilars in disease management and practical considerations for drug selection, define interchangeable biosimilars, and finally discuss the potential value of these agents to patients, payers, and providers in the treatment of inflammatory diseases. Thank you and let’s begin.

As we start this discussion today, I think it’d be really important to provide an overview of the clinical, economic, and humanistic burden of inflammatory conditions in the United States. Dr Kayal, could you give an overview of the clinical manifestation of these inflammatory diseases, focusing on the prevalence, some of the clinical impact, and even risk factors that we should be considering?

: Of course, thank you for the question. We know that immune- mediated inflammatory diseases have a prevalence of about 5% to 7% in the United States. The type of immune-mediated inflammatory diseases can be grouped based on the primary system that’s involved.

So in gastroenterology, which is, of course, my specialty and the area that I know the most about, we can group them according to inflammatory bowel diseases. This includes [Crohn] disease and ulcerative colitis. In rheumatology, Dr Kay’s specialty, of course, we have spondyloarthropathies, and these include ankylosing spondylitis, psoriatic arthritis, and then in addition to [those], rheumatoid arthritis. There are also immune-mediated inflammatory diseases in dermatology. These are psoriasis and hidradenitis suppurativa. Of course, the clinical manifestations vary for all of these diseases according to the systems that are involved. There’s no 

 risk factor for all of these diseases, of course, because they are across a wide spectrum of organ systems.

We do think that there might be a genetic predisposition to many of these conditions. Across the board, we think that tobacco use might be associated as a risk factor with some of these conditions, obesity, and age, but truly we haven’t figured out the precise risk factors for all of them. Again, we do know that perhaps in more cases than not, there is a genetic predisposition.

 That was an excellent overview, and obviously there’s a lot to consider. When we think about that, there’s also the consideration of comorbid diseases. We know that these comorbid diseases are on the rise, causing considerations for payers and providers, and uniquely there’s becoming more literature around metabolic disease and other things that we’ve really got to think about when we’re treating the patient as a whole. Dr Kay, maybe I can transition to you. What are some of the comorbid conditions that are typically seen in patients with inflammatory disease?

: Inflammatory diseases tend to increase the risk for cardiovascular disease. Atherosclerosis accelerates with chronic inflammation and malignancies. Lymphoma is also increased in its incidence in patients with inflammatory diseases, typically with more active inflammation.

For example, in rheumatoid arthritis, with the most active rheumatoid arthritis, the risk of lymphoma is markedly increased; however, with control of the disease and those comorbid conditions, the risk is decreased. In rheumatoid arthritis, interstitial lung disease is a major comorbidity that occurs in about 7% of patients with rheumatoid arthritis. Again, [it’s] treated the same way as rheumatoid arthritis, with anti-inflammatory therapy.

There are also comorbidities such as depression, which can occur as a reactive depression. We’re not really sure as to what the pathophysiology of depression associated with inflammatory diseases might be. We just presented a study at the European Alliance of Associations for Rheumatologymeeting that showed that there’s a 1.2-fold increased hazard ratio of postpartum depression among women with inflammatory arthritis compared to women without rheumatic disease. The risk of depression is increased in patients with inflammatory disease.

So atherosclerotic cardiovascular disease, lymphoma, interstitial lung disease, depression, and then of course the comorbid conditions that are associated with heart diseases, such as spondylarthritis, [which] is associated with inflammatory bowel disease or with uveitis or psoriasis. There [are] a number of comorbid conditions, most of them are shared pathophysiology and shared risk, but some of them are a result of chronic inflammation.

 Based on that response, there’s a lot to consider. I think one of the things you really highlight is the importance of mental health. We know with these patients, a lot of them are going to be on more chronic treatment, and if we want them to be successful, sometimes you got to really improve some of those underlying comorbid diseases to have a good proportion of days covered, adherence so a patient can really have better resolution of disease and better control.

Hopefully, that’s something that we can discuss more today because I feel like not only is it choosing the right treatment, it’s maintaining the right motivation and really focusing on all aspects of that patient as you so eloquently pointed out.

Maia Kayal, MD, MS, and Jonathan Kay, MD, provide a clinical overview of inflammatory diseases and describe comorbid conditions typically seen in patients.