It makes intuitive sense: Setting a specific goal and working quickly and systematically toward it should bring better results than slowly floundering toward an amorphous endpoint.

That’s the basic idea behind treat-to-target (TTT) strategies in rheumatoid arthritis, and since 2010, data seem to support it: Rheumatologists who pick a therapeutic goal and a related disease activity measure and work in partnership with cooperative patients to achieve it, get better clinical responses.

So important has this concept become that it’s now being tied to reimbursement. Rheumatologists who submit proof that they record disease activity measures in their patients will get points toward fulfilling quality reporting requirements for the Merit-Based Incentive Payment System (MIPS) option in the Quality Payment Program established by the Medicare Access and CHIP Reauthorization Act of 2015. Those points go toward achieving a bonus in Medicare reimbursement; those who can’t show it will edge toward a financial ding.

But despite the twin carrots of better patient outcomes and bonus payments from the Centers for Medicare & Medicaid Services and the stick of a 4%-9% Medicare payment penalty during the years 2019-2022 (and 9% thereafter) for quality outcome measures reported in 2017 and beyond, studies show that up to 60% of U.S. rheumatologists don’t regularly incorporate TTT strategies into how they treat their RA patients.

“It’s not an easy question, and there’s not a single answer,” said Jeffrey Curtis, MD , the William J. Koopman Professor of Rheumatology and Immunology at the University of Alabama, Birmingham.

“There are patient reasons. There are doctor reasons. And there are extrinsic reasons. But I would say the number one reason it’s had limited adoption is that it simply hasn’t been made easy enough.”

The ABCs of TTT

In 2010, Austrian rheumatologist Josef Smolen, MD , leading an international task force, proposed 10 recommendations for improving the care of patients with RA. These were based on the concept that choosing a therapeutic target – low disease activity or remission – and aggressively pursuing it with frequent medication changes accompanied by frequent disease activity measurements would result in improved short- and long-term outcomes.

Disease activity measures (DAMs) were crucial to the concept. In order to treat to a target, one must not only choose a target but also have a validated means to regularly measure progress. The task force didn’t say which DAM would be most appropriate, and research since then suggests that the tool used to measure progress doesn’t matter nearly as much as the target itself.

Shared decision making is also a core tenet of the technique. Physicians work with patients to identify the best treatment target for each individual and decide together how to reach it.

It is not a new concept, Dr. Smolen and his colleagues explained in their landmark paper ( Ann Rheum Dis. 2010 Apr;69[4]:631-7). “In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In the care of patients with diabetes, hyperlipidemia, and hypertension, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA1c [hemoglobin A1c] levels, check blood pressure, and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”

Yet rheumatologists had not adopted a similar paradigm, despite the surge in availability of effective disease-modifying antirheumatic drugs (DMARDs). Although clinical studies of these new drugs clearly showed that remission was possible for many patients and that achieving remission quickly could prevent irreversible joint damage, few patients were getting those drugs even if they had long-standing disease.

The task force suggested setting a treatment aim of remission or low disease activity, seeing patients every 1-3 months, and switching therapy as often as necessary to reach that goal. Tracking improvement required consistent measurements and recording of a DAM. The recommendations, which were updated in 2014, didn’t specify a certain DAM, saying that the patient’s individual clinical picture should guide that choice ( Ann Rheum Dis. 2016 Jan;75[1]:3-15 ). Shared decision making between the patient and rheumatologist was at the foundation of this concept.

Fast-forward to 2015. As TTT was increasingly embraced in Europe, data began to emerge supporting its clinical validity. A study presented at the American College of Rheumatology (ACR) annual meeting in San Francisco that year showed that treating RA patients toward a target of remission or low disease activity worked immediately and resulted in higher remission rates.

Sofia Ramiro, MD, of Leiden (Netherlands) University Medical Center found that employing a TTT strategy increased the likelihood that a patient would achieve remission by 52%. She also found that TTT strategies lowered disease activity and even improved remission rates for patients who had never received DMARDs.

But in 2017, a meta-analysisfound conflicting results among the 16 published randomized, controlled trials comparing TTT against usual care (Health Technol Assess 2017. doi: 10.3310/hta21710 ). The authors concluded that TTT was more effective for newly diagnosed patients, in whom it increased the chance of remission by about 50%. For those with longstanding disease, TTT was not significantly different from usual care.

Despite limited, and somewhat contradictory, clinical evidence, TTT is becoming increasingly accepted, especially in Europe. In 2016, the European League Against Rheumatism updated its recommendations for RA management (Ann Rheum Dis. 2017 Jun;76[6]:960-77). The document contained a recommendation to use low disease activity or sustained remission as the treatment target for every patient, to monitor disease activity with a validated measure every 1-3 months, and to change therapy as often as every 3 months in the case of no improvement or by 6 months if the target hasn’t been reached.

In its most recent 2015 RA treatment guidelines, the ACR also endorsed the strategy, though somewhat obliquely, and did not require rheumatologists to conform to it ( Arthritis Care Res. 2016 Jan;68[1]:1-25 ).

The concept of TTT, if not the explicit demand to practice it, now appears in the list of quality indicators rheumatologists can choose from in order to fulfill quality performance reporting requirements in Merit-Based Incentive Payment System. Periodic assessment of disease activity in RA patients with a validated DAM is one of the acceptable quality measures for rheumatology. It’s not designated as a high-priority measure, but there it is, item No. 177, tying clinicians at least indirectly to a TTT approach for their Medicare patients: The percentage of patients aged 18 years and older with a diagnosis of RA who have an assessment and classification of disease activity within 12 months.

Slow on the uptake

Despite the data and the dictum, however, TTT remains an outlier in the United States. The most recent studies suggest that most U.S. rheumatologists do not employ it.

Dr. Curtis is the primary author on one of the newest studies, which employed a 26-question survey about the use of a quantitative measurement in RA patients and attitudes about using it ( J Rheumatol. 2018 Jan;45[1]:40-4 ). The survey went out to almost 2,000 rheumatologists; 439 returned it.

Overall, just 44% said they “always practice in a treat-to-target manner, regularly using a scoring metric.” Younger physicians, those in group practices, and those who made regular use of TNF inhibitors were more likely to practice this way. A total of 35% said they never used a quantitative metric for their RA patients.

“The No. 1 reason given about not using them is that it’s too time-consuming and not easy enough,” Dr. Curtis said in an interview. “Logistics is a key barrier.” Busy clinicians don’t want to spend time entering data into an electronic medical record, and there aren’t easy ways to merge a specific DAM with a practice’s chosen EHR. “There’s a hassle factor, for sure.”

The age gap was interesting but not unexpected, he said. “Older rheumatologists say they like to go by their gut, by a clinical gestalt,” Dr. Curtis said, while younger physicians without decades of experience are more comfortable with such clinical tools. For some, age contributes to a kind of clinical inertia. “Doctors trained in an earlier era might be more tolerant of patients not doing as well. I’m a younger physician, and I have never known the era of not having biologics. They lived and practiced in that era, so their spectrum of what’s ‘normal’ and acceptable for patient progress may be wider.”

The research of Daniel H. Solomon, MD , of Brigham and Women’s University, Boston, tells a similar story.

He and his colleagues investigated whether a 9-month group-based learning collaborative could improve TTT numbers among 46 rheumatologists at 11 practices. The endpoint was a combination of four TTT principles: recording a disease target, recording a disease activity measure, engaging in shared decision-making, and changing treatment if disease target hasn’t been reached.

At baseline, 64% of visits to these rheumatologists had none of the TTT components present, 33% had one component, and 2.3% had two components; just 3% of the visits included all of the components (Arthritis Care Res. 2017 Aug 22. doi: 10.1002/acr.23343 ).

The project consisted of nine sessions, most conducted by webinar. The entire practice team took part, learning the principles and practices of TTT, identifying their unique barriers to implementing it, and coming up with their unique way of integrating TTT into their practice. It was fairly successful, Dr. Solomon said in an interview. After the intervention, 57% of the exposed practices had incorporated TTT.

In January, Dr. Solomon published a follow-up study of the stability of those changes (Arthritis Care Res. 2018 Jan 5. doi: 10.1002/acr.23508 ). He was impressed with the results. Most sites from the first cohort had sustained the improvement during the second training period (52%).

“We found that people could implement it effectively when we gave them the tools to do it,” he said. “It’s definitely achievable, but it takes some commitment and guidance, and the realization that everyone can contribute to success in a collaborative manner.”

Technology, or the lack of it

Many rheumatologists view TTT and the consistent measuring it involves as just one more headache-inducing time suck, said John Cush, MD .

Dr. Cush, director of clinical rheumatology at Baylor Scott & White Research Institute, Dallas, does employ TTT strategies. “I believe TTT makes you a smarter doctor and gives your patient the best chances of improvement. It pushes both of us out of complacency when we’re tempted to go with the devil we know. Yes, change is a radical thing, but in RA change is almost always good. I think until people are forced to do that, they won’t realize the benefit.”

But at the same time, he freely admits that the time spent ticking boxes on a paper form or a computer, and being forced to report those to a federal agency, could be the camel-breaking straw for many.

“It’s going down the path of what makes medicine sucky,” he said in an interview. “Bean counters telling me how to practice medicine, who think they can use this TTT to manage what I do. I don’t need more people trying to regulate my life.”

Dr. Cush has conducted surveys on physician burnout and depression. “Administrative tasks and electronic records are a large part why 24% of people are burning out in medicine.”

Right now, there’s no easy way for many rheumatologists to incorporate regular DAM measures into their EHR system. The extra steps needed to get them there impede physician compliance with the strategy, he and Dr. Curtis agreed. But, Dr. Curtis said, there’s an app for that.

He is the developer of the Rheumatic Disease Activity (READY) measure . The iPad/iPhone app, which is free to download in the app store, is an electronic measurement tool that efficiently captures patient-reported outcomes in RA and other rheumatic conditions.

“This tool really makes it much easier to collect DAM from patients,” Dr. Curtis said. “It is designed for the doc who says, ‘I would take data from patients, just make it easy for me to do that.’ It takes 5-10 minutes to complete, and you get information about pain, fatigue, anxiety, and social interactions and, he said, can be easily integrated into work flow.

On a practice-provided device, the patient answers questions validated on the National Institutes of Health Patient-Reported Outcomes Measurement Information System. It includes a number of electronically scored and validated DAMs and provides trend charts to visualize longitudinal score data and track patient health status over multiple encounters. There are also places to record data about current and past medications.

“The docs input no data, which is the usual deal-killer. All they have to do is figure out how to integrate it into the work flow.”

The ACR is also working on the technology issue, said Kaleb Michaud, PhD , of the University of Nebraska in Omaha.

“ACR has been communicating with the major EMR providers out there to make this easier. We are seeing some tools for iPads and smartphones, as well as paper tools.”

The ACR RISE Registry is another option, said Evan Leibowitz, MD , a rheumatologist in Midland Park, N.J., and an ACR spokesperson.

“RISE is open to all rheumatologists in this country, and ACR has tried to make it as easy as possible. It can interface with most EMRs. All the physician does is collect the data, and it gets transferred to a HIPAA-protected database where it’s analyzed and presented back to the doctors so they can look at all their metrics. It’s currently the least painful way to get involved in a registry, I think.”

But just as techies are rolling out ways to interface DAMs and EHRs, medicine is marching forward. A new blood test called VECTRA DA measures 12 inflammatory biomarkers and may provide all the information needed to make treatment escalation decisions, Dr. Leibowitz said.

“The least painful option will probably be the VECTRA DA score. It’s a single blood test, which we can do easily since we already draw blood. Rather than filling out a RAPID3 [Routine Assessment of Patient Index Data 3] or a CDAI [Clinical Disease Activity Index], we draw the blood, send it to the company, [and] they return us a score that indicates low, moderate, or high disease activity.”

Studies have found that not only is the VECTRA DA score a good clinical management tool, predicting responses, it can also predict impending relapse.

TTT challenges patients, too

Rheumatologists are not the only ones reluctant to embrace TTT. It challenges patients as well, in a number of ways.

“Patients have to be willing to change treatments as often as you need them to, and that can be every 3-6 months, or even more quickly,” Dr. Curtis said. “The cost can be a factor. And a lot of patients are risk averse. They feel there may be more of a downside to switching than a benefit to be gained, especially if they’ve had RA for a while. Maybe they’re feeling a lot better than they were; their disease is still active, but they don’t feel bad enough to want to change medications.”

Researchers have explored these questions.

Last year, Dr. Michaud published a survey of 48 RA patients who were interviewed about their experiences with DMARDs and the feelings that would prompt them to comply with a treatment regimen – or resist one (Arthritis Care Res. 2017 June 2. doi: 10.1002/acr.23301 ).

“For patients’ motivations to accept treatment regimens, two themes emerged,” said Dr. Michaud, who is also codirector of the National Data Bank for Rheumatic Diseases. “One, the desire to return to a ‘normal’ life and, two, the fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.”

The findings confirm one of TTT’s core tenets: involving patients in treatment decisions, Dr. Michaud said in an interview. “A lot of patients in my studies have reached a place of ‘OK-ness’ with their RA. The don’t want to change what they feel is working. They’re afraid of getting worse because they’ve been there and know what that can be.”

Rapid change-ups to new medications are especially intimidating to long-term patients, he said. “This is a very important aspect of resistance to change. The side effects of these medications, both major and minor, are not something that people want to experience.”

Physicians and patients often differ in their interpretation of a side effect, said Liana Fraenkel, MD, another rheumatologist who’s exploring this area.

“As a physician, I’m worried about the rare and extremely rare adverse events – things that are really dreaded, that can be fatal. However, these happen in only a couple out of tens of thousands of patients. On the other hand, there are common side effects that occur in up to 20% of our patients. They’re not a serious threat to health, but they impact quality of life every day with nausea, dizziness, diarrhea, headache, and brain fog. As rheumatologists, we really undervalue these, and guess what? When we ask patients, it turns out that nausea and dizziness and diarrhea are not things that they want in their daily lives.”

Dr. Fraenkel of Yale University, New Haven, Conn., explored this topic in a recently published survey of 1,273 RA patients that sought their concerns about taking triple therapy, biologics, and Janus kinase inhibitors (Ann Rheum Dis. 2017 Dec 15. doi: 10.1136/annrheumdis-2017-212407 ). The survey included seven medication attributes – administration, onset, bothersome side effects, serious infection, very rare side effects, amount of information, and cost – and sought to determine the relative effect of each attribute on patient preference for different treatment options.

“We found five distinct clusters” of patients, Dr. Fraenkel said in an interview. “I will admit I was surprised when I saw the largest group (38%) was most concerned about the cost of their medications. Our assumption is always that the rare and dreaded side effects are the most concerning, but for these patients, cost was the dominant issue. It’s the No. 1 reason patients are noncompliant with their initial treatment recommendations. And with the cost of our biologics, it is a very big deal.”

Her reaction pinpoints an important obstacle in shared decision making: physician bias. “I’d say the vast majority of us argue that the benefit of TTT outweighs the harms. We minimize inflammation, so patients will live longer with less disease impact. But how we get there should be up to the patient. My biases shouldn’t come into play. The decision to intensify is different than the decision about how to intensify. This is where the back-and-forth comes in, making sure the patient understands the pros and cons of escalating or not. If she decided no, she doesn’t incur the risk of a new medication, but she does incur the risk of progressing. The bottom line is that physicians should not bring their biases to the table but describe the facts, the importance of which will be different to different patients who have different goals.”

A patient’s story: Overcoming fear and self-image

Prisha Acharya, PhD, knows a thing or two about rheumatoid arthritis.

As an RA researcher in New York, Dr. Acharya has a vast store of knowledge at her fingertips – everything from long-term treatment outcomes to medication side effects.

But when she was diagnosed with RA last year, at age 38 years, she was overwhelmed. And when she connected with a rheumatologist who wanted to aggressively treat her to a target of low disease activity or even remission, she balked. She became the patient who refuses a treat-to-target strategy.

“He was very clear in communicating the urgency of needing to get the disease under control, and I agreed that was a good thing. But even with all this experience in research, I still felt this resistance. I knew I needed to go aggressive. But I was also worried – worried about the side effects, the long-term effects, the costs. Committing to it was going to make my diagnosis real. I wasn’t ready to do it.”

“Prisha Acharya” is not this patient’s real name. She spoke in an interview on the condition of anonymity because she hasn’t yet discussed her diagnosis with some of her family and friends. In fact, she’s still coming to grips with it herself.

The story of Dr. Acharya’s journey to an RA clinic is one she hears every day in her work. About a year ago, she had some aching and stiffness in her knee, and it spread to her wrists and fingers. Digestive issues arose. She shuffled from doctor to doctor, had knee surgery, visited a gastroenterologist, went on a fibromyalgia medication. She finally broached the topic of a possible autoimmune disorder. By the time she received an RA diagnosis, she could only think of one thing: feeling better.

Her rheumatologist got that. But he also let her know at the first visit that he wanted more for her.

“He said, ‘We’re going to get you feeling better, reduce your pain, and make it so you can get out of bed in the morning,’ but our very first conversation was also about a goal of low disease activity and remission. He explained that we had a brief window of opportunity to make a difference in preventing long-term joint damage and that we had to go for it.”

She was on board with the goal, intellectually at least. However, her gut said something different, especially when they discussed methotrexate.

“There was an association in my head between methotrexate and chemotherapy. I knew it could cause fatigue, nausea, and hair thinning. And the idea of an injection, like I was getting chemo for cancer … it felt very scary.”

As a compromise, she started hydroxychloroquine and shortly after, added sulfasalazine. She was feeling better, but her disease activity scores were still elevated. “My inflammation scores were climbing, and all this time he was saying ‘You have to start methotrexate. You’re going against my advice,’ but I was not emotionally ready. Despite my experience with RA research, I wouldn’t start it.”

With every visit, her rheumatologist patiently built his case for treatment. With every visit, her relationship and trust of him grew.

“Finally, just recently, I did start methotrexate, first with the pill and now the self-injector. I’m on that and the sulfasalazine, but we are reassessing again soon because I still have pain and my disease still isn’t under control. Now we’re going to talk about increasing the methotrexate and adding a new therapy.”

Dr. Acharya’s experience points to the dichotomy between what patients and physicians see as the most important goals and provides a good lesson about how trust and communication can bring those into clinical alignment.

Her rheumatologist set a very clear goal at the beginning of her treatment – one that came with a price tag she wasn’t yet willing to pay. But he also heard and accepted her goal: She wanted to feel better and give herself time to adjust to a new way of life and a new understanding of who she was.

“His language really helped,” Dr. Archaya said. “He acknowledged what I needed – to get the pain and stiffness under control. And as we built our relationship, I was able to hear his side about the urgency of treatment much better. When I was willing to go aggressive, I was also willing to say ‘I have RA.’ It takes a while to get there.”

She had some words of advice to help rheumatologists bridge the gap between what they want for a patient and what that patient wants for herself.

“An open dialogue is really going to help. When patients are voicing their fears, the rheumatologist can reassure them that, if this medicine doesn’t help or if it gives you terrible side effects, we can work together to find another option. Also, it’s so important for the patient to understand the treat-to-target framework from the very beginning. Everything indicates that the earlier we start treatment and set a goal, the better we can control our disease and the better the rest of our life can be.”

The second thing, Dr. Acharya said, is shared decision making. “I want him to tell me the options but also to work with me at arriving at the decision I eventually make.”

Finally, she said, patients need other resources, and rheumatologists can help direct them to find those.

“It’s so important to connect with like-minded patients in patient advocacy groups. The tips that they have given me about medications and dealing with my disease, no doctor could ever give me because patients are the ones that know those things inside-out.”

msullivan@frontlinemedcom.com

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