Clinical Consultations™: Finding Opportunities to Improve the Management of Patients with Connective Tissue Disease-associated Pulmonary Arterial Hypertension (CTD-PAH)

Clinical Consulations CTD/PAH 

Read the most up-to-date information about the latest developments in psoriatic arthritis

Clinical Updates in Psoriatic Arthritis

The impact of psoriatic arthritis on patients’ quality of life and importance of an early, accurate diagnosis.

Expert Perspective on the Management of Psoriatic Arthritis

Rheumatoid Arthritis Quiz

Learn more about the latest developments in rheumatoid arthritis

Focus on Rheumatoid Arthritis

Lana Dykes is the Editor of Rheumatology Network. She is an experienced editor and technical writer with a demonstrated history of working in the banking and publishing industries. She enjoys cooking, yoga, and drawing. 

Prevalence of Gout Reportedly Higher in Black Patients

Despite gout being largely associated with White men, new data suggest gout and hyperuricemia impart a larger burden on other demographic groups, including Black men, Black women, and White women.

Chronic Sleep Deprivation Linked to Higher Risk of SLE

A statistically significant elevated risk of SLE was shown among women with low sleep, depression, and bodily pain when compared with those without these concomitant issues.

Patients with Autoimmune Disease at Greater Complications Risk Following Heart Attack

Investigators believe that coronary intervention, intensified medical therapy, and an aggressive risk factor optimization approach should be available to patients with rheumatic disease presenting with myocardial infarction whenever possible.

Holding Methotrexate After Second COVID-19 Vaccine Dose May Be Best in Psoriatic, Rheumatoid Arthritis

Holding methotrexate after the second COVID-19 vaccine dose is associated with similar immunogenicity and a lower risk of disease flare compared with withholding methotrexate after both vaccine doses.

Autoimmune Disease Increases Risk of Developing Cardiovascular Disease

Although investigations have been performed on the association between inflammatory conditions and cardiovascular events, the effect of different conditions on cardiovascular diseases has not been analyzed on a large scale.

Articles

Take a few minutes to review the most noteworthy studies published on Rheumatology Network in 2022. 

Rheumatology Network: Top Articles of 2022

series, Rheumatology Network interviewed Alfredo Aguirre, MD, to discuss the latest data regarding lupus this year at the American College of Rheumatology (ACR) Convergence 2022, trends in lupus management, and the importance of remission in lupus and its association with improved quality of life and improved outcomes in this patient population. Aguirre is Assistant Clinical Professor at the University of California, San Francisco.

What studies or new data related to lupus stand out to you most prominently in 2022?

I think one theme that came out in lupus this year was safety of some of our newer agents, newly approved agents, and agents approved for new indications, like belimumab for lupus nephritis, anifrolumab for active lupus, and voclosporin for lupus nephritis. There were some data presented at the ACR Convergence, as well as publications, that were overall reassuring for safety and durability of response.

Another theme was the importance of remission in lupus. Data has been coming out about remission and its association with improved quality of life, improved mortality in lupus, and improved outcomes, such as reduced organ damage. The concept of remission is relatively new and may be a new treatment target for us in clinical settings.

There was also an interesting presentation at the ACR this year on hydroxychloroquine and lupus flares. They studied the association between lowering a dose of hydroxychloroquine in patients and subsequent flares. It was a complicated study design, but basically what I got out of that study is that if I inherited a patient, for instance, who was on a high dose of hydroxychloroquine and who is above the threshold record that's recommended now by the new guidelines, I would not reduce their dose unless they have stable disease as to not increase their risk of theoretical flare. There needs to be more studies to confirm this risk, but it was a well-designed study.

Have you noticed any overarching trends in lupus management and treatment over the past year?

The major thing that has changed over the past few years is a move to multi-target therapy in lupus nephritis, which is the idea of prescribing multiple immunosuppressants instead of 1 or 2 on diagnosis. I think the field is still struggling about when to do that and how to sequence medicines. We’re all still kind of figuring out what to do about that problem. It's not unique to this year, but it is a trend that is relatively new that we have this option of, in the spirit of improving outcomes for patients with lupus, we can add, in many cases, a second steroid sparing agent to a regimen and many times it's very safe. Like I said, we've shown a lot the safety of these of these agents, for instance, like belimumab for lupus nephritis.

What are the most pressing issues and lupus that you hope to see addressed in 2023?

 I think it's troubling that the remission rates for lupus nephritis are relatively low and relapse rates remain relatively high. We still don't understand who would benefit from what therapy and we don't have a good idea of precision medicine in lupus. Another pressing need is reducing steroid exposure.

Alfredo Aguirre, MD, discusses the latest data regarding lupus this year at the American College of Rheumatology (ACR) Convergence 2022, trends in lupus management, and the importance of remission in lupus. 

Lupus Year in Review: 2022

series, Rheumatology Network interviewed Ayman Askari, MD, to discuss the recent trends, studies presented at the American College of Rheumatology (ACR) Convergence 2022, and the pressing issues that face rheumatologists treating rheumatoid arthritis moving into 2023. He stresses the importance of vaccination, particularly the COVID-19 vaccination, in patients with rheumatic diseases, like rheumatoid arthritis, and believes comparisons between Janus kinase (JAK) inhibitors should be more thoroughly researched in the upcoming year. Askari is a consultant rheumatologist at the Robert Jones and Agnes Hunt Orthopedic Hospital.

To touch on rheumatoid arthritis more broadly in 2022, have there been any new studies or data presented this year that stands out to you?

I attended a few talks at the ACR regarding upadacitinib, which is a product by AbbVie. In the SELECT and SELECT-COMPARE trials, as well as other various studies, it seems to be an effective product.

There were also seminars on psoriatic arthritis and talks on anti-interleukin 23, but as far as rheumatoid arthritis, I would focus on upadacitinib and JAK inhibitors. I think in the future, rheumatologists are going to be using more JAK inhibitors because it's an oral tablet and it has a very short half-life. So that will influence my future practice.

Have you noticed any overarching trends in rheumatoid arthritis management and treatment over the past year?

 I wouldn't say that there are major changes. We just came out of COVID and COVID has affected our practice. So, we are talking a lot about vaccination and COVID vaccination. Medications that can suppress the immune system, like rituximab, for example, can make patients more prone to COVID. But I would say there are no fundamental issues with rheumatoid, apart from the more prevalent use of JAK inhibitors.

What are some of the most pressing issues in rheumatoid arthritis that you would hope to see be addressed or receive a greater focus in 2023?

I think vaccination for COVID and for herpes zoster is going to be focused on in 2023. The use of JAK inhibitors and the comparison between various JAKs is an issue for discussion. We have JAK1, JAK2, JAK3, and there is a Tyrosine kinase 2 (TYK2) also. These new modalities in addressing immune suppression are going to be researched more or observed more. I mean, it's already been researched and published, but side effects such deep vein thrombosis (DVT) and herpes zoster, which are always on our minds, could be observed more in the upcoming year.

Is there anything else that you would like our audience to know before we wrap up?

Well, I saw something in the exhibition regarding blood tests that some of your labs are producing. Particularly, one in California was producing rapid autoimmune tests which interests me if they are doing it at a low cost. That might be an advantage for the public in the future, not necessarily just for rheumatoid arthritis but for all the connective tissue disorders. That’s definitely one of the things that caught my eye during the recent conference.

Ayman Askari, MD, discusses the recent trends in rheumatoid arthritis, studies presented at the American College of Rheumatology (ACR) Convergence 2022, and the pressing issues that face rheumatologists moving into 2023.

Rheumatoid Arthritis Year in Review: 2022

Patient-reported outcomes (PROs) have been highlighted in rheumatology research and clinical practice in recent years, underscoring that the opinions of patients can greatly impact the treatment and management of these patients. This is particularly important in marginalized patients, such as women and Black and Hispanic patients, and certain conditions, such as lupus, which disproportionately affect these patient populations. More and more, rheumatologists are seeing the benefits of utilizing PROs in a clinical setting as a guide to help inform and personalize analgesic strategies for patients.

Evaluating a Patient’s Self-Evidence when Developing a Treatment and Management Plan

Andrea Chadwick, MD, Medical Director of Swing Care and Associate Professor in the Department of Anesthesiology, Pain, and Perioperative Medicine at the University of Kansas School of Medicine, emphasized that the number of PROs have expanded in recent years, enabling doctors to assess patients with fibromyalgia more thoroughly. Whereas in the past, rheumatologists relied on a tender point exam and the Beck Depression Inventory (BDI), new scales including catastrophic thinking, resilience, and stress have been added to the arsenal of patient evaluation.

“The makeup of each fibromyalgia patient is different in terms of what their pain phenotype is, and PROs are great at honing in on those specific characteristics for patients,” Chadwick explained. “For example, you can identify whether a particular fibromyalgia patient has more difficulty with fatigue and sleep versus another fibromyalgia patient who may struggle with significant sensitivity to their skin and poor physical functioning.”

Similar to fibromyalgia syndrome, certain rheumatic diseases, such as lupus, disproportionately affect women and minorities, who often express feeling unheard. PROs are an essential tool to ensure that rheumatologists can hear the concerns voiced by their patients and validate their experience. As some patients have reported feeling reluctant to share their experience or symptoms if not asked directly, being able to use a tool that measures and tracks symptom burden, health-related quality of life, functional status, behaviors, and overall health care experience is vital.

“There's a discrepancy between what patients feel like is important to them and what clinicians think is important to them, which is probably true in all of medicine,” Alfred Aguirre, MD, Assistant Clinical Professor at the University of California, San Francisco, hypothesized.

While other diseases and conditions have more clear-cut definitions of remission and management, in rheumatology, a clinician generally has to rely on a variety of different data inputs, including clinical examinations and integration of data elements to ascertain if a patient’s condition is under control, thus making it a bit more subjective when compared with other fields. As patients often have different symptom manifestations, it’s important to gain the perspective of the patient and use that as a part of the management plan.

“Sometimes what the doctor thinks is at odds with what the patient feels is important,” Aguirre explained. “I think that insight has driven a lot of the research on patient-reported outcomes. And we have discovered a lot of interesting things, such as the importance of fatigue in systemic lupus erythematosus (SLE), for instance, and how that is such a disabling and mysterious symptom that we still don’t fully understand.”

Additionally, rheumatic diseases, particularly in lupus and fibromyalgia, are often quite heterogenous. By acquiring a patient’s perspective, a rheumatologist is able to more effectively understand not only the disease, but also their goals and aspirations when it comes to their health and life, in addition to the unique factors related to care.

“No 2 patients have the same ‘brand’ of lupus or the same experience when it comes to their disease or how it impacts their life,” Saira Z Sheikh, MD,Director of the Clinical Trials Program at the University of North Carolina at Chapel Hill (UNC) Thurston Arthritis Research Center, the UNC Rheumatology Lupus Clinic, and Vice-Chair of the Lupus Clinical Investigators Network, emphasized. “How can we effectively care for our patients, if we do not assess or measure what they are experiencing and what is most impactful to them?”

Aguirre underscores that rheumatologists should understand that there are key domains outside of what is normally asked during clinical encounters. Patient-reported outcome measures, including ones that focus on cognitive function and sleep, which are often highly rated by patients with SLE, are not only easy to implement via questionnaires, but can also be used to track a patient’s progress over time.

“In the last 3 to 4 years, general research has been focusing more on patient-reported outcomes because it is the true representation of what's going on in real life,” Ayman Askari, MD, consultant rheumatologist at the Robert Jones and Agnes Hunt Orthopedic Hospital, explained. “My patients are complicated. In trials, they often choose patients who have a single illness or disease and are similar in age. Real world data represents a better value.”

Patient Advocacy Organizations Shed Light on the Importance of Patient Perspective

In recent years, patient advocacy groups, such as 

, have focused attention on the patient experience and using self-evidence to help patients manage their conditions and influence further research in this field. These organizations provide a necessary source of independence within their disease journey.

“As an autoimmune patient myself, I know about the daily struggle so many patients face in coping with uncontrolled symptoms because I’ve been there,” Mette Dyhrberg, founder of the self-advocacy platform Mymee explained.

Using a simple Excel spreadsheet, Dyhrberg, who has struggled with multiple autoimmune diseases for most of her life, began systematically tracking symptoms, habits, stress levels, and diet to discover any patterns and identify her personal triggers. After learning how to manage her conditions, she became determined to help patients like herself uncover their own unique triggers using her approach, only more quickly and efficiently via a decade-long journey of building a clinically validated solutions focused on patients struggling with uncontrolled symptoms, despite treatment.

Further, recent studies from CreakyJoints and the Global Healthy Living Foundation presented at the American College of Rheumatology (ACR) Convergence 2022 realize the benefit of taking PROs into consideration in rheumatology research by examining the specific 

patient perspective of support and educational needs

 of LatinX and Hispanic patients with rheumatoid arthritis and well as 

how to best prioritize patient-centered research to reduce vaccine hesitancy

A recent research program developed by Lupus Therapeutic (LT), called the 

LT Patient Advocates for Lupus Studies (PALS)

 program, serves as a model of patient-engaged research and provides evidence of a practical program that can be used to increase participation of underrepresented and ethnically diverse patients in lupus clinical trials.

Sheikh emphasized that the research team at LT and LRA makes an intentional effort to incorporate the patient voice into all initiatives they design.

“We work closely in partnership with patients, recognizing them as key stakeholders, and believe that clinical trials, clinical research, and health care in general needs to be centered around the patient experience,” she stated.

Experts agree that there is a need to implement PROs in routine clinical settings as a strategy to gain information on a population level to improve health and wish that these tools were more readily available for easy use in clinics. However, Chadwick, among others, expressed that more practitioners are recognizing the value of assessing the patient perspective in recent years.

“Moving into the future, the winning combination is utilizing both PROs and the physician’s assessment collectively in order to assess disease activity, quality of life, and effectiveness of treatment and therapeutics both in research and in clinical practice,” Sheikh concluded.

“There's a discrepancy between what patients feel like is important to them and what clinicians think is important to them, which is probably true in all of medicine,” Alfred Aguirre, MD, stated. 

A Growing Trend Towards Incorporating Patient-Reported Outcomes in the Treatment, Management of Rheumatic Diseases 

series, Rheumatology Network interviewed Andrea Chadwick, MD, to discuss the top highlights of fibromyalgia in the year 2022. She noted that recent research has focused on more complementary and alternative therapies, highlighting the potential importance of utilizing a multidisciplinary approach when managing patients, including cognitive behavioral therapy and acceptance and commitment therapy. Both physical and emotional functioning are becoming a more mainstream approach to treatment, instead of solely attempting to alleviate painful symptoms. Chadwick is Medical Director of Swing Care and Associate Professor in the Department of Anesthesiology, Pain, and Perioperative Medicine at the University of Kansas School of Medicine in Kansas City, Kansas.

Were there any studies or new data related to fibromyalgia that stands out to you when looking back on 2022?

There hasn’t been much in the way of drug development in 2022. However, I think the literature is becoming more and more aware of the impact that more complementary and alternative treatments can have for fibromyalgia and the importance of cognitive behavioral therapy, acceptance and commitment therapy, and an overall focus on multidisciplinary care.

Things have been very heavily interventional, focusing on what we can do to treat peripheral problems. Where I've seen the literature go is looking at that overall view of the patient, and making sure that we're coming up with not only care in the physical sense (making sure that patients are being active and trying to meet their goals for movement), but also taking into account some of the more novel therapies for fibromyalgia.

The seminal work for things like low-dose naltrexone came out probably about a decade ago, but we're finding more and more the utility of that drug, not only in fibromyalgia but any central sensitization syndrome and even in some autoimmune disorders.

I haven't seen much in the way of new drugs that have come out, but I have seen some reviews on low-dose naltrexone and case reports for low-dose naltrexone this year that have been worthy of reading.

In the review articles, I've seen a focus on multidisciplinary care, including that behavioral component, and getting to the point where the patient can accept that the real end goal of treatment and fibromyalgia is more of an acceptance of values and goals in their lives and how to marry that with their pain as opposed to complete elimination of pain.

One of the reasons why I love covering fibromyalgia is because there's such an emphasis on taking integrative approach to treatment. It's interesting to be able to combine all these tools to help manage and treat patients.

Absolutely. And even thinking outside of the box and looking at things that may not fit the norm. As medical doctors, we're traditionally educated on medications and certain types of therapies. But I recently finished a study looking at heat therapy in fibromyalgia patients based on patients telling me that heat made them feel better. And so, I received an internal grant at the University of Kansas to look at how hot water immersion multiple times a week might improve pain and physical functioning.

I partnered with a basic scientist who does work in essentially heat shock proteins. She runs a lab where she looks at the effect of heat on glycemic control and metabolic function in rodent models. We looked at heat shock protein levels and inflammation levels in humans. What we found, and we're getting ready to hopefully publish soon, is that the heat therapy over a course of 4-week treatment was very helpful for reducing pain and significantly improving physical functioning. Interestingly, the blood markers for heat shock protein and heat shock protein levels and inflammation appeared to show that the heat was helping to reverse some of the proinflammatory states of these patients. Who would have thought hot tub therapy would potentially be a treatment option for patients? But you know, I think the lived experience of patients, using the stories they tell us, and coupling it with science can come up with some really neat and novel information and innovation.

 Have you noticed any overarching trends in fibromyalgia management and treatment over the past year?

I think the focus really has been on medications in the years past. When I was in training, you had your 3 FDA approved agents, and you could try off label usage of some medications. But a lot of times, at least in the training I had, there wasn't a whole lot that could be used to help patients and the importance of movement and physical activity, especially the behavioral care.

There are 3 silos of treatment options for fibromyalgia patients: physical modalities, pharmacologic modalities, and behavioral modalities. The behavioral component has really been shaping up to be one of the most important and more significant roles in fibromyalgia treatment, at least in my own practice. In the last half decade, many comprehensive pain programs, or even just health systems in general, are employing people who have expertise in things like cognitive behavioral therapy, as well as acceptance and commitment therapy. And I think that the patients themselves really have found value in those types of therapies.

So often we focus on symptom reduction as our ultimate goal as physicians. But what's interesting about the dogma that I've been witnessing over the last few years is this notion that the overall functioning of that person is more important, and that that includes physical functioning, yes, but emotional functioning, and improvements in fatigue and sleep. Focusing more on the whole person as opposed to just painful symptoms is really where I think fibromyalgia care is headed.

What are some of their most pressing issues in fibromyalgia that you hope to see addressed or receive a greater focus on in 2023?

I think that's a great question. There's still so much to know about how fibromyalgia develops in some individuals. And I think, in 2023, we're kind of in this post-COVID era. I'd like to see some research develop and treatment strategies be addressed for patients who did not have fibromyalgia-like symptoms or other co-occurring pain syndromes prior to their COVID infection and to understand those patients. How did they develop that fibromyalgia phenotype when they did not have it before their COVID infection? In my own practice, I've noticed that COVID infections for patients who already have fibromyalgia can lead to either a significant prolonged post-COVID course or in others they recover quite quickly from it.

I think it's rather timely too, as we're kind of coming out of the significant pandemic portion of the Coronavirus, that we're starting to understand how it's impacting patients with newly developed fibromyalgia as a result of their prior COVID infection or what the natural courses for those patients or for patients who developed COVID while they already had fibromyalgia.

But outside of the Coronavirus impact in the fibromyalgia world, I think focusing on research on novel treatments, whether they be pharmacologic or non-pharmacologic, are of desperate need. Because providers oftentimes feel that their armamentarium for helping address symptoms for fibromyalgia patients can be quite limited with the currently available number of FDA approved drugs. Ultimately, the amount of side effects we see with FDA approved and non-FDA approved drugs can oftentimes limit or preclude their use in patients with fibromyalgia.

Is there anything else that we haven't addressed that you would like our audience to know?

The readers should continue to look for good treatment options for their patients that involve improving access to care for patients with fibromyalgia. Fibromyalgia still, generally speaking, lacks a medical home. And so, I would encourage researchers or clinicians who are reading this feature to continue to focus on making sure that these patients are heard, seen, and validated and are being given the best care possible and being referred for fibromyalgia-specific care as much as possible.

Current literature is trending towards exploring the impact of complementary and alternative treatments for fibromyalgia and an overall focus on multidisciplinary care. 

Fibromyalgia Year in Review: 2022

Gout Linked to Higher Risk of Developing Osteoporosis

Results indicated that the incidence of osteoporosis increased up to 4 times in younger male patients with gout when compared with those without gout.

Metabolic Syndrome Identified Among Risk Factors for Early Onset Gout in Men

The incidence of gout, the most common type of inflammatory arthritis in men, has increased globally in recent decades.

Self-Advocacy Platform Allows Patients with Autoimmune Diseases to Discover Triggers, Improve Disease Management

Mymee, a self-advocacy platform, utilizes technological innovation, such as self-tracking, data analytics, and expert health coaching, to improve access and offer hope to these patients by uncovering their unique triggers, managing disease flares, and improving quality of life.

Addition of TNFi, Triple Therapy Improved Vascular Inflammation in Patients with RA

Although previous studies have indicated differential effects on cardiovascular risk between immunomodulators, results showed similar reductions across both treatment groups.

Can a Peer Education Program Improve Patient Engagement and Health Equity in Lupus Research?

Enrollment in clinical trials across all disease states, particularly in lupus, continues to be an ongoing challenge.

Take 5 minutes to catch up on Rheumatology Network's top articles from December 2022.

Rheumatology Network's Month in Review: December 2022

series, Rheumatology Network interviewed Theodore Fields, MD, FACP, to discuss the top highlights of gout in the year 2022. Fields discusses the stand out studies, including the MIRROR trial, a study pinpointing the role of lubricin deficiency in the pathogenesis of gout, and a Korean study that compared febuxostat and allopurinol treatment and the impact they had on adverse cardiovascular reactions. He goes on to discuss regulatory news updates and the most pressing news issues that he hopes will be addressed in 2023. Fields is Attending Rheumatologist, Professor of Clinical Medicine, Weill Cornell College of Medicine, Hospital for Special Surgery, and a medical advisor to CreakyJoints.

What studies or new data related to gout stand out most when looking back at 2022?

The MIRROR trial showed success in a randomized, controlled trial for the combination of methotrexate and pegloticase in reaching goal (71%) in significantly more patients than pegloticase alone (39%).This is a significant advance, since the potent medication pegloticase only succeed in prior trial at approximately 40%, as in this trial, due to antibody formation. Methotrexate appears able to block this antibody formation.Infusion reactions were also markedly less in the methotrexate group.

A population study in Korea looked at ~160,000 users of febuxostat vs allopurinol in terms of adverse cardiovascular (CV) reactions, with propensity score matching for multiple co-morbidities.

 Febuxostat was found to be non-inferior to allopurinol for risk of CV events. There was actually an unexpected finding of 16% reduced risk of all-cause mortality for febuxostat vs allopurinol. This was especially interesting since the FAST trial

 had also found a trend in this direction, as opposed to the CARES trial4 which had found a death rate higher with febuxostat. Putting all the data together, the concerns about febuxostat appear more and more to not be significant, and this medication can be used when needed without excessive concern about cardiovascular issues.

A study looked at the effectiveness in stopping gout erosions of lowering the uric acid goal in severe gout from <5.0 to < 3.4.5 This was important because we had no prior studies of urate goal and its outcomes. At 2 years, they did not find significant difference in gouty erosions between the <5.0 and the <3.4 group, and they found it challenging to get to the <3.4 goal. At 2 years, the tophus count and index tophus area were less in the <3.4 group, but not statistically significantly different. There were 52 patients in each group.Overall, it was a major contribution to look at a 2 year outcome of different gout treatment goals, but I don’t think this study is sufficient to rule out considering a goal even less than <5.0 for patients with especially severe tophaceous gout.

Robert Terkeltaub, MD, and a large group of authors reported that lubricin deficiency may be a significant player in the pathogenesis of gout.6 They studied a young adult woman with erosive urate-induced erosion with normal uric acid level, seeking gout mechanisms that were independent of uric acid. In vitro, they found blunted urate precipitation by lubricin. The patient studied has markedly decreased serum lubricin and genetic studies found provocative results for further analysis. This study raises the question as to whether strategies to increase lubricin could be future therapeutic options in gout.

What regulatory news or updates related to gout stand out most when looking back at 2022?

The major issue was the US Food and Drug Administration (FDA) approval of the combination of methotrexate and pegloticase. This was especially based on the findings of the MIRROR study, as discussed above.

Two years removed from the ACR's latest gout guidelines, how have you seen the new recommendations impact care?

The guidelines seem to increase my rheumatology colleagues interest in checking the HLA-B*5801 marker in patients with Asian (but not Japanese) background, and to also consider this testing in African American patients. I believe that the guidelines have moved the primary care community more towards a treat-to-target approach to gout, rather than the treat-to-symptoms approach noted in the American College of Physicians' (ACP) guideline. Also, since the ACR guidelines came out 2 years ago, there have been several articles published further demonstrating the benefits of a treat-to-target approach to gout, so hopefully any future ACP guideline will recommend this approach.

What are the most pressing issues in gout you hope to see addressed or receive a greater focus in 2023?

Longer-term studies of larger number of gout patients are ongoing and should help to further support a treat-to-target approach, and better define that target. As discussed above, I still feel that a very intensive urate lowering approach is likely helpful in shrinking tophi faster, but we need proof in appropriate studies.

Great efforts have been made to educate the physician community, especially the primary care community, about the dramatic benefits to gout patients from an aggressive and targeted approach. Still, many studies still show less than 50% of gout patients receiving appropriate urate-lowering therapy. The educational process needs to continue!

Botson JK, Saag K, Peterson J, et al. A Randomized, Placebo-Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings [published online ahead of print, 2022 Sep 13]. 

. 2022;10.1002/art.42335. doi:10.1002/art.42335

Shin A, Choi SR, Han M, et al. Cardiovascular safety associated with febuxostat versus allopurinol among patients with gout: Update with accumulated use of febuxostat. 

. 2022;56:152080. doi:10.1016/j.semarthrit.2022.152080

Mackenzie IS, Ford I, Nuki G, et al. Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial. 

. 2020;396(10264):1745-1757. doi:10.1016/S0140-6736(20)32234-0

White WB, Saag KG, Becker MA, et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. 

. 2018;378(13):1200-1210. doi:10.1056/NEJMoa1710895

Dalbeth N, Doyle AJ, Billington K, et al. Intensive Serum Urate Lowering With Oral Urate-Lowering Therapy for Erosive Gout: A Randomized Double-Blind Controlled Trial. 

. 2022;74(6):1059-1069. doi:10.1002/art.42055

Elsaid K, Merriman TR, Rossitto LA, et al. Amplification of inflammation by lubricin deficiency implicated in incident, erosive gout independent of hyperuricemia [published online ahead of print, 2022 Dec 1]. Arthritis Rheumatol. 2022;10.1002/art.42413. doi:10.1002/art.42413

Theodore Fields, MD, FACP, discusses the most important gout studies in 2022, regulatory news, and the most pressing issues surrounding gout moving into 2023. 

Gout Year in Review: 2022

Results of the National Residents Matching Program (NRMP) indicated that 75% of eligible candidates interested in adult rheumatology and 96% of eligible applicants interested in pediatric rheumatology were able to be successfully matched to fellowship programs in 2023. However, although the percentage of available adult programs filled 97.8% of available fellowship slots, pediatric programs only filled 62.8% (26 fellowship positions out of a total of 43 available positions), thus suggesting a direct need to increase interest in pediatric rheumatology.

“Other pediatric specialties such as pediatric pulmonology, nephrology, infectious disease, and endocrinology also had a significant number of unfilled positions; in contrast, the relatively new field of pediatric hospital medicine filled nearly all open positions, which may hint at the goals and training interests of current pediatric applicants,” Beth Marston, MD, chair of the American College of Rheumatology’s Committee on Training and Workforce Issues (COTW), stated. “Many potential barriers have been suggested, including inadequate exposure and mentorship within these specialties, long periods of required training, and lower ultimate compensation for pediatric specialists, which might be targets for future work to improve our pediatric specialty workforce.”

Workforce shortage projections, highlighted in the American College of Rheumatology’s (ACR) 

, have plagued rheumatology in recent years. In a 

, published earlier this year, Andrew Concoff, MD, Executive Vice President and Chief Value Medical Officer at United Rheumatology, has described this trend as the “great resignation,” in which maintaining a healthy, comfortable staff at the independent private practice level is becoming increasingly more difficult. The workforce shortage, which is exacerbated by the large number of rheumatologists planning to retire in the upcoming years, is “severe enough that the expectation is that for every rheumatologist we have, there will be an equal number that we lack,” Concoff explained.

However, the number of adult fellowship matches during the Specialty Match Days has grown over the past 5 years and interested candidates have surpassed the number of positions. The ACR believes this may indicate a need to increase fellowship training opportunities. The ACR’s Workforce Solutions Committee continues to focus on increasing fellowships and positions, with a specific concentration on geographically underserved areas.

“This year was the first time that the adult and pediatric fellowship Match dates aligned, allowing participants the opportunity to apply to and rank both adult and pediatric training programs in a single rank list by a dual-trained applicant or by a couple. This change has been welcome, as it facilitates the application process for a number of candidates,” Marston explained.

The ACR continues strive to increase exposure to rheumatology earlier in training, better understand the barriers surrounding training in pediatric rheumatology and pediatric and combined internal medicine.

The NRMP, established in 1952, utilizes an algorithm to fill available training positions at teaching hospitals in the United States by aligning the preferences of both applicants and program directors.

Potential barriers to an interest in pediatric rheumatology include inadequate exposure and mentorship within these specialties, as well as long periods of required training and lower compensation for pediatric specialists. 

ACR Identifies an Ongoing Need to Increase Interest in Pediatric Rheumatology 

Katie Robinson is a medical writer. She covers various health and medical topics for a professional audience.

In patients with psoriatic arthritis (PsA), a correlation was found between immune cell types resembling four immune cellular phenotypes in the condition, according to a study published in 

The results imply “the possibility of improving PsA patient stratification based on both clinical and immune cellular phenotypes,” Marie Skougaard, MD, of The Parker Institute, Bispebjerg and Frederiksberg Hospital in Frederiksberg, Denmark, and colleagues, stated.

In the study, the researchers explored the interaction between immune cell subtypes composing the immune response driving PsA. They evaluated the possible differences in immune cellular phenotypes, and also examined associations between emerging immune cellular phenotypes and PsA disease outcomes.

The researchers used multicolor flow cytometry on the peripheral blood collected from 70 patients (39 females, age: 51.5 years, disease duration: 4 years) with PsA to determine the frequencies of 9 immune cell subtypes. Principal component analysis was completed on the immune cells to established cellular phenotypes. Meanwhile, Disease Activity in Psoriatic Arthritis (DAPSA) and Psoriasis Area Severity Index (PASI) were retrieved to assess the associations with individual cellular phenotypes.

The researchers identified 4 components using PCA, explaining 66.6% of the variance in the dataset, resembling 4 immune cellular phenotypes. Component 1, which explained 25.6% of the variance with contribution from T-helper 17 cells (Th17), memory T regulatory cells (mTregs), dendritic cells and monocytes, was associated with longer disease duration and higher DAPSA. Component 2, which explained 18.4% of the variance, was driven by Th1, naïve Tregs and mTregs and was associated with shorter disease duration. Component 3 which explained 12.5% of the variance, was driven by both Th1, Th17 and CD8+ T cells. Component 4, which explained 10% of the variance, was characterized by a reverse correlation between CD8+ T cells and natural killer cells.

The study also aimed to assess immune cell characteristics evaluating possible differences in cellular phenotypes in the patients initiating new medical therapy. Comparing treatment groups, meaningful differences were only found when comparing concomitant conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) and the number of previousbiological DMARDs. Investigators explained that this, together with the difference in disease duration (7.75 years) for interleukin 17 inhibitors (IL-17i) initiators compared with that for tumor necrosis factor inhibitors (TNFi) (3.67 years) and methotrexate (3.13 years) initiators, may be explained by treatment guidelines in Denmark, which include TNFi being the first line biological DMARD after conventional synthetic DMARD failure, while IL-17i would be considered after TNFi.

While the results add to the discussion of stratified treatment based on immune cellular phenotypes, “additional understanding of immune cellular response mechanisms in larger cohorts is needed before treatment targeting individual immune cellular phenotypes will be possible,” investigators concluded.

Skougaard M, Ditlev SB, Stisen ZR, Coates LC, Ellegaard K, Kristensen LE. 

Four emerging immune cellular blood phenotypes associated with disease duration and activity established in Psoriatic Arthritis

. 2022;24(1):262. Published 2022 Nov 29. doi:10.1186/s13075-022-02956-x

The results imply the possibility of improving patient stratification based on both clinical and immune cellular phenotypes.

Emerging Immune Cellular Blood Phenotypes Linked to Disease Duration, Activity in Psoriatic Arthritis

Overlapping symptomology and diagnostic prevalence of fibromyalgia syndrome (FMS) and connective tissue disorders, such as hypermobile Ehlers-Danlos Syndrome (hEDS), Generalized Joint Hypermobility (GJH), and Hypermobility Spectrum disorders (HSD), were reported in a study published in 

 Investigators urge clinicians to reflect on both diagnoses to ensure an accurate diagnosis and management plan.

“In the absence of clear understanding of some musculoskeletal conditions and in the presence of similarities of definitions, pathogenesis, and symptomatic features in musculoskeletal practice, it is necessary to understand concomitant diagnoses in potentially overlapping conditions,” investigators explained.

Investigators systematically searched the bibliographic electronic database MEDLINE to identify observational research studies in which adult patients were screened for FMS and hEDS, HSD, and GJH and were compared regarding musculoskeletal and non-musculoskeletal manifestations, as well as diagnostic prevalence. Study quality was evaluated by 2 reviewers using the National Institute of Health (NIH) Quality Assessment tool for case control studies and the Jonna Briggs Critical Appraisal checklist for the single group studies.

Of the 85 potential studies identified, 11 were ultimately included (9 case-control studies and 2 single group studies). According to the NUH Quality Assessment tool, 3 studies were rated as “poor,” 4 were rated as “fair,” and 2 were rated as “good.” Using the Joanna Briggs Institute checklist, 1 study was rated as “moderate” quality and the other was deemed “high” quality.

A concomitant diagnosis of hEDS/HSD and FMS ranged from 68%-88.9%, while GJH and FMS prevalence ranged from 8%-62.4%. Both the prevalence and severity of patient-reported and objective features were similar between those with hEDS/HSD and FMS, such as joint swelling, joint pain, neurological symptoms, muscle weakness, gastrointestinal issues, pain, function, and quality of life. For those with GHS and FMS, similarities of shared symptoms included pain, psychological impact, total myalgia score, and tender points count.

The study was limited by not having a previous similar systemic review for comparison. Further, the risk of bias, which was only rated as “low” in 3 of the studies, should be noted. Although the structure of the review was divided into hEDS/HSD, which are often symptomatic, and GJH, which is often asymptomatic, most of the reviewed studies evaluated patients who had a primary diagnosis of FMS. Investigators note that they could not ascertain whether the clinician’s background, experience, and knowledge of connective tissue disorders could impact diagnosis. Therefore, future research should focus on examining this aspect, as it is highly recommended that screening for both conditions should be considered, and clinicians can then make a diagnosis on a case-by-case basis and personalize management plans.

“FMS and connective tissue disorders were found to be highly associated in terms of prevalence and symptomatic features,” investigators concluded. “Therefore, clinicians should be aware of the potential overlap between FMS and hEDS/HSD and GJH. The diagnosis of these conditions relies on widespread pain, however, considering tender points in the examination could lead to the diagnosis of FMS, and considering joint hypermobility in the examination could lead to the diagnosis of hEDS/HSD.”

Alsiri N, Alhadhoud M, Alkatefi T, Palmer S. The concomitant diagnosis of fibromyalgia and connective tissue disorders: A systematic review [published online ahead of print, 2022 Nov 17]. 

. 2022;58:152127. doi:10.1016/j.semarthrit.2022.152127

Fibromyalgia syndrome and connective tissue disorders were found to be highly associated in terms of both prevalence and symptoms.

Study Highlights Symptom Similarity Between Fibromyalgia and Connective Tissue Disorders 

Ingrid Torjesen is a UK-based freelance health journalist with more than 30 years of experience in health and medical communications. She works for numerous publications including Rheumatology Network, the BMJ and the Economist’s Intelligence Unit. Before her freelance career, her staff jobs included news editor of both Pulse and GP (the two leading UK weekly titles for primary care doctors), and opinion and features editor of the Health Service Journal (the UK’s leading health policy title). She also spent a few years working in Australia, including on Australian Doctor.

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A bidirectional causal relationship exists between psoriasis, psoriatic arthritis (PsA) and Crohn’s disease, but not between psoriasis, PsA and ulcerative colitis, according to a study published in

“The results suggest a compelling rationale for the clinician to detect the earlier potential development of these diseases,” Yang Sun, department of orthopedics at The First Hospital of Jilin University in Changchun, Jilin, China, and colleagues, stated.

While there is a link between PsA and inflammatory bowel disease (IBD), consisting of ulcerative colitis and Crohn’s disease, it is difficult to determine whether PsA and IBD are causally related. Moreover, anti-tumor necrosis factor-alpha used to treat patients with IBD is a risk factor for psoriasis.

In this study, investigators evaluated the potential causal relationship between psoriasis, PsA, and IBD using the summary statistics from the public available genome-wide association (GWAS) studies’ data. The largest GWAS of psoriasis included 4510 cases, and PsA included 1637 cases, with 212,242 controls each. The largest GWAS for ulcerative colitis included 2251 cases and Crohn’s disease included 657 cases, with 210,300 controls each. All cases were European individuals from the FinnGen biobank.

Genetically predicted psoriasis and PsA were associated with a 35% and a 31.9% increased risk of Crohn’s disease, respectively. Similarly, genetically predicted Crohn’s disease was associated with a 42.5% increased risk of psoriasis and a 44.8% increased risk of PsA, respectively. No correlations were found between ulcerative colitis and psoriasis or PsA.

The results align with previous studies and could be explained by the fact that psoriasis, PsA and Crohn’s disease have a similar pathogenesis. Seven non-human leukocyte antigens (HLA) susceptibility loci shared by Crohn’s disease and psoriasis were found, and 4 previously identified common risk loci were affirmed, according to the study. While Crohn’s disease and ulcerative colitis have similar clinical signs, genetic risk loci and immune pathways, they have distinctive properties that may explain the discrepancy in their link with psoriasis and PsA, investigators explained.

A limitation of the study was that the population only included individuals of European ancestry. “More studies should be conducted to verify the applicability of these results to other ethnicities,” investigators concluded.

The causal relationship between psoriasis, psoriatic arthritis, and inflammatory bowel diseases

. 2022;12(1):20526. Published 2022 Nov 28. doi:10.1038/s41598-022-24872-5