That's debatable! Doctors dissect 5 hot topics in rheumatology

By Naveed Saleh, MD, MS | Fact-checked by Barbara Bekiesz
Published June 15, 2023

There's a well-worn adage in rheumatology circles that if two experts evaluate the same patient, they'll almost certainly come up with three conflicting opinions. Controversies and lively debates are pervasive throughout the field.

In this special report, MDLinx examines five controversies in rheumatology today, bringing in the expert perspectives of two esteemed MDLinx medical advisors: David Ozeri, MD, FACP, FACR, clinical academic rheumatologist at Sheba Tel HaShomer City of Health Medical Center in Israel, and Anita Chandrasekaran, MD, MPH, rheumatologist at Hartford HealthCare Medical Group in Connecticut.

Rheumatology is a rapidly advancing, but relatively young subspecialty. Accordingly, an understanding of the pathophysiology, treatment, and classification of rheumatic disease is still emerging.

Plus, the lack of protocol-defined guidelines for treatments gives rise to differing practices—and, yes, opinions—all paving the way for a better understanding of rheumatic diseases and more informed patient care.

Controversy #1: Treating pre-RA

In patients with an absence of rheumatoid arthritis (RA) symptoms but the presence of biomarkers, experts argue that early treatment with disease-modifying antirheumatic drugs (DMARDs) could prevent irreversible joint damage. This condition is referred to as pre-RA, but even the definition of that term is debated.

Early treatment, advanced therapies, and treat-to-target strategies have been clinically meaningful in RA patients.[1] These approaches, however, occur only after inflammatory arthritis manifests, and patients can no longer return to their pre-RA symptoms. Therefore, researchers have trained their sights on prevention.

Additionally, delays in diagnosis, the rising prices of drugs, and hampered access to rheumatologists further underscore the immediate need for preventive approaches.

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Various studies have pointed to a period of development in RA called “pre-RA” that is marked by antibody abnormalities or the presence of biomarkers sans clinical symptoms. 

“This was a major debate at the American College of Rheumatology's 2022 meeting," said Dr. Anita Chandrasekaran. "There is no clear definition for pre-RA, but it could be defined as those who have positive markers for RA (ie, positive rheumatoid factor and/or anti-CCP) or those who have joint pain with abnormal ultrasound findings, but may not have positive markers."

In patients who have positive markers, not all progress to clinical RA, and what leads to that progression is unclear, according to Dr. Chandrasekaran.

Even though a clear definition of the term pre-RA may be lacking, specialists do treat it.

“Treating preclinical rheumatoid arthritis involves intervening at an early stage of the disease before symptoms like joint pain and swelling appear. This approach is based on the understanding that joint damage can occur even in the absence of noticeable symptoms,” said Dr. David Ozeri.

“Studies have shown that early treatment of RA, including during the preclinical phase, can lead to better long-term outcomes. It can help reduce joint inflammation, control disease activity, and prevent or minimize irreversible joint damage. Early treatment also increases the likelihood of achieving remission or low disease activity, which improves quality of life for patients,” he added.

"Treatment strategies for preclinical RA may involve DMARDs such as methotrexate or targeted biologic therapies."

David Ozeri, MD, FACP, FACR

"These medications work to suppress inflammation and modify the underlying disease process, aiming to prevent or delay the onset of symptomatic RA and its associated complications,” he said.

Dr. Chandrasekaran also focuses on lifestyle interventions in these patients. "In those who have joint pain or intermittent swelling, I do consider early treatment, which may not prevent disease, but may delay onset of full-blown clinical RA,” she added.

"I tend to recommend lifestyle changes for those with positive markers, but no significant joint pain, such as a healthy diet, exercise, and smoking cessation."

Anita Chandrasekaran, MD, MPH

Related: Unraveling the psychological effects of arthritis

Controversy #2: Using dual biologics to treat PsA

Dual biologics target different pathways—ostensibly boosting efficacy—but unknowns, concerns over safety, and lack of evidence make the practice controversial.

Novel treatments of inflammatory arthropathies have improved clinical outcomes in many patients, yet there remains a contingent of patients who are refractory.

Dual-biologic therapy targeting different inflammatory pathways could be effective in treating inflammatory diseases like psoriatic arthritis (PsA) and RA that have complex and heterogeneous pathology, according to the authors of a review published in Rambam Maimonides Medical Journal.[2] 

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To date, several randomized controlled trials have assessed the safety and efficacy of dual-biologic treatment of RA, but the results have been mixed, which has raised safety concerns. 

Unlike with RA, there are no published clinical trials on dual-biologic treatment in PsA, and safety signals couldn’t be inferred from case reports or retrospective case series.  

Analysis of one case series of successful use of dual-biologic therapy in PsA found that IL-12/23i (ustekinumab)+TNFi, IL-23i (guselkumab)+TNFi, and IL-17i (secukinumab)+TNFi could be effective.

“To date, many questions remain unanswered regarding this novel field of therapy,” wrote the review article authors, “including the choice of the most efficacious anti-cytokine biologics, along with the most appropriate timing, sequence, frequency, and duration of treatment."

A potential strategy to decrease adverse events,” they suggested, “would be to use a lower dose of each therapy and consider asynchronous use of biologics with a loading dose of one drug followed by a sequential administration of another drug.” 

In addition, they added, “Along the rapidly evolving field of [immune-mediated disease] treatment, dual therapy may constitute an efficacious and safe add-on treatment to biologic therapy, but properly conducted clinical investigations are needed. In the meantime, dual biologic therapy used by physicians’ discretion requires close monitoring of patients with an emphasis on the safety profile."

Dr. Chandrasekaran warned that dual-biologic therapy may not be for every patient.

"The risk of infection certainly increases with dual-biologic therapy, so I would reserve this treatment strategy for younger patients with fewer comorbidities."

Anita Chandrasekaran, MD, MPH

However, she also said that it's not uncommon for patients with psoriasis or psoriatic arthritis to experience treatment failure with two or more biologics in the clinical setting, "and in patients who have tried multiple biologics, either on their own or in combination with a standard DMARD, this is a reasonable option."

Dr. Ozeri also stressed a personalized approach to deploying dual therapy.

"The potential benefits of dual-biologic therapy in psoriatic arthritis include enhanced disease control, treatment of refractory disease, and a personalized approach."

David Ozeri, MD, FACP, FACR

"However, this treatment approach is still being researched, and the use of multiple biologic medications simultaneously carries potential risks, including increased immunosuppression and the potential for adverse effects or drug interactions,” he said.

“The decision to pursue dual-biologic therapy in psoriatic arthritis should be made in consultation with a rheumatologist or healthcare provider experienced in the management of psoriatic arthritis. They will consider individual patient factors, treatment goals, potential risks, and benefits to determine the most appropriate treatment approach for each patient,” he advised.

Related: What can precision medicine do for rheumatology?

Controversy #3: Risks vs benefits of AI in rheumatology

Large-language models are rapidly taking hold in medicine and many argue they can enrich patient care, but they come with liability risks.

Large-language models such as AI chatbots/GPT can increase access to information, help with patient education, and support decision-making, said Dr. Ozeri. Limitations include lack of personalization, clinical experience, and emotional connection. The use of large-language models in healthcare is also fraught with ethical and legal concerns. 

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“Liability is an important consideration when using large-language models or AI chatbots in rheumatology or any other medical field," he said.

"While AI technologies can provide valuable information and support, they do not replace the responsibility and accountability of healthcare professionals."

David Ozeri, MD, FACP, FACR

“Liability issues can arise if there are errors, inaccuracies, or adverse outcomes resulting from the use of AI chatbots. Determining liability may involve assessing factors such as the design and development of the AI system, the training and deployment of the model, the communication of limitations and disclaimers to users, and the involvement of human healthcare professionals in the decision-making process,” he said.

“To mitigate liability risks, it is crucial to ensure that AI chatbots in rheumatology comply with applicable regulations and guidelines. Transparency in the capabilities and limitations of the system, clear communication of the boundaries of its advice, and the presence of human oversight are essential. Collaborating with legal experts and following best practices in the development and deployment of AI technologies can help minimize liability concerns,” he noted.

“Ultimately, liability for the use of AI chatbots in rheumatology or any medical context is a complex legal and ethical issue that requires careful consideration, adherence to regulations, and ongoing evaluation of the technology's performance and impact,” Dr. Ozeri reflected.

Dr. Chandrasekaran wonders about the veracity of findings but sees promise in large-language models.

"As a clinician, I would be worried about these large-language models providing false information, and what actually happens to the data inputted into these models."

Anita Chandrasekaran, MD, MPH

"On the other hand, I think it may be a future way for patients to receive more education about their diagnoses and management options outside of visits with their physicians, which will improve health literacy,” she added.

Related: Is AI-driven drug discovery the next big thing? Not quite yet

Controversy #4: Winding down DMARD therapy in RA patients with sustained remission

Although some patients in remission from RA relapse after tapering or discontinuing DMARDs, some don’t, making this treatment strategy a personal decision undertaken with a rheumatologist.

Enhanced treatment strategies and higher rates of remission in RA have caused researchers to shift their interests to the potential to achieve sustained remission. In the Rheumatoid Arthritis in Ongoing Remission (RETRO) study, German researchers examined the effects of tapering or stopping DMARDs in patients in sustained remission.[3]

In the phase 3 trial (n=316), investigators randomized 303 patients with DAS28-ESR remission (ie, >6 months) who were taking stable conventional synthetic or biologic DMARD treatment into three groups: (1) continuation on 100% DMARD dose (CONT); (2) tapering to 50% of the DMARD dose (TAP); (3) 50% tapering followed by DMARD withdrawal (STOP). The number of patients who continued in remission at 1 year was 81.2% in the CONT arm, 58.6% in the TAP arm, and 43.3% in the STOP arm. Predictors for flare-ups were female sex, longer disease duration, RF/ACPA positivity, and higher DAS-28 scores at baseline.

Dr. Chandrasekaran reflected on the study results.

“Remission is typically defined as no tender or swollen joints, and normal inflammatory markers (ESR and CRP)," she said.

"The study did demonstrate increased disease lapses with DMARD tapering, but a good proportion of patients stayed in remission despite tapering or stopping DMARDs."

Anita Chandrasekaran, MD, MPH

“I typically wait until my patients are symptom free for at least 1-2 years before tapering off medications slowly, and usually do so in a stepwise fashion; ie, initially steroids and/or NSAIDs, then biologics, then finally standard DMARDs (hydroxychloroquine, methotrexate),” she added.

Dr. Ozeri also takes a measured approach to reducing or withdrawing DMARDs in RA patients.

Any changes to the immunosuppressant regimen should be undertaken by the specialist and not the patient, Dr. Ozeri urged. The abrupt cessation or reduction of DMARDs without medical supervision and guidance can exacerbate symptoms and result in disease flares.

“The decision to adjust immunosuppressive medications depends on several factors, including the individual's disease activity, treatment response, and overall health status, and the specific medications being used,” he said.

“In general,” he added, “the goal of RA treatment is to achieve disease control and minimize symptoms while minimizing medication side effects."

"If a patient with RA has achieved sustained disease remission or low disease activity for an extended period, their healthcare provider may consider reducing the dosage or discontinuing certain immunosuppressive medications."

David Ozeri, MD, FACP, FACR

He noted, “The process of reducing or withdrawing immunosuppression is typically gradual and carefully monitored. It may involve stepwise tapering of medications, regular monitoring of disease activity and inflammatory markers, and assessing the patient's overall health status. The healthcare provider will assess the risk-benefit ratio, considering factors such as the likelihood of disease flare-ups, the impact on joint damage, and the potential for medication-related adverse effects.”

Read Next: Ankylosing spondylitis and RA: Possible comorbidities?

Controversy #5: The interplay between long COVID and autoimmune disease 

Symptoms of autoimmune disease and long COVID overlap, but whether autoimmune disease contributes to long COVID or whether immunosuppressants have a role in the treatment of long COVID is unknown. 

The focus of long COVID has been on the respiratory and cardiovascular symptoms, but the effects on autoimmune disease management and treatment is a rising concern.

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“Many of the symptoms of long COVID, or ‘long-hauler's syndrome,’ are symptoms commonly found in autoimmune diseases, such as post-exertional fatigue, myalgias/polyarthralgia, and neurocognitive dysfunction (brain fog),” said Dr. Chandrasekaran. 

"Many of these patients end up in rheumatology offices, given concern for autoimmune disease, and in fact, there is a question if long COVID is related to immune dysfunction, although the pathophysiology is still unknown."

Anita Chandrasekaran, MD, MPH

"It is also unknown whether autoimmune patients are more likely to develop long COVID than those without autoimmune disease at baseline. Certainly, some patients with autoimmune disease can have a flare of their disease after developing COVID-19. At this time, there is no role for immunosuppression in the treatment of long COVID, but if this changes in the future, rheumatologists will have a crucial role to play in managing these patients,” she remarked.

Dr. Ozeri explained that long COVID can trigger or exacerbate autoimmune disease flares in individuals who already have pre-existing autoimmune conditions.

"The persistent inflammation and immune dysregulation associated with long COVID can lead to increased disease activity, requiring adjustments to the treatment plan."

David Ozeri, MD, FACP, FACR

There is also a concern that immunosuppressants used to treat rheumatic disease can increase the risk of long COVID.

“Many autoimmune disease treatments involve immunosuppressive medications, which can potentially increase the risk of severe COVID-19 infection. Individuals with autoimmune diseases and long COVID need careful evaluation to balance the management of autoimmune disease activity while considering the risks associated with immunosuppression and potential susceptibility to viral infections,” cautioned  Dr. Ozeri.

Related: Invisible symptom: The heavy toll of fatigue in inflammatory arthritis

The takeaway

Despite rapid advances in the field of rheumatology, there is still much to learn. After all, rheumatology is still a relatively young subspecialty, and the lack of protocol-defined guidelines for treatments results in differences in practice among rheumatologists.

Moreover, rheumatology patients often experience chronic symptoms that are challenging to treat and clinical response to treatment can vary widely. All of these factors predispose the field to controversy, debate, and discussion.

Read Next: Wearable activity trackers show promise in rheumatic disease


  1. Greenblatt HK, Kim HA, Bettner LF, et al. Preclinical rheumatoid arthritis and rheumatoid arthritis prevention. Current Opinion in Rheumatology. 2020;32(3):289–296.

  2. Furer V, Elkayam O. Dual biologic therapy in patients with rheumatoid arthritis and psoriatic arthritis. Rambam Maimonides Medical Journal. 2023;14(2):e0007. 

  3. Hagen M, Tascilar K, Reiser M, et al. OP0318 treatment tapering and withdrawal in rheumatoid arthritis with stable remission - final analysis of the RETRO study. Annals of the Rheumatic Diseases. 2021;80(Suppl 1):194–195.