‘Our friend and our enemy’: Rheumatologists continue to grapple with steroids
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The movement away from long-term steroid use has reached all corners of rheumatology, and for good reason: Extended use of glucocorticoids can be associated with a raft of adverse outcomes.
However, complete elimination of steroids will likely never occur, as they solve certain problems that few other drugs can.
“Steroids are our friend and our enemy,” Joan T. Merrill, MD, a member of the Arthritis & Clinical Immunology Program at the Oklahoma Medical Research Foundation, and OMRF professor of medicine at the University of Oklahoma Health Sciences Center, told Healio. “They can get us out of trouble rapidly and save lives, but long-term use is associated with unacceptable medical problems, organ damage and premature death.”
Evidence of this is seen in several guidelines and recommendations, including those from the American College of Rheumatology for rheumatoid arthritis and juvenile idiopathic arthritis. Steroids are recommended in specific situations, but with a host of caveats and suggestions for dose reduction and tapering.
Richard Furie, MD, chief of the division of rheumatology at Northwell Health and professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, in New York, couched his feelings for steroids in terms of “love/hate.”
“From the first time they were used in 1948, they have been transformative for patients with so many of our inflammatory diseases,” he said. “But their indications list pages and pages of toxicities and damages that they can cause.”
With so many possible adverse effects, it raises the question of why even continue using them at all.
One reason is that they act quickly. They have the capacity to pull patients from the brink during disease flares or unexpected extreme complications. However, this is not the only reason they remain an integral component of rheumatology care.
“There are some diseases where steroids are the only option,” Merrill said. “And the reason for this is that the better options that probably exist have not yet been identified.”
Part of the reason for this is that many diseases under the rheumatology umbrella are rare, with few patients available for studies, which in turn means fewer research dollars are directed to the specialty compared with more high-profile area like oncology or cardiology.
However, the rheumatology research community continues to explore steroid-sparing approaches. Until alternatives are found to be effective and available for every disease and condition, rheumatologists will be left to continue the uneasy relationship with these drugs.
Turning the ‘pyramid upside-down’
In 2021, the ACR updated their RA guidelines to make steroid sparing something of a centerpiece. Published in Arthritis Care & Research by Fraenkel and colleagues, it was suggested that enough evidence had mounted to support a strong recommendation for the initiation of a conventional synthetic disease-modifying antirheumatic drug without prolonged glucocorticoids for DMARD-naïve patients with moderate-to-high disease activity.
Although steroids can bring a newly diagnosed patient under control quickly, and are often started with the intention of keeping them at low doses for short time, the decision by Fraenkel and colleagues was made at least in part because that is not always how things play out in real-world clinical situations.
Starting with a DMARD ensures that a patient will not end up on months and months of glucocorticoids simply because they are doing the job that another drug could be doing.
“There has been enough progress in some less rare diseases such as lupus, rheumatoid arthritis and others, to make it very possible to reduce or even eliminate the use of steroids for much or most of the time,” Merrill said.
In the 2019 update of the joint EULAR/European Renal Association/European Dialysis and Transplant Association recommendations for the management of lupus nephritis, published in the Annals of the Rheumatic Diseases, Fanouriakis and colleagues also highlighted the adverse impacts of long-term glucocorticoid therapy. They suggested that a lower starting dose of glucocorticoids — defined as 0.5mg/kg/day — may be as effective as a higher dose. They also made stipulations for reducing total intravenous prednisone doses to between 500 mg and 2,500 mg, and reducing doses over the course of 3 to 6 months.
“The positive of these updated guideline documents is that it is bringing awareness to the side effects of steroids, particularly the increased risk of cardiovascular disease,” Sangeeta Sule, MD, PhD, chief of the division of rheumatology at Children’s National Hospital, in Washington, D.C., and associate professor of pediatrics at the George Washington University School of Medicine and Health Sciences, said in an interview. “The negatives may be that physicians feel obligated to taper steroids more quickly than clinically appropriate for that individual patient.”
In 2022, the ACR released two updated documents for JIA, which are to serve as companion papers to a joint guideline from the ACR and the Arthritis Foundation in 2019. One paper deals with pharmacotherapies, while the other deals with non-pharmacologic interventions.
Lead author Karen Onel, MD, of the departments of pediatrics and rheumatology at the Hospital for Special Surgery, in New York, provided a statement on steroid sparing in a press release.
“For many years, treatment of JIA consisted of corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), physical therapy, bracing and surgery,” she said. “These guidelines stress the early use of conventional synthetic and biologic DMARDs and the avoidance of glucocorticoids and NSAIDs. In fact, for systemic JIA the guidelines suggest using biologic DMARDs as a first line. We have turned the pyramid upside down.”
With so many documents emerging and so much data supporting reduced glucocorticoid dosing across the board, it raises the question of why, and when, to even use the drugs.
Fast-acting relief
If there is one overwhelming reason to use steroids, it has to do with the rapid onset of action, according to Sule.
“Most of our immune suppressing medications, such as methotrexate or cyclophosphamide, take a few weeks to reach full efficacy,” she said. “Steroids work within hours. This fast onset of action is the only way to control significant, life-threating complications such as pulmonary hemorrhage from vasculitis, or kidney failure from lupus.”
The rapid onset of action also lends itself to a paradigm of early intervention that gives way to another therapeutic option.
“In children with less dramatic presentations, such as JIA, steroids can be used up front and tapered quickly,” Sule said.
According to Furie, the question of whether to reach for steroids depends on how quickly one needs to act.
“If someone comes in with lupus and they have a platelet count that is life-threatening, you can try an immunosuppressive, but if they have a fatal bleed, you need to start steroids right away or they are going to die,” he said.
The complications that can arise in adult patients certainly warrant steroid use on occasion. However, the issues are more complicated in pediatric patients with rheumatic and autoimmune diseases.
‘Huge problem for pediatric rheumatology’
As difficult as it is to study certain rheumatologic conditions in adult patients, it is even more difficult in children and adolescents, again in part because many of the diseases are rare.
“This is a huge problem for pediatric rheumatology,” Sule said.
Sule noted that SLE affects between 5,000 and 10,000 children in the United States.
“This means that an individual center may have few patients to conduct studies,” she added. “Collaborative research is the key for these diseases.”
Because of the small patient population and the small number of studies being conducted in other therapeutic options, children with SLE are often treated with steroids. However, Sule noted that steroids can be particularly toxic for children.
“The pediatric population has some unique steroid side effects to consider including growth disturbance and an increased risk of cataracts,” she said.
Furie stated that as much as 80% of the damage accrual in lupus is not from the disease itself, but from steroids, adding osteonecrosis to the complications described by Sule.
That said, childhood SLE and vasculitis often require steroids to bring inflammation under control quickly, according to Sule.
“These patients are often first diagnosed when they present to the hospital with end organ involvement, such as kidney failure from SLE,” she said. “Steroids are the only way to control the disease quickly to preserve organ function.”
It is with this in mind that Furie suggested that the best way forward for steroid use in rheumatology is to appeal to the art as much as the science of medicine.
“The goal now is to use the lowest dose, for the shortest duration, that we think will do the job,” he said.
Merrill underscored this point.
“The push to find ways to safely reduce or eliminate steroids in the appropriate clinical situations is right and important,” she said. “But this does not mean that we will never need them.”
References:
- Fanouriakis A, et al. Ann Rheum Dis. 2020; 10.1136/annrheumdis-2020-216924.
- Fraenkel L, et al. Arth Care & Res. 2021;doi: 10.1002/acr.24596.
- Onel KB, et al. Arth & Rheum. 2022;doi:10.1002/art.42037.
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