503 - Injectable Methylprednisolone, MRAs to Prevent A-Fib, Let’s Connect

A Question From a Colleague

1)  Clinical Uses of Injectable Methylprednisolone (Depo-Medrol)

Question: 

“I’m hoping you might provide Take 3 readers an update on the clinical uses of injectable methylprednisolone and the evidence behind them?  I’m concerned about the use of this medication at higher doses that aren’t evidence-based.”

Answer: 

Methylprednisolone, prednisolone, prednisone, and triamcinolone are considered “intermediate acting” systemic glucocorticoids with a duration of action of 12-36 hours and relative milligram equivalence.   While injectable (intramuscular/IM or intra-articular) steroids are commonly used for a myriad of medical conditions, according to Lexicomp the evidence to support an optimal dose and duration are lacking for most indications.  Therefore, “recommendations provided are general guidelines only and primarily based on expert opinion. In general, glucocorticoid dosing should be individualized and the minimum effective dose/duration should be used.” 

Methylprednisolone has multiple FDA approved indications for IM administration “when oral therapy is not feasible.”  Notable indications (there are many more) in the primary care setting include:

·         Allergic States:  When control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment, including asthma, atopic dermatitis, contact dermatitis, drug hypersensitivity reactions, seasonal or perennial allergic rhinitis

·         Dermatologic Diseases: Bullous dermatitis herpetiformis, exfoliative dermatitis

·         Gastrointestinal Diseases: To tide the patient over a critical period of the disease in regional enteritis (systemic therapy) and ulcerative colitis

·         Hematologic Disorders: Acquired (autoimmune) hemolytic anemia, select cases of secondary thrombocytopenia.

·         Ophthalmic Diseases: temporal arteritis

·         Rheumatic Disorders: As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis; psoriatic arthritis; rheumatoid arthritis,

For Intra-articular or soft tissue administration:

·         Indicated as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, synovitis of osteoarthritis.

For Intralesional Administration:

·         Indicated for intralesional use in alopecia areata, keloids, lichen planus, lichen simplex chronicus (neurodermatitis) and psoriatic plaques; necrobiosis lipoidica diabeticorum.

As noted above, for any indication the minimum effective dose and duration of treatment should be prioritized given potential side effects.  In my reading, common indications for higher doses might include:  

·         Large joint injections (up to 80 mg)

·         Asthma exacerbations (up to 120 mg)

·         Severe contact dermatitis (up to 80 mg)

High dose use (or use in general) should be avoided for chronic conditions and non-specific complaints, including seasonal allergies, non-specific chronic “arthritis,” fibromyalgia, chronic back pain.

Mark’s Comments:

Systemic steroids are a class of medications that are ripe for overuse, as they can provide temporary relief for many conditions, but can also come with significant short-term and long-term side effects.  Since they’ve been around a long time, much of the data that led to their approval for so many indications is quite old.  For example, a systematic review on the data on use for seasonal allergic rhinitis showed that most studies cited were done in the 1960’s, and there were significant methodological concerns with all of them (2^nd reference). 

Another example for the risk of overuse is the common use of systemic steroids (both oral and IM) for acute upper respiratory tract infections, a practice for which there is no clear medical justification.  A wonderful cohort study of almost 10 million patients treated for acute URI  (3^rd reference) showed that 11.8% were prescribed systemic steroids and revealed profound regional and specialty variation when it comes to this practice, with a high of 23% for patients in the state of Louisiana and 17% for otolaryngologists.  When it comes to prescribing these medications, prescribe wisely.

References:

·         FDA Package Insert:  Link

·         Bayoumy A, et al.  Intramuscular corticosteroid injections in seasonal allergic rhinitis: A systematic review. Laryngoscope Investig Otolaryngol.  2021 Oct; 6(5): 911–923.  Link

·         Lin K, et al.  Prescribing systemic steroids for acute respiratory tract infections in United States outpatient settings: A nationwide population-based cohort study. PLoS Med. 2020 Mar; 17(3): e1003058 Link

From the Literature

2) Mineralocorticoid Antagonists to Prevent A-Fib

Mineralocorticoid antagonists (MRAs; spironolactone, eplerenone, finerenone, and canrenone) are increasingly recommended for hypertension and heart failure. The authors of a systematic review in the American Journal of Cardiology wanted to know if the use of these agents protected against atrial fibrillation, the most common arrythmia. They included studies of MRAs vs. other medications or placebo that used development of atrial fibrillation as an outcome. The indications for the MRAs varied. The authors performed a reasonably comprehensive search. They included only randomized controlled trials, critically appraised the included studies, and examined the meta-analysis results for heterogeneity.

Out of 7100 studies found, only ten studies (N = 11,356) met criteria for inclusion, and these were all found to be at low risk of bias. Overall, there was a reduced risk of atrial fibrillation in the MRA groups (relative risk (RR) 0.77, 95% confidence interval (CI) 0.65 to 0.91, I²=40%). The list of indications for MRAs included heart failure of various degrees and causes, atrial fibrillation (the outcome, therefore, was recurrence of atrial fibrillation), and cerebral edema. Across the range of heart failure, MRAs worked best for heart failure (HF) with reduced ejection fraction (EF; RR 0.61,95% CI 0.42 to 0.89), reasonably well for no HF (RR 0.74, 95% CI 0.65 to 0.84), and not at all for HF with preserved EF (RR 1.12, 95% CI 0.83 to 1.51). There were no safety outcomes reported.

The authors conclude that MRAs are effective in preventing atrial fibrillation when used for a variety of indications.

John’s Comments:

This type of study is a bit frustrating. It’s reasonably well-structured as a systematic review, and I think there is signal here, but it misses some important points, like clearly defining the circumstances in which clinicians would look to start an MRA. The lack of safety data is also troublesome. Because of these issues, this is not really practice changing yet, but does help me feel better about using these agents for the several other indications (HF, HTN, etc.) that have been identified over the last few years.

Reference:

·         Fatima K, Asad D, Shaikh N, et al. A Systematic Review and Meta-Analysis on Effectiveness of Mineralocorticoid Receptor Antagonists in Reducing the Risk of Atrial Fibrillation. Am J Cardiol. 2023;199:85-91. Link

From PeerRxMed ( www.PeerRxMed.org )

3)  Let’s Connect

“Loneliness is far more than just a bad feeling—it harms both individual and societal health.”  US Surgeon General Vivek Murthy, MD, MBA

How connected do you feel to those around you, particularly at work?  Do you often feel like a “parallel private corporation” rather than a “partner” with your clinical colleagues, too busy to even think about creating any meaningful relationships?

If that at all describes you, you are not alone … but you likely are feeling lonely.  That’s according to the research by Shawn Achor and colleagues at BetterUp, who found that as a profession, we physicians tend to be a lonely group, right up there with our legal colleagues.  In their words: “Graduate degree holders … reported higher levels of loneliness and less workplace support than respondents who had only completed undergraduate or high school degrees.  Professional degrees (law and medical degrees) were the loneliest by far, scoring 25% lonelier than bachelor’s degrees, and 20% lonelier than PhDs.”   

It gets worse.  More recent surveys indicate that loneliness among adults in the US has reached epidemic proportions with approximately half of those surveyed experiencing significant  loneliness.  Paradoxically, young adults, who statistically are the most “connected” through social media, were experiencing some of the highest rates.  Yet less than 20% of those who often or always felt lonely or isolated recognized it as a major problem.

As a response, in May of 2023, at the same time that the U.S. Department of Health and Human Services (HHS) was declaring the end of the COVID-19 emergency, the US Surgeon General’s office under the leadership of Vivek Murthy, MD, published an advisory titled “Our Epidemic of Loneliness and Isolation.”  The advisory summarized the unprecedented levels of loneliness, disconnection, and isolation being experienced within our communities, and laid out a roadmap forward.

The Surgeon General’s advisory indicated that loneliness is associated with a greater risk of cardiovascular disease, dementia, stroke, depression, anxiety, and premature death.  The sobering data indicate the mortality impact of being socially disconnected is estimated to be similar to that caused by smoking up to 15 cigarettes a day, and even greater than that associated with obesity and physical inactivity.

Dr. Murthy provides some personal encouragement in his introductory letter for the report:  “Loneliness and isolation represent profound threats to our health and well-being.  Each of us can start now, in our own lives, by strengthening our connections and relationships. Our individual relationships are an untapped resource—a source of healing hiding in plain sight. They can help us live healthier, more productive, and more fulfilled lives.  Answer that phone call from a friend.  Make time to share a meal. Listen without the distraction of your phone.  Perform an act of service. Express yourself authentically.  The keys to human connection are simple, but extraordinarily powerful.”

Or, he could have simply said, “Find a buddy and share the journey together, and encourage others to do the same.”  The data are quite clear and very concerning.  No one should care alone ….

______________

Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org