Abstract and Introduction
Background/Objective: Corticosteroids have long been used to effectively treat rheumatic disorders, but adverse effects associated with extended-duration regimens generate disagreement among clinicians regarding optimal tapering strategies. The objective of this systematic review was to assess clinical outcomes of differing tapering regimens after corticosteroid monotherapy in adults with rheumatic disorders.
Methods: A systematic review of Medline/PubMed, Embase, Cochrane, International Pharmaceutical Abstracts, Web of Science, Scopus, Global Index Medicus, American College of Rheumatology, gray literature, and reference lists up to June 27, 2018, was conducted by 2 authors. Randomized controlled trials, case-control studies, and prospective observational studies comparing at least 2 tapering strategies of medium- to high-dose (>7.5 mg but ≤100 mg oral prednisone equivalent daily), extended-duration (≥10 days) corticosteroids were included if they reported at least 1 efficacy and 1 adverse effect parameter.
Results: Two studies met criteria for the review, which included 62 patients. One study examined a prednisolone versus a modified release prednisone taper for giant cell arteritis and suggested 80% (n = 4) and 85.7% (n = 6) remission rates, respectively, at 26 weeks. The other study examined a methylprednisolone versus a prednisone taper for polymyalgia rheumatica and reported 100% and 89% remission rates, respectively, at 26 weeks. Adverse effects reported between the 2 studies included sleep, hyperglycemia, infection, and fractures. However, the studies were not powered to detect differences in these outcomes.
Conclusions: There is no high-level evidence to guide tapering until discontinuation after extended courses of medium- to high-dose treatment regimens, as current guidelines rely heavily on expert opinion and small case series with a trial-and-error approach. This review supports the need for additional research to shift tapering recommendations to a more evidence-based practice.
The first synthesized corticosteroid known as compound E, now known as cortisone, was administered to a patient with rheumatoid arthritis in 1948. The patient was free of pain within a few days of treatment, so the cortisone was continued. After about a month of therapy, the patient was admitted to a psychiatric ward after experiencing a variety of central nervous system adverse effects such as depression and psychosis from the cortisone therapy. The cortisone therapy was stopped, but the patient died several years later due to complications from adrenocorticotropic hormone therapy. This case illustrates the marked clinical improvement that can occur within a few days of receiving a corticosteroid and the devastating adverse effects that can occur with prolonged therapy.
Corticosteroids exhibit diverse genomic and nongenomic mechanisms of action on immune cells, tissue, and organs that gives them efficacy for a wide range of indications including endocrine disorders, rheumatic disorders, collagen diseases, dermatologic diseases, allergic states, ophthalmic disease, neoplastic disease, certain edematous states, and nervous system disorders. The diverse mechanisms of action that allow for the treatment of these disorders also accounts for the diverse adverse effect profile of corticosteroids. Every organ system in the body may be negatively impacted by long-term corticosteroid therapy: skin (eg, thinning, bruising), muscle (eg, wasting, cramping), skeletal (eg, osteoporosis), nervous (eg, psychiatric and sleep disturbances), circulatory (eg, hypertension), lymphatic (eg, lymphedema), respiratory (eg, infection), endocrine (eg, diabetes), reproductive (eg, fertility), urinary/excretory (eg, infection, glycosuria), and digestive (eg, ulcers). These adverse effects are dose and duration dependent. Although dose and duration thresholds are not well-established, the more consequential adverse effects of corticosteroids usually occur with supraphysiologic doses administered for more than 7 to 10 days. A physiologic or low dose of corticosteroid is defined as a prednisone equivalent dose 7.5 mg or less daily. Supraphysiologic doses are defined as medium dose greater than 7.5 mg but 30 mg or less daily, high dose greater than 30 mg but 100 mg or less daily, very high dose greater than 100 mg daily, and pulse therapy 250 mg or greater a day for at least 1 day.
The corticosteroid regimens for patients with inflammatory disorders such as rheumatic diseases typically use higher initial doses to arrest or reverse the disease process and achieve symptomatic control. When the latter is achieved, a tapering regimen is implemented that decreases the dose of corticosteroid as rapidly as possible while maintaining disease control to minimize corticosteroid-related adverse effects. The objective of this systematic review was to assess clinical outcomes (efficacy and adverse effects) of differing tapering regimens after medium- to high-dose (>7.5 mg but ≤100 mg oral prednisone equivalent daily), extended-duration (at least 10 days) corticosteroid therapy in adults with rheumatic disorders. The focus was on randomized controlled trials (RCTs), case-control studies, and prospective observational studies that compared at least 2 tapering regimens of medium- to high-dose, extended-duration corticosteroid monotherapy in adults.
J Clin Rheumatol. 2020;26(2):41-47. © 2020 Lippincott Williams & Wilkins