Idiopathic Pulmonary Fibrosis (IPF)


The composition of Sterapred® is prednisone, a glucocorticoid.1 The Sterapred brand name has been discontinued in the US; the brand names commonly used in the US are Deltasone®, Prednisone Intensol, and Rayos®.2 Glucocorticoids are naturally occurring or synthetic adrenocortical steroids that are readily absorbed in the gastrointestinal tract. Prednisone is an odorless, crystalline powder with a white to off-white color. It shows mild solubility in water, alcohol, chloroform, dioxane, and methanol.1

The function of prednisone is to provide relief from inflammation in the body. It is useful for many conditions, such as inflammatory swellings, severe allergies, arthritis, asthma, adrenal diseases, endocrine disorders, eye or vision problems, stomach and bowel diseases, blood and bone marrow diseases, lupus and other skin diseases, kidney conditions, ulcerative colitis, and multiple sclerosis flare-ups.3

Sterapred is available in 1 mg, 2 mg, and 5 mg tablets for oral administration in idiopathic pulmonary fibrosis (IPF). The dosage of prednisone is individualized based on disease severity and patient response.3

Sterapred
Prednisone is a synthetic glucocorticoid drug that is particularly effective as an immunosuppressant, and affects virtually all of the immune system.
Credit: Getty Images

Sterapred Mechanism of Action

Prednisone is a synthetic glucocorticoid with anti-inflammatory and immunomodulating actions. Corticosteroids bind to the glucocorticoid receptor, causing inhibition of proinflammatory signals and activation of anti-inflammatory signals. The half-life of prednisone is 2 to 3 hours; hence, it has a short duration of action. Following cell surface receptor attachment and entry into the cell, prednisone enters the nucleus and binds and activates specific nuclear receptors, leading to altered gene expression and inhibition of proinflammatory cytokine production.4 Decreases in eosinophils and lymphocytes are also noted, whereas erythropoiesis and formation of polymorphonuclear leukocytes are activated. Inflammatory mechanisms are also inhibited, such as fibrin deposition, dilation of capillaries, edema, leukocyte migration and phagocytosis, and the late stages of wound healing including proliferation of capillaries, collagen deposition, and cicatrization.3

Absorption

When taken with food, prednisone is released from Sterapred approximately 4 hours after ingestion. It leads to a delay in the time of peak plasma concentration (Tmax).3 

Metabolism 

Prednisone shows a complete conversion to the active metabolite, prednisolone, which is further metabolized predominantly in the liver and excreted in the urine as sulfate and glucuronide conjugates.3 

Patients with IPF Treated With Prednisone Monotherapy

There have been no randomized controlled trials conducted with prednisone monotherapy.5,6 Retrospective uncontrolled studies have documented no benefits in survival, but they have found that a few cases treated with prednisone monotherapy showed improvements in lung function.7,8 Controlled data, however, have seen no benefits in survival.9 Morbidity is significant with long-term prednisone therapy.7

It is thus recommended that patients with IPF should not be treated with prednisone monotherapy to prevent treatment-related morbidity, despite the potential improvement in lung function noted in a few cases.10

Patients with IPF Treated With Combination Prednisone and Immunomodulator Therapy

A retrospective study demonstrated marked benefits of treatment with azathioprine plus prednisone in a small series of cases.11 A small randomized trial of prednisone alone compared to prednisone plus azathioprine exhibited survival benefits with combination therapy.12 Prednisone plus cyclophosphamide were also compared with prednisone alone, and survival benefits were noted with the addition of cyclophosphamide.13  However, the trial results are confounded because the included cases do not meet the recent diagnostic criteria for IPF. Two retrospective, controlled studies of cyclophosphamide have been found in the literature. The first one compared prednisone and cyclophosphamide combination therapy to no therapy in 164 patients, and there were no differences in survival.14 The second compared prednisone plus cyclophosphamide therapy to prednisone alone in 82 cases, and benefits in survival were seen with combination therapy.15

Sterapred as Part of Triple Combination Therapy for IPF

Combination therapy for IPF includes N-acetylcysteine (NAC), Imuran® (azathioprine), and prednisone. The safety and efficacy of triple combination therapy are unknown. A double-blind, randomized, placebo-controlled trial was conducted in patients with IPF. They had mild to moderate lung function impairment and were administered NAC, Imuran, and prednisone in a 1:1:1 ratio combination. The 60-week treatment outcome involved longitudinal measurement of forced vital capacity. The trial showed that the treatment preserved lung function better than 2-drug regimens. The efficacy of the triple combination therapy is inconclusive, as the trial did not include any placebos for prednisone or Imuran. The international guidelines differ in terms of their recommendations for triple combination therapy. A study termed PANTHER-IPF (Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis) evaluated the response of triple-drug therapy in patients with IPF. It compared the matched placebos for patients with mild to moderate impairment in pulmonary function. Drug therapy was stopped according to a prespecified interim assessment by the data and safety monitoring board. The placebo and NAC-only groups continued to recruit according to the prespecified duration of 60 weeks.16

The American Thoracic Society has no current recommendations for the use of combination therapy of NAC, azathioprine, and prednisone in IPF cases. It becomes imperative to find a close case-by-case approach between the patient and their doctor to assess the potential benefits and harms of the treatment.17

Although most IPF cases should not be given a combination of corticosteroid, azathioprine, and NAC therapy, this therapy can be used in a minority of cases. It is a weak recommendation because of low-quality evidence.10

Warnings, Precautions, and Adverse Reactions

Contraindications of prednisone tablets are systemic fungal infections and known hypersensitivity to components.1 The most common adverse reactions of prednisone are changes in glucose tolerance, increased blood pressure, fluid retention, mood and behavioral changes, increased appetite, and weight gain.3

Precautions Prior to Taking Prednisone

Patients taking immunosuppressive doses of prednisone must be cautioned to avoid exposure to diseases such as measles or chickenpox. Patients are also advised that in cases of exposure, medical advice must be sought without delay.1

Drug-to-Drug Interactions

Drugs that induce hepatic enzymes like phenobarbital, phenytoin, and rifampin can cause rapid clearance of prednisone and thus require an increased prednisone dose to attain the desired response. Drugs like troleandomycin and ketoconazole can inhibit the metabolism of prednisone and reduce its clearance. Thus, titration of the prednisone dose must be done to prevent steroid toxicity. An increased clearance of prednisone is seen with chronic high-dose aspirin doses. This can cause reduced serum levels of salicylate or increase the risk of salicylate toxicity when prednisone is withdrawn. Aspirin should be used with caution in combination with prednisone in hypoprothrombinemia cases. The effects of prednisone on oral anticoagulants are variable. Reports of both increased and decreased effects of anticoagulants in conjunction with prednisone are documented. Hence, close monitoring of coagulation indices should be performed for optimization of the desired anticoagulant effect.1

References

  1. ​​Sterapred. Package insert. Merz Pharmaceuticals. Accessed August 12, 2021.
  2. Sterapred (oral). Drugs.com. Updated March 19, 2021. Accessed August 12, 2021.
  3. Rayos. Package insert. Horizon Pharma USA, Inc. Accessed August 12, 2021.
  4. Prednisone. National Center for Biotechnology Information. Accessed August 12, 2021. 
  5. Davies HR, Richeldi L, Walters EH. Immunomodulatory agents for idiopathic pulmonary fibrosis. Cochrane Database Syst Rev. 2003;(3):CD003134. doi:10.1002/14651858.CD003134
  6. Richeldi L, Davies HR, Ferrara G, Franco F. Corticosteroids for idiopathic pulmonary fibrosis. Cochrane Database Syst Rev. 2003;(3):CD002880. doi:10.1002/14651858.CD002880
  7. Gay SE, Kazerooni EA, Toews GB, et al. Idiopathic pulmonary fibrosis: predicting response to therapy and survival. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1063-1072. doi:10.1164/ajrccm.157.4.9703022
  8. Flaherty KR, Toews GB, Lynch JP III, et al. Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival. Am J Med. 2001;110(4):278-282. doi:10.1016/s0002-9343(00)00711-7
  9. Nagai S, Kitaichi M, Hamada K, et al. Hospital-based historical cohort study of 234 histologically proven Japanese patients with IPF. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16(2):209-214.
  10. Raghu G, Collard HR, Egan JJ, et al.; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788-824. doi:10.1164/rccm.2009-040GL
  11. ​​Winterbauer RH, Hammar SP, Hallman KO, et al. Diffuse interstitial pneumonitis: clinicopathologic correlations in 20 patients treated with prednisone/azathioprine. Am J Med. 1978;65(4):661-672. doi:10.1016/0002-9343(78)90855-0
  12. Raghu G, Depaso WJ, Cain K, et al. Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial. Am Rev Respir Dis. 1991;144(2):291-296. doi:10.1164/ajrccm/144.2.291
  13. Johnson MA, Kwan S, Snell NJ, Nunn AJ, Darbyshire JH, Turner-Warwick M. Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis. Thorax. 1989;44(4):280-288. doi:10.1136/thx.44.4.280
  14. Collard HR, Ryu JH, Douglas WW, et al. Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis. Chest. 2004;125(6):2169-2174. doi:10.1378/chest.125.6.2169
  15. Pereira CA, Malheiros T, Coletta EM, et al. Survival in idiopathic pulmonary fibrosis-cytotoxic agents compared to corticosteroids. Respir Med. 2006;100(2):340-347. doi:10.1016/j.rmed.2005.05.008
  16. The Idiopathic Pulmonary Fibrosis Clinical Research Network. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012;366(21):1968-1977. doi:10.1056/NEJMoa1113354
  17. Corticosteroids to treat PF. Pulmonary Fibrosis News. Accessed Aug 12, 2021.

Reviewed by Debjyoti Talukdar, MD, on 8/12/2021.