Low Dose 6-Metilprednisone Prophylaxis Effectively Prevents Acute Phase Reaction Symptoms


Patients receiving 6MP prophylaxis experienced significantly reduced incidence of arthromyalgia and Health Assessment Questionnaire worsening of 22% or increase of .25.

A low dose of 6-metilprednisone (6MP) prophylaxis was effective in preventing the most common symptoms of acute phase reaction when compared with paracetamol or placebo, according to data presented at the European Congress of Rheumatology (EULAR) 2023.1 In contrast to previous research, investigators found previous exposure to oral bisphosphonates, normal 25-hyrdroxyvitamin D3 (25[OH]D3) serum levels, or 25(OH)D3 supplementation did not impact the incidence of acute phase reaction.

Low Dose 6-Metilprednisone Prophylaxis Effectively Prevents Acute Phase Reaction Symptoms

Credit: Adobe Stock/Monstar Studio

Acute phase reaction is a transient flu-like syndrome which is commonly presented as symptoms of fever, chills, fatigue, malaise, and musculoskeletal, often occurring within 24 to 36 hours after intravenous bisphosphonates (IV-BPs) administration and is usually resolved within 2-3 days.2 Investigators noted that avoiding the syndrome may increase a patient’s compliance to treatment as well as reduce their discomfort.

The monocentric, randomized, open-label, parallel-group study analyzed the efficacy of a low dose of 6MP, paracetamol, or placebo in reducing the incidence of acute phase reaction. Investigators prospectively enrolled patients between March 2022 and December 2022. These patients were randomized to receive paracetamol 1000mg twice a day for 3 days, 6MP 4mg twice a day for 3 days, or placebo after IV-BPs (either zoledronate [ZOL] 5 mg or neridronate [NER] 100 mg).

Symptoms were rated on a scale of 0 (absence), 1 (mild), 2 (moderate), and 3 (severe). Arthromyalgia was categorized as myalgia, arthritis, chest pain, and arthralgia, and systemic symptoms included nausea, headache, fatigue, fever, and the Health Assessment Questionnaire (HAQ). Arthromyalgia, fever, and HAQ were evaluated at baseline and again at day 4. Acute phase reaction was defined as a worsening of >2 points in fever or arthromyalgia and/or a worsening of 22% or increase of .25 in the HAQ score.

Logistic regression analyzed protective and predictive factors for acute phase reaction occurrence, while comparisons were performed by T test and chi-square test.

A total of 95 patients were enrolled in the study, with a mean age standard deviation (SD) of 57 years and a mean body mass index (BMI) SD of 24.51. Most (69.5%) of patients were female, 70.5% were menopausal, 10.5% had previous exposure to oral bisphosphonates, and 14 patients were under chronic treatment with statins. The most common reasons for treatment with bisphosphonates were complex regional pain syndrome type 1 (78%, n = 74), osteoporosis (17%, n = 16), and Paget’s disease of bone (5%, n = 5).

Among patients, 29 received 6MP, 29 received paracetamol, and 37 were placed in the placebo cohort. The incidence rates of arthromyalgia and systemic symptoms in patients receiving ZOL were 46.7% and 60%, respectively. Incidence rates in the NER cohort were 38.8% and 21.4%, respectively. Patients receiving 6MP prophylaxis experienced significantly reduced incidence of arthromyalgia (P = .03) and HAQ worsening of 22% or increase of .25 (P = .01 and P = .05, respectively). However, it did not prevent then incidence of systemic symptoms (P = .23). Treatment with paracetamol or placebo did not change the incidence of systemic symptoms, arthromyalgia, or worsening of HAQ.

While the chronic use of statins prevented the incidence of arthromyalgia and worsening of HAQ (P = .029 and P = .015, respectively), it did not impact the systemic symptoms score. Further, previous oral bisphosphonates exposure was not shown to prevent acute phase reaction.

Protective variables for the incidence of arthromyalgia were older age (odds ratio [OR] 95% confidence interval [CI] 1.01 – 1.11, P = .02) and 6MP prophylaxis (OR 5.0, CI 1.79 – 2.97, P = .03). A higher BMI (OR 1.32, CI 1.07 – 1.65, P = .01) and treatment with ZOL (OR 31.6, CI 2.3 – 431.96, P = .01) were predictive factors for fever occurrence. Acute phase reaction was not prevented by previous exposure to oral bisphosphonates, 25(OH)D3 serum levels, 25(OH)D3 ongoing supplementation, or concomitant statins.


  1. R DI Taranto, C Crotti, A Amati, F Zucchi, et al. Is Prevention Better Than Cure? Data From a Monocentric Randomized Clinical Trial to Prevent Acute Phase Reaction Related to Intravenous Bisphosphonates. Paper presented at: European Congress of Rheumatology (EULAR) 2023. Milan, Italy. May 31 – June 3, 2023.
  2. Olson K, Van Poznak C. Significance and impact of bisphosphonate-induced acute phase responses. J Oncol Pharm Pract. 2007;13(4):223-229. doi:10.1177/1078155207080806
Related Videos
What Makes JAK Inhibitors Safe in Dermatology
Potential JAK Inhibitor Combination Regimens in Dermatology
Therapies in Development for Hidradenitis Suppurativa
"Prednisone without Side Effects": The JAK Inhibitor Ceiling in Dermatology
Discussing Changes to Atopic Dermatitis Guidelines, with Robert Sidbury, MD, MPH
Ghada Bourjeily, MD: Research Gaps on Sleep Issues During Pregnancy
John Winkelman, MD, PhD: When to Use Low-Dose Opioids for Restless Legs Syndrome
Bhanu Prakash Kolla, MBBS, MD: Treating Sleep with Psychiatric Illness
How Will Upadacitinib, Povorcitinib Benefit Hidradenitis Suppurativa?
© 2024 MJH Life Sciences

All rights reserved.