PMID- 36439640
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221129
IS  - 1759-720X (Print)
IS  - 1759-7218 (Electronic)
IS  - 1759-720X (Linking)
VI  - 14
DP  - 2022
TI  - Higher body mass index is associated with a lower iloprost infusion rate 
      tolerance and higher iloprost-related adverse events in patients with systemic 
      sclerosis.
PG  - 1759720X221137125
LID - 10.1177/1759720X221137125 [doi]
LID - 1759720X221137125
AB  - BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by 
      vasospasm and microvascular involvement. Iloprost (ILO), a prostaglandin 
      analogous, is used for the treatment of SSc-related Raynaud's phenomenon and 
      digital ulcers. The suggested dose is 0.5-2 ng/kg/min for 6-8 h, and the maximum 
      dose is decided upon the patient's tolerance. OBJECTIVES: This study aims to 
      analyze ILO infusion tolerance and possible predictive factors in patients with 
      SSc. DESIGN: This is a retrospective observational study. METHOD: We evaluated 
      113 patients with SSc beginning ILO intravenous (IV) infusion treatment between 
      2004 and 2021. We assessed the maximum tolerated ILO IV infusion rate, the 
      incidence of adverse events (AEs), and the need for symptomatic therapy during 
      the dose-finding sessions. We collected relevant demographic and medical and 
      employed generalized linear models to assess possible predictors of maximum 
      tolerated ILO infusion rate and AEs and logistic regression to assess predictors 
      of AEs. RESULTS: The median ILO infusion rate at the end of the dose-finding 
      process was 0.88 ng/kg/min [interquartile range (IQR) = 0.37]. We found a 
      significant inverse correlation between ILO infusion rate and body mass index 
      (BMI) at the beginning of treatment. BMI was negatively associated with ILO 
      infusion rate (beta = -0.21, p = 0.02) after correction for relevant confounding 
      factors. Overweight patients (BMI >26) presented a 13-fold increased risk of 
      developing AEs during ILO titration [adjusted odds ratio = 13.979, 95% confidence 
      interval (CI) = 2.359-82.845]. AEs during ILO titration occurred in 47.8% of 
      patients, of whom 22.2% presented hypotension. Other AEs were headache, nausea, 
      vomiting, diarrhea, and edema. Symptomatic therapy was needed in half of the 
      patients at least once. CONCLUSION: This study showed that higher BMI was 
      statistically associated with lower ILO infusion rate tolerance and higher AEs 
      rate, underlying a possible BMI-dependent endothelial dysfunction. Individual ILO 
      regimens still need to be tailored to the patient. PLAIN LANGUAGE SUMMARY: 
      Introduction: Systemic sclerosis is a rare a rheumatic disease characterized by 
      skin thickening, vasospasm, and digital ulcers (DUs), as well as other organs 
      involvement. Iloprost, which is administered as intravenous infusion, is one of 
      the main treatments for this disease, and it is effective in reducing vasospasm 
      and the frequency of DUs. Even if there is a suggested dose range, the exact dose 
      must be tailored on each patient, because the tolerance to the drug is variable. 
      Tolerance is limited by dose-dependent unwanted effects, as headache, low blood 
      pressure, dizziness, and sickness. This study aimed to identify possible 
      predictors of such tolerance.Materials and Methods: We collected data from our 
      patients with systemic sclerosis beginning the treatment with iloprost between 
      January 2004 and November 2021 at our hospital facility in Verona, Italy, and 
      analyzed different factors that could be associated with a better tolerance, as 
      age, sex, disease duration, smoking habit, body mass index (a measure of body 
      fatness), blood pressure, concomitant medications, and different patterns of the 
      disease.Results: We found that a higher body mass index was associated with lower 
      iloprost tolerance and higher adverse events rate in patients with systemic 
      sclerosis, while we did not find a correlation with other factors. We believe 
      overweight and obese patients (who have a higher body mass index) have a defect 
      in the vasodilatation mechanism and can therefore be more susceptible to the 
      effect of this medication.Conclusions: While preliminary, our results could 
      provide a good starting point to develop a predictive tool to limit adverse 
      events during this therapy.
CI  - (c) The Author(s), 2022.
FAU - Bixio, Riccardo
AU  - Bixio R
AUID- ORCID: 0000-0001-9335-3371
AD  - Rheumatology Section, Department of Medicine, University of Verona, Policlinico 
      G.B. Rossi 10, 37134 Verona, Italy.
FAU - Adami, Giovanni
AU  - Adami G
AUID- ORCID: 0000-0002-8915-0755
AD  - Rheumatology Section, Department of Medicine, University of Verona, Verona, 
      Italy.
FAU - Bertoldo, Eugenia
AU  - Bertoldo E
AD  - Rheumatology Section, Department of Medicine, University of Verona, Verona, 
      Italy.
FAU - Giollo, Alessandro
AU  - Giollo A
AUID- ORCID: 0000-0001-9355-7673
AD  - Division of Rheumatology, University of Padova, Padova, Italy.
FAU - Morciano, Andrea
AU  - Morciano A
AD  - Rheumatology Section, Department of Medicine, University of Verona, Verona, 
      Italy.
FAU - Bertelle, Davide
AU  - Bertelle D
AUID- ORCID: 0000-0002-5901-7742
AD  - Rheumatology Section, Department of Medicine, University of Verona, Verona, 
      Italy.
FAU - Orsolini, Giovanni
AU  - Orsolini G
AD  - Rheumatology Section, Department of Medicine, University of Verona, Verona, 
      Italy.
FAU - Idolazzi, Luca
AU  - Idolazzi L
AUID- ORCID: 0000-0002-7254-4686
AD  - Rheumatology Section, Department of Medicine, University of Verona, Verona, 
      Italy.
FAU - Rossini, Maurizio
AU  - Rossini M
AUID- ORCID: 0000-0001-9692-2293
AD  - Rheumatology Section, Department of Medicine, University of Verona, Verona, 
      Italy.
FAU - Viapiana, Ombretta
AU  - Viapiana O
AD  - Rheumatology Section, Department of Medicine, University of Verona, Verona, 
      Italy.
LA  - eng
PT  - Journal Article
DEP - 20221122
PL  - England
TA  - Ther Adv Musculoskelet Dis
JT  - Therapeutic advances in musculoskeletal disease
JID - 101517322
PMC - PMC9685102
OTO - NOTNLM
OT  - body mass index
OT  - iloprost
OT  - prostanoids
OT  - systemic sclerosis
COIS- The authors declared no potential conflicts of interest with respect to the 
      research, authorship, and/or publication of this article. The Associate Editor of 
      Therapeutic Advances in Musculoskeletal Disease (Giovanni A is an author of this 
      paper, therefore, the peer review process was managed by alternative members of 
      the Board and the submitting Editor was not involved in the decision-making 
      process.
EDAT- 2022/11/29 06:00
MHDA- 2022/11/29 06:01
PMCR- 2022/11/22
CRDT- 2022/11/28 04:41
PHST- 2022/05/09 00:00 [received]
PHST- 2022/10/12 00:00 [accepted]
PHST- 2022/11/28 04:41 [entrez]
PHST- 2022/11/29 06:00 [pubmed]
PHST- 2022/11/29 06:01 [medline]
PHST- 2022/11/22 00:00 [pmc-release]
AID - 10.1177_1759720X221137125 [pii]
AID - 10.1177/1759720X221137125 [doi]
PST - epublish
SO  - Ther Adv Musculoskelet Dis. 2022 Nov 22;14:1759720X221137125. doi: 
      10.1177/1759720X221137125. eCollection 2022.