Lower Risk of Cardiovascular, Metabolic Outcomes Associated With Rituximab for Pemphigus Treatment


Patients with pemphigus reported lower risk of myocardial infarction and stroke, among other cardiovascular and metabolic outcomes, when treated with rituximab compared with the first-line corticosteroid-sparing agents azathioprine and mycophenolate mofetil.

Rituximab may be a preferred treatment option vs first-line corticosteroid-sparing agents for patients with pemphigus who are at risk for cardiovascular and metabolic conditions, according to study findings published in JAMA Dermatology.

Pemphigus is a potentially life-threatening autoimmune skin disease, and patients with the condition are more susceptible to death compared with the general population. Proper treatment, particularly with the first-line corticosteroid-sparing agents mycophenolate mofetil (MMF) and azathioprine, has been shown to substantially reduce risk of mortality.

“However, the main challenge in treating pemphigus is to maintain long-term remission with the smallest dose of systemic corticosteroids for the shortest time, aiming to mitigate their life-threatening adverse events,” said the study authors.

Another alternative treatment option, rituximab, a monoclonal chimeric mouse/human antibody directed against CD20-expressing B lymphocytes, has also shown promising efficacy for the condition. Recent research showed that rituximab was superior to MMF in producing sustained complete remission and achieving a lower cumulative dose of corticosteroids, but more patients receiving treatment with rituximab experienced severe adverse events.

“While this study illuminated the safety profile of these drugs, our knowledge about the long-term complications of rituximab, MMF, and azathioprine remains sparse,” said researchers.

They conducted a global population–based retrospective cohort study to further assess the risk of long-term cardiovascular and metabolic outcomes and all-cause mortality in patients with pemphigus managed by rituximab (n = 961; mean [SD] age, 54.8 [16.6] years) compared with those receiving treatment with azathioprine and MMF (n = 961; mean (SD) age, 54.4 [18.2] years).

Eligible patients were enrolled from the Global Collaborative Network of TriNetX platform and underwent propensity score matching to optimize comparability. The primary outcomes examined were risk of myocardial infarction, stroke, peripheral vascular disease, pulmonary embolism, hypertension, hyperlipidemia, type 2 diabetes, obesity, osteoporosis, and avascular bone necrosis.

A total of 1602 participants were included in the analysis, of whom 855 (53.4%) were women and 747 (46.6%) were men.

Compared with those treated with azathioprine/MMF, patients treated with rituximab experienced a lower risk of several cardiovascular and metabolic outcomes:

  • Myocardial infarction (relative risk [RR], 0.45; 95% CI, 0.24-0.86; P = .01)
  • Stroke (RR, 0.42; 95% CI, 0.26-0.69; P < .001)
  • Peripheral vascular disease (RR, 0.47; 95% CI, 0.28-0.79; P = .003)
  • Hypertension (RR, 0.48; 95% CI, 0.38-0.63; P < .001)
  • Hyperlipidemia (RR, 0.45; 95% CI, 0.32-0.64; P < .001)
  • Type 2 diabetes (RR, 0.63; 95% CI, 0.51-0.77; P < .001)
  • Obesity (RR, 0.49; 95% CI, 0.34-0.72; P < .001)
  • Osteoporosis (RR, 0.46; 95% CI, 0.30-0.71; P < .001)

Risk of pulmonary embolism and avascular necrosis of the bone was shown to be similar between both groups. Moreover, all-cause mortality was comparable between patients in both groups (HR, 0.94; 95% CI, 0.62-1.43; log-rank P = .77). Thirty-seven deaths occurred in the rituximab group compared with 60 in the azathioprine/MMF group.

The use of retrospective data was cited as a potential limitation of the analysis, as well as the lack of clinical data about the immunological and clinical features of the disease, which interfered with investigating the efficacy of treatment.

“Clinicians treating patients with pemphigus should be aware of the study findings,” concluded the study authors. “Rituximab might be considered positively in individuals with cardiovascular and metabolic risk factors, for whom corticosteroid-related adverse events must be avoided.”


Kridin K, Mruwat N, Ludwig RJ. Association of rituximab with risk of long-term cardiovascular and metabolic outcomes in patients with pemphigus. JAMA Dermatol. Published online November 30, 2022. doi:10.1001/jamadermatol.2022.5182

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