B-Cell Depletion Therapy May Be Safe, Effective for Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH). CT scan of the thorax
Researchers assessed the safety and efficacy of B-cell depletion for systemic sclerosis-associated pulmonary arterial hypertension.

Depletion of B cells with rituximab may be safe and effective in the adjuvant treatment of systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH), according to study results published in the American Journal of Respiratory and Critical Care Medicine.

Among patients with SSc, pulmonary hypertension may result from several etiologies, including interstitial lung disease, pulmonary veno-occlusive disease, chronic thromboembolic disease, and/or pulmonary arterial hypertension. Because B cells play a key role in the pathogenesis of SSc, B-cell depletion may serve as an important treatment option for SSc-PAH.

The objective of the current study was to explore the safety and efficacy of B-cell depletion with rituximab in patients with SSc-PAH.

The proof-of-concept, double-blind, multicenter, phase 2 randomized clinical trial included adults aged between 18 and 75 years with SSc-PAH who were diagnosed for 5 years or less. Study participants were randomly assigned 1:1 to receive either 2 infusions of 1000 mg of rituximab or placebo, administered 2 weeks apart. All participants were followed up for 48 weeks.

The primary outcome was the change from time of enrollment to week 24 in the 6-minute walk distance. Secondary endpoints were safety and invasive hemodynamics.

The study sample included 57 patients with SSc-PAH on stable-dose standard medical therapy.

The adjusted mean change in 6-minute walk distance from baseline to week 24 was better with rituximab than placebo, but the difference was not statistically significant (23. 6 vs 0.5 meters, P =.12). However, the estimated treatment group difference at week 24, based on the secondary analysis model that included 6-minute walk distance data to week 48 was statistically significant (25.1 vs 0.4 meters, P =.03).

Treatment with rituximab was safe and well tolerated, and the differences in adverse event rates between the groups were not unexpected. Infections were the most common severe adverse events in patients who received rituximab (10 events in 7 patients; 24.1%) and were more common compared with the placebo group (3 events in 2 patients; 7.1%), but none were fatal. At 1 year, mortality rates were 14% in rituximab and 4% in placebo groups; however, none of these deaths were attributed to rituximab use.

Several predictors of improved 6-minute walk distance in response to rituximab were identified, including low levels of rheumatoid factor, interleukin (IL)-12 and IL-17.

The study had several limitations, including low enrollment rate, relatively small sample size, and inability to identify smaller differences in the primary outcome. In addition, the original primary outcome was changed during the study.

“This study suggests a possible role for adjunctive immunotherapy for targeted patients with systemic sclerosis-associated PAH,” the researchers concluded.


Zamanian RT, Badesch D, Chung L, et al. Safety and efficacy of B-cell depletion with rituximab for the treatment of systemic sclerosis associated pulmonary arterial hypertension: a multi-center, double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. Published online March 2, 2021. doi:10.1164/rccm.202009-3481OC