Rituximab for Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH)

Summary

Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a serious, life-threatening manifestation of systemic sclerosis (SSc), an autoimmune disease of the connective tissue characterized by scarring (fibrosis) and atrophy of the skin, joints and tendons, skeletal muscles, and internal organs, and immunological disturbances. One-year survival for patients with SSc-PAH ranges from 50-81%. There is currently no cure for SSc-PAH and treatment is limited to vasodilator therapy used in all forms of PAH. In recent studies, immunotherapy was shown to be effective in treating SSc-interstitial lung disease, another serious, life-threatening manifestation of SSc. In addition, there are compelling pre-clinical data and anecdotal clinical reports that suggest modulation of the immune system may be an effective strategy for treating SSc-PAH. To test this approach, this trial will determine if rituximab, an immunotherapy, has a marked beneficial effect on clinical disease progression, with minimal toxicity, in patients with SSc-PAH when compared to placebo.

Timeline

Start

2011-06-24

Primary completion

2018-06-05

Completion

2019-12-15

Publications

• Results Zamanian RT, Badesch D, Chung L, Domsic RT, Medsger T, Pinckney A, Keyes-Elstein L, D'Aveta C, Spychala M, White RJ, Hassoun PM, Torres F, Sweatt AJ, Molitor JA, Khanna D, Maecker H, Welch B, Goldmuntz E, Nicolls MR. Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis-associated Pulmonary Arterial Hypertension: A Multicenter, Double-Blind, Randomized, Placebo-controlled Trial. Am J Respir Crit Care Med. 2021 Jul 15;204(2):209-221. doi: 10.1164/rccm.202009-3481OC.
• Results Zhang Y, Michelakis ED. A Phase-2 NIH-sponsored Randomized Clinical Trial of Rituximab in Scleroderma-associated Pulmonary Arterial Hypertension Did Not Reach Significance for Its Endpoints: End of Story? Not So Fast! Am J Respir Crit Care Med. 2021 Jul 15;204(2):123-125. doi: 10.1164/rccm.202103-0612ED. No abstract available.
• Results Andreasson K, Bengtsson MF, Bostrom C, Hesselstrand R, Volkmann ER. Multiple Manifestations of Systemic Sclerosis Affect Walk Distance. Am J Respir Crit Care Med. 2021 Aug 1;204(3):359. doi: 10.1164/rccm.202104-0938LE. No abstract available.
• Results Zamanian RT, Pinckney A, Domsic RT, Medsger T, Keyes-Elstein L, Sweatt AJ, Welch B, Goldmuntz E, Nicolls MR, Chung L. Reply to Andreasson et al.: Multiple Manifestations of Systemic Sclerosis Affect Walk Distance. Am J Respir Crit Care Med. 2021 Aug 1;204(3):377-378. doi: 10.1164/rccm.202104-1023LE. No abstract available.
• de Bourcy CFA, Dekker CL, Davis MM, Nicolls MR, Quake SR. Dynamics of the human antibody repertoire after B cell depletion in systemic sclerosis. Sci Immunol. 2017 Sep 29;2(15):eaan8289. doi: 10.1126/sciimmunol.aan8289.

Drugs

Indications