PNH Clinical Case Review

Ilene C. Wetiz, MD, professor of clinical medicine at the Keck School of Medicine at the University of Southern California, discusses the selected treatment and the results of the case:

"For the C5 inhibitors, eculizumab is given every 2 weeks. Eculizumab is short-acting and it’s been demonstrated to show a reduction in hemolysis as measured by the LDH, improvement in the overall fatigue, quality of life. There may be an improvement in the platelet count as well. And there’s clearly a reduction in thromboembolic events, with the P-value that goes out over six zeros. There’s improvement in survival and it’s safe to give in pregnancy.

Ravulizamab, which is built on the backbone of eculizumab, is noninferior to eculizumab and there are fewer breakthrough events due to inadequate dosing. Pegcetacoplan [APL-2, Apellis Pharmaceuticals], which is a cyclic C3 inhibitor, improved hemoglobins from baseline as compared to eculizumab and did improve fatigue. There were no observed thromboembolic events in those clinical trials. But most of the patients were already on a C5 inhibitor before they were exposed to pegcetacoplan.

So, what happened to this patient? She was started on low-molecular-weight heparin with improvement in her D-dimers. And then ultimately transitioned to rivaroxaban [Xarelto, Janssen], which was oral. Thrombolysis was not done because of the concerns about a hematoma in the pelvis. The patient was started on anticompliment therapy initially with eculizumab and then transitioned to ravulizamab when it became available. She had a significant breakthrough event with a COVID infection and needed some supplemental dosing even with the ravulizamab. She’s still on treatment with the long-acting C5 inhibitor and actually doing very well. Her LDH is below the upper limit of normal. And the Budd-Chiari has reversed."