Most immune reactions after PNH treatment switch are manageable
Quick corticosteroid treatment proves successful, analysis shows
People switching between treatments for paroxysmal nocturnal hemoglobinuria (PNH) may develop transient immune complex reactions (TICRs) — a type of inflammatory reaction — but these are usually not serious and manageable, a new analysis of more than 200 people finds.
The analysis covered people who switched from Soliris (eculizumab) or Ultomiris (ravulizumab-cwvz) to PiaSky (crovalimab-akkz).
The study, “Managing transient immune complex reactions in patients with paroxysmal nocturnal hemoglobinuria: clinical observations from the COMMODORE 1 and 2 studies,” was published in Therapeutic Advances in Hematology. The work was funded by Roche, which markets PiaSky.
In PNH, part of the immune system (called the complement cascade) becomes abnormally activated to destroy the body’s own healthy blood cells. Soliris, Ultomiris, and PiaSky are all approved PNH treatments that work to block complement activation by targeting a protein called C5.
Soliris and Ultomiris both target the same region of the C5 protein, but PiaSky targets a different part of the protein. When people switch from Soliris or Ultomiris to PiaSky, it is possible for complexes where the C5 protein is bound to the two drugs at once to form. This can lead to inflammatory reactions known as TICRs.
Analysis of the COMMODORE studies
Researchers analyzed the frequency and severity of TICRs among 201 patients who switched from Soliris or Ultomiris to PiaSky, using data from two Phase 3 clinical trials — COMMODORE 1 (NCT04432584) and COMMODORE 2 (NCT04434092).
Results showed TICRs were reported in just less than one-fifth (19%) of the people. Mild or moderate reactions occurred in 11% of patients, while 8% had severe TICRs. None were life-threatening or fatal.
Researchers conducted statistical analyses to look for factors that might increase a person’s predisposition to TICRs, but they did not identify any statistically significant risk factors.
Among people who had a TICR, the median time from starting PiaSky to the onset of the reaction was about 11 days (1.6 weeks). The most common TICR symptoms included joint pain, rash, and fever. Some people, particularly those with more severe TICRs, also saw other symptoms like headache and muscle pain.
Most patients who had a TICR received treatments to manage the reaction. Corticosteroids — powerful anti-inflammatory therapies — were the most common treatment used. Other medications, ranging from antihistamines to opioids, also helped manage TICR for some people.
As of the latest follow-up, almost all TICR events had been resolved. Most reactions were quite short and resolved within days of appearing. The researchers noted more severe TICRs generally required higher corticosteroid doses but resolved in a similar amount of time as milder reactions.
The results show “TICRs that occurred from switching between C5 inhibitors were generally mild to moderate and resolved with appropriate treatment,” the researchers wrote, adding that these findings “serve to provide practical clinical guidance for the management of TICRs when switching between C5 inhibitors.”
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