Therapy combo helps 92% of patients with hard-to-treat ITP in trial
Eltrombopag with cyclosporine A eases bleeding, but caution urged
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A combination of the medicines eltrombopag and cyclosporine A may be effective for controlling immune thrombocytopenia (ITP) that doesn’t respond well to initial treatment with corticosteroids, though caution is needed due to a risk of life-threatening adverse events for some patients, according to a new study.
The researchers noted that the therapy combo showed benefits for more than 90% of adults participating in the clinical study testing it. Still, the use of the treatment combination led to serious side effects for nearly 15% (a total of 4) of the participants, with two dying as a result of subsequent infections.
“This prospective Phase [2] study demonstrates that the combination of [eltrombopag and cyclosporine A] is a highly effective and rapidly acting therapeutic strategy for adult patients with corticosteroid-[resistant] ITP,” the researchers wrote, adding that the treatment combination’s risk-benefit profile “appears favorable for most patients.”
However, “vigilant toxicity management … is essential and [the regimen’s use] requires careful monitoring and patient education,” the team wrote.
The study, “Efficacy and safety of eltrombopag in combination with cyclosporine A for the treatment of adult refractory primary immune thrombocytopenia: a phase II, multicenter, single-arm, prospective study,” was published in the journal Clinical and Experimental Medicine.Â
ITP is a disorder in which the immune system attacks and destroys platelets, which are cell fragments that normally help blood clot. Low platelet levels in ITP lead to issues such as abnormally easy and prolonged bleeding.
First-line treatment for ITP usually involves corticosteroids, which are medicines that suppress the immune system by mimicking the activity of the stress hormone cortisol. But corticosteroids don’t work for everyone. In others, the disease does respond, but it flares up again as soon as corticosteroids are stopped.
Additionally, long-term corticosteroid treatment can lead to a wide range of side effects that include mood changes, weight gain, and skin problems.
2 therapies used in combination shown to ease symptoms
Here, scientists in China conducted a clinical trial to test the combination of eltrombopag and cyclosporine A in 28 patients whose ITP was treatment-resistant. Cyclosporine A is an immunosuppressant, a medication that suppresses the immune system. Eltrombopag, the active agent in Alvaiz and Promacta, works by stimulating the body to produce new platelets. The initial dose used in the study was 50 mg eltrombopag nightly and cyclosporine Aat 3 mg/kg/day; doses were adjusted based on each patient’s response to treatment.
A total of 25 participants completed the eight-week treatment course. Almost all of them — 23 or 92% — responded to the treatment, with platelet levels rising to at least 30 billion per liter of blood. More than 70% of the patients had a complete response, with platelet counts of at least 100 billion per liter of blood.
The median time from starting treatment to meeting response criteria was about two weeks, and the increase in platelet levels was accompanied by a decrease in bleeding symptoms. After six months of follow-up, most patients who responded (18 of 23) still had platelet counts of about 30 billion per liter.
The researchers noted that these response rates “compare very favorably” with historical data for either eltrombopag or cyclosporine A used on their own in ITP patients. This “likely stems from their complementary mechanisms of action,” the researchers said: Eltrombopag boosts platelet production while cyclosporine A prevent platelet destruction.
[This regimen] represents a viable and highly effective salvage therapy [for people with treatment-resistant ITP].
Safety data showed that the combination of eltrombopag and cyclosporine A was generally tolerated well; most side effects were mild or moderate. However, four patients experienced serious side effects. Two of the patients who had serious side effects ended up discontinuing treatment, but the other two died as a result of serious infections. These individuals were both older and had underlying health conditions, but the researchers said the fact that they were taking an immune-suppressing therapy also likely played a role.
“This underscores a fundamental aspect of the regimen’s risk-benefit profile: The potent [immune suppression] required [to effectively treat ITP] simultaneously increases vulnerability to opportunistic and severe infections,” the researchers wrote.
ITP treatment comes with a high risk of complications
In short, according to the team, people with ITP are at a high risk for complications when receiving treatment.
“Consequently, this finding necessitates not only rigorous patient selection — with especially cautious evaluation of elderly and medically complex individuals — but also mandates proactive strategies” to reduce the risk of severe infections, the researchers said.
Overall, although appropriate caution is needed to manage risks, the researchers concluded that the combination of eltrombopag and cyclosporine A “represents a viable and highly effective salvage therapy” for people with ITP that doesn’t respond well to first-line corticosteroid treatment.
