New second-line drugs boost platelets in adults with ITP: Data
Therapies target immune pathways involved in autoimmune attacks
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New classes of second-line drugs targeting the immune pathways involved in the autoimmune attacks that cause immune thrombocytopenia (ITP) significantly boost platelet counts in adults, according to a pooled analysis of data from several clinical trials.
Notably, SYK inhibitors, including Tavalisse (fostamatinib), appeared to be the most effective, increasing the likelihood of a clinically meaningful platelet response by more than 10-fold over a placebo, the data showed.
“These findings can help clinicians make informed decisions when selecting second-line or subsequent therapies for adult patients with ITP,” researchers wrote.
The results were described in the study “Efficacy and safety of IgG-pathway inhibitors in adult immune thrombocytopenia: A systematic review and meta-analysis with subgroup analyses of FcRn and SYK inhibitors,” which was published in the journal Cytokine.
Second-line drugs interfere with key pathway
ITP occurs when the immune system mistakenly produces self-targeting antibodies that attack and destroy the body’s platelets, the cell fragments responsible for blood clotting. Low levels of platelets, medically known as thrombocytopenia, lead to symptoms such as easy bruising and bleeding.
Traditional first-line ITP treatments include anti-inflammatory corticosteroids and intravenous immunoglobulin, which delivers healthy antibodies to the patient and is thought to help prevent platelet destruction. Still, these approaches are not effective in all patients.
Among second-line options are drugs that interfere with the immunoglobulin G (IgG) antibody pathway, which is involved in the abnormal antibody-mediated responses that drive ITP.
There are three such classes of therapies. SYK inhibitors, including Tavalisse, block a key antibody-mediated signaling step that triggers immune cells to destroy platelets. FcRn inhibitors, such as efgartigimod, accelerate the clearance of harmful antibodies from the bloodstream. The third class is BTK inhibitors, such as Wayrilz (rilzabrutinib), which suppress activity of antibody-producing cells and cells involved in platelet destruction.
SYK inhibitors showed strongest response of the 3 drug classes
In this study, an international team of researchers performed a meta-analysis of published data from clinical trials to evaluate the efficacy and safety of IgG-pathway inhibitors in adults with ITP. A database search yielded 10 adequately controlled trials comparing the study drug with a placebo.
“By synthesizing current evidence related to their clinical efficacy, safety profiles, and therapeutic outcomes, this study seeks to inform evidence-based decision-making and foster the advancement of personalized medicine approaches in ITP management,” the team wrote.
SYK inhibitors showed the strongest response of the three drug classes. Patients on SYK inhibitors were significantly more likely, by 10 times, to achieve a composite durable, sustained, or stable platelet response than those on the placebo.
This response was defined as a platelet count of at least 50 billion cells/L — the level associated with a meaningfully reduced bleeding risk — in most scheduled visits between about three and six months of treatment without the need for rescue medications.
Overall response rate, defined as achieving a platelet count of at least 50 billion cells/L at least once without rescue therapy, was also significantly higher, by more than 4.5 times, with SYK inhibitors than with the placebo. Patients on these therapies were also significantly less likely, by 41%, to need rescue therapy.
SYK inhibitors were associated with a 16% higher risk of any adverse events than placebo. Still, there was no significant increase in serious adverse events or in participants stopping treatment because of adverse events.
IgG-pathway inhibitors could offer effective and safe treatment options for adult patients with ITP, with SYK inhibitors showing the most consistent efficacy and safety profiles based on current evidence.
FcRn inhibitors also showed meaningful benefits in composite platelet response, with treated patients being three times as likely to respond as those given the placebo. However, FcRn inhibitors did not significantly reduce the need for rescue therapy.
This therapy class “may exhibit a delayed therapeutic effect, which could underestimate their benefit in early response assessments,” the researchers wrote.
FcRn inhibitors showed no significant difference from placebo in any adverse events, serious adverse events, or treatment discontinuation.
The meta-analysis included only one trial testing BTK inhibitors, specifically Wayrilz. In that study, a composite platelet response was achieved in 23% of the Wayrilz group compared with 0% in the placebo group. Rescue therapy use was reduced by 52% with Wayrilz. However, because this evidence comes from a single trial, the researchers describe the overall evidence for BTK inhibitors as inconclusive.
When the researchers combined all three drug classes in an exploratory pooled analysis, IgG-pathway inhibitors as a group were associated with a nearly six-fold higher likelihood of achieving a composite platelet response than the placebo. A threefold higher overall response rate and a 39% reduction in rescue therapy use were also associated with the use of these drugs.
“IgG-pathway inhibitors could offer effective and safe treatment options for adult patients with ITP, with SYK inhibitors showing the most consistent efficacy and safety profiles based on current evidence,” the team concluded. “However, current evidence remains insufficient to confirm these findings for FcRn [inhibitors] and especially BTK inhibitors in adults with ITP.”
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