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25 mcg JJA Venom Immunotherapy Matches 50 mcg Efficacy, With Adriana Le Thanh-Thao, MBBS
Q&A with Le Thanh-Thao on trial data showing 25 mcg of JJA VIT matched 50 mcg efficacy, with safety and biomarker insights.
Low-dose (25 mcg) jack jumper ant (JJA) venom immunotherapy (VIT) demonstrated similar protection to standard 50 mcg dosing, with 85% of participants tolerating a sting challenge after 12 months.
These findings come from a phase 1/2 single-blind randomized controlled trial of 49 adults aged 18 – 65 years with prior systemic allergic reactions to JJA stings, with 44 initiating treatment (either 25 mcg venom + delta-inulin (n = 10), 25 mcg venom with no delta-inulin (n = 11), 50 mcg venom + delta-inulin (n = 12), or 50 mcg venom with no delta-inulin (n = 11)) and 40 undergoing a sting challenge. Investigators observed no difference between dosing groups (odds ratio [OR], 0.89; 95% CI, 0.38–2.09; P =.98) or with the addition of delta-inulin (Advax) (OR, 0.99; 95% CI, 0.42–2.33). Greater dosing reduced systemic reactions (OR, 0.53; 95% CI, 0.28–0.98).
HCPLive spoke with investigator Adriana Le Thanh-Thao, MBBS, FRACP, from the Royal Hobart Hospital Jack Jumper Allergy Program to contextualize these findings for clinical practice. In this Q&A, Le Thanh-Thao discussed dose selection, safety trade-offs, the role of delta-inulin, and how clinicians should interpret emerging biomarker data in venom immunotherapy.
HCPLive: What do the findings suggest about the comparative efficacy of 25 mcg versus 50 mcg maintenance dosing for jack jumper ant venom immunotherapy?
Le Thanh-Thao: 85% of participants who completed the trial protocol passed [the] deliberate sting challenge after 12 months of maintenance [with] JJA VIT. The sting challenge outcomes were similar between the 25mcg and 50mcg VIT groups, suggesting low-dose JJA VIT may be non-inferior to the current standard dose.
HCPLive: Given similar efficacy, what are the potential advantages and trade-offs of using a lower 25 mcg maintenance dose in clinical practice?
Le Thanh-Thao: JJA venom for VIT is costly and resource-intensive to produce. A lower maintenance dose would be associated with significant healthcare savings for the institutions providing JJA VIT and potentially increase the capacity to treat more patients.
Shortages of JJA venom are a risk, as there is only one manufacturer of the product, and a lower maintenance dose would mitigate the impact of a shortage should it occur.
It is unknown if the 25 mcg dose is protective against multiple stings or will be less likely than higher VIT doses to induce mechanisms of long-term immune tolerance, which are desired to provide ongoing protection from stings after completing a 3–5-year course of VIT.
While we expected a lower VIT dose to be associated with [fewer] allergic side effects (as has previously been found when comparing 50 mcg vs. 100 mcg JJA VIT), in our current study, systemic allergic reactions were more common with the lower VIT dose. Further studies would be required to determine if this is a true effect, in which case it may reflect the observation that some patients require a higher VIT dose compared to others to induce tolerance.
HCPLive: How did the addition of delta-inulin influence clinical outcomes, and should it be considered in routine venom immunotherapy protocols?
Le Thanh-Thao: Advax enhanced sIgG4 responses when combined with the standard JJA VIT dose, but this did not correlate with an improvement in clinical outcome in terms of either efficacy or treatment-related side effects. As a result, it should not yet be considered in routine VIT protocols. Advax may still have immunomodulatory benefits with longer-term VIT treatment, including after cessation of treatment, but this would require further studies.
HCPLive: How should clinicians weigh the finding that greater maintenance dosing was associated with fewer treatment-related systemic reactions?
Le Thanh-Thao: The number of participants in this study was relatively small, so it is possible this is a chance result, and a larger study would be required to confirm this finding. However, it is well recognized that some bee and wasp venom-allergic patients do not have clinical protection with standard 100 mcg maintenance dosing, which is evidenced by systemic reactions to VIT or stings while in the maintenance phase of therapy. Increasing to a higher VIT maintenance dose (e.g., 200 mcg) in these patients has been shown to confer protection. It may be a similar scenario with the low-dose JJA VIT patients having systemic reactions to VIT, requiring a higher dose to induce tolerance.
HCPLive: What do the safety data indicate about the risk of systemic reactions during the build-up versus maintenance phases of therapy?
Le Thanh-Thao: Systemic reactions are most common during the build-up phase and uncommon during the maintenance phase of therapy. While systemic reactions to JJA VIT are common, occurring in around one-third of patients when using a semi-rush build-up protocol, the majority of these reactions are mild and non-recurrent.
HCPLive: How might basophil activation test trends inform clinical decision-making or risk stratification in venom immunotherapy?
Le Thanh-Thao: This study found a decrease in basophil activation from baseline was associated with having a negative sting challenge after 12 months of VIT. A decline in BAT sensitivity, therefore, has the potential [to be] a biomarker for predicting the development of clinical tolerance to stings. However, these findings would need to be replicated in larger studies to confirm BAT’s robustness as a biomarker of successful VIT.
HCPLive: In the absence of clear biomarker predictors, how should clinicians currently assess treatment success and protection against future stings?
Le Thanh-Thao: At present, there is still no established biomarker for gauging VIT success, which is instead assessed clinically by reactivity to stings (either accidental field stings or with deliberate sting challenge) during and after a course of VIT. However, while stings are the ‘gold standard’ test, they have some limitations in regard to their negative predictive value. Tolerance to a single sting during or following a course of VIT is still not a guarantee of tolerance to subsequent stings, as the natural history of reactivity to stings is variable in allergic patients, who may tolerate their next sting [and] then react to a subsequent sting.
HCPLive: Based on these findings, is there sufficient evidence to support adopting lower-dose venom immunotherapy?
Le Thanh-Thao: This was a pilot phase 1/2 study, and the number of participants was relatively small. Larger studies would be required to confirm the non-inferiority of lower VIT dosing.
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