Epicutaneous immunotherapy for treatment of peanut allergy: Follow-up from the Consortium for Food Allergy Research.

BACKGROUND: Consortium for Food Allergy Research investigators previously reported 52-week outcomes from a randomized controlled trial of peanut epicutaneous immunotherapy, observing modest and statistically significant induction of desensitization, highest in children ages 4 to 11 years. OBJECTIVE: We sought to evaluate changes in efficacy, safety, and mechanistic parameters following extended open-label peanut epicutaneous immunotherapy. METHODS: Peanut-allergic participants (4-25 years) received 52 weeks of placebo (PLB), Viaskin Peanut 100 µg (VP100) or 250 µg (VP250), and then crossed over to VP250 for PLB (PLB-VP250) and VP100 (VP100-VP250) participants and continued treatment for VP250 participants (total = 130 weeks of active epicutaneous immunotherapy). Efficacy was assessed by double-blind, placebo-controlled food challenge (5044 mg peanut protein), and adherence, safety, and mechanistic parameters were evaluated. RESULTS: At week 130, desensitization success was achieved in 1 of 20 (5%) PLB-VP250, 5 of 24 (20.8%) VP100-VP250, and 9 of 25 (36%) VP250 participants, with median successfully consumed dose change from baseline of 11.5 mg, 141.5 mg, and 400 mg, respectively. Median age (years) for week 130 desensitization success was 6.2 years (interquartile range, 5.2-9.1) versus 9.4 years (interquartile range, 7.6-12.8) for failures (P < .001). Adherence was 96%. Adverse reactions were predominantly local patch-site reactions. Significant increases in peanut- and Ara h2-specific IgG4 observed at week 52 persisted to week 130. By a post hoc analysis, there were no statistically significant increases from week 52 to week 130 in either desensitization success or successfully consumed dose. CONCLUSIONS: Extended treatment with VP250 was well tolerated, and desensitization observed at week 52 persisted between weeks 52 and 130. Treatment success was observed predominantly in younger participants, with younger age at initiation of active therapy an important predictor of success.

Early epitope-specific IgE antibodies are predictive of childhood peanut allergy.

BACKGROUND: Peanut allergy is characterized by the development of IgE against peanut antigen. OBJECTIVE: We sought to evaluate the evolution of epitope-specific (es)IgE and esIgG4 in a prospective cohort of high-risk infants to determine whether antibody profiles can predict peanut allergy after age 4 years. METHODS: The end point was allergy status at age 4+ years; samples from 293 children were collected at age 3 to 15 months and 2 to 3 and 4+ years. Levels of specific (s)IgE and sIgG4 to peanut and component proteins, and 50 esIgE and esIgG4 were quantified. Changes were analyzed with mixed-effects models. Machine learning algorithms were developed to identify a combination of antigen- and epitope-specific antibodies that using 3- to 15-month or 2- to 3-year samples can predict allergy status at age 4+ years. RESULTS: At age 4+ years, 38% of children were Tolerant or 14% had Possible, 8% Convincing, 24% Serologic, and 16% Confirmed allergy. At age 3 to 15 months, esIgE profiles were similar among groups, whereas marked increases were evident at age 2 and 4+ years only in Confirmed and Serologic groups. In contrast, peanut sIgE level was significantly lower in the Tolerant group at age 3 to 15 months, increased in Confirmed and Serologic groups but decreased in Convincing and Possibly Allergic groups over time. An algorithm combining esIgEs with peanut sIgE outperformed different clinically relevant IgE cutoffs, predicting allergy status on an "unseen" set of patients with area under the curves of 0.84 at age 3 to 15 months and 0.87 at age 2 to 3 years. CONCLUSIONS: Early epitope-specific plus peanut-specific IgE is predictive of allergy status at age 4+ years.

Induction of sustained unresponsiveness after egg oral immunotherapy compared to baked egg therapy in children with egg allergy.

BACKGROUND: While desensitization and sustained unresponsiveness (SU) have been shown with egg oral immunotherapy (OIT), the benefits of baked egg (BE) therapy for egg allergy have not been well studied. OBJECTIVES: This study sought to evaluate the safety and efficacy of BE ingestion compared with egg OIT in participants allergic to unbaked egg but tolerant to BE. METHODS: Children who are BE-tolerant but unbaked egg reactive ages 3 to 16 years were randomized to 2 years of treatment with either BE or egg OIT. Double-blind, placebo-controlled food challenges were conducted after 1 and 2 years of treatment to assess for desensitization, and after 2 years of treatment followed by 8 to 10 weeks off of treatment to assess for SU. Mechanistic studies were conducted to assess for immune modulation. A cohort of participants who are BE-reactive underwent egg OIT and identical double-blind, placebo-controlled food challenges as a comparator group. RESULTS: Fifty participants (median age 7.3 years) were randomized and initiated treatment. SU was achieved in 3 of 27 participants assigned to BE (11.1%) versus 10 of 23 participants assigned to egg OIT (43.5%) (P = .009). In the BE-reactive comparator group, 7 of 39 participants (17.9%) achieved SU. More participants who are BE-tolerant withdrew from BE versus from egg OIT (29.6% vs 13%). Dosing symptom frequency in participants who are BE-tolerant was similar with BE and egg OIT, but more frequent in participants who are BE-reactive. Egg white-specific IgE, skin testing, and basophil activation decreased similarly after BE and egg OIT. CONCLUSIONS: Among children allergic to unbaked egg but tolerant to BE, those treated with egg OIT were significantly more likely to achieve SU than were children ingesting BE.

Multicenter, randomized, double-blind, placebo-controlled clinical trial of vital wheat gluten oral immunotherapy.

BACKGROUND: Wheat is a common food allergen that can cause anaphylaxis. OBJECTIVE: We sought to determine the efficacy and safety of vital wheat gluten (VWG) oral immunotherapy (OIT). METHODS: After baseline double-blind, placebo-controlled food challenge (DBPCFC), 46 patients with wheat allergy (median age, 8.7 years; range, 4.2-22.3 years) were randomized 1:1 to low-dose VWG OIT or placebo, with biweekly escalation to 1445 mg of wheat protein (WP). After a year 1 DBPCFC, active subjects continued low-dose VWG OIT for another year and underwent a year 2 DBPCFC and, if passed, a subsequent off-therapy DBPCFC. Placebo-treated subjects crossed over to high-dose VWG OIT (maximum, 2748 mg of WP). RESULTS: The median baseline successfully consumed dose (SCD) was 43 mg of WP in both groups. At year 1, 12 (52.2%) of 23 low-dose VWG OIT-treated and 0 (0%) of 23 placebo-treated subjects achieved the primary end point of an SCD of 4443 mg of WP or greater (P < .0001); median SCDs were 4443 and 143 mg, respectively. At year 2, 7 (30.4%) of 23 low-dose VWG OIT-treated subjects were desensitized to an SCD of 7443 mg of WP; 3 (13%) achieved sustained unresponsiveness 8 to 10 weeks off therapy. Among placebo-treated subjects who crossed over to high-dose VWG OIT, 12 (57.1%) of 21 were desensitized after 1 year (median SCD, 7443 mg of WP; nonsignificant vs low-dose VWG OIT). At year 1, skin prick test responses and wheat- and omega-5 gliadin-specific IgE levels did not differ between groups; the low-dose VWG OIT median specific IgG4 level was greater than placebo (wheat, P = .0005; omega-5 gliadin, P = .0001). Year 1 SCDs correlated with wheat-specific (rho = 0.55, P = .0003) and omega-5 gliadin-specific (rho = 0.51, P = .001) IgG4 levels in all subjects. Among 7822 low-dose VWG OIT doses in year 1, 15.4% were associated with adverse reactions: 0.04% were severe, and 0.08% subjects received epinephrine. Among 7921 placebo doses, 5.8% were associated with adverse reactions; none were severe. CONCLUSIONS: Low- and high-dose VWG OIT induced desensitization in about one half of the subjects after 1 year of treatment. Two years of low-dose VWG OIT resulted in 30% desensitization, and 13% had sustained unresponsiveness.

The Consortium for Food Allergy Research (CoFAR): The first generation.

The Consortium for Food Allergy Research (CoFAR) was established by the National Institute of Allergy and Infectious Diseases in 2005 as a collaborative research program bringing together centers focused on the study of food allergy. CoFAR was charged with developing studies to better understand the pathogenesis and natural history of food allergy, as well as potential approaches to the treatment of food allergy. In its first iteration an observational study of infants with milk and egg allergy was established, and studies of oral immunotherapy for egg allergy and sublingual immunotherapy for peanut allergy were initiated, as was a phase 1 study of a recombinant peanut protein vaccine. CoFAR was renewed in 2010 for an additional 5-year period during which the initial observational study was continued, a study of eosinophilic esophagitis was initiated, and new therapeutic trials were established to study epicutaneous immunotherapy for peanut allergy and to compare the safety and efficacy of egg oral immunotherapy to the ingestion of baked egg for the treatment of egg allergy. The results of these efforts will be reviewed in this rostrum, with a brief look to the future of CoFAR.

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. FINDINGS: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). INTERPRETATION: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. FUNDING: NIDA Clinical Trials Network.

Clinical factors associated with peanut allergy in a high-risk infant cohort.

BACKGROUND: Prognostication of peanut allergy (PNA) is relevant for early interventions. We aimed to determine baseline parameters associated with the development of PNA in 3- to 15-month-olds with likely egg and/or milk allergy, and/or moderate to severe atopic dermatitis (AD) and a positive egg/milk skin prick test (SPT), but no known PNA. METHODS: The primary endpoint was PNA [confirmed/convincing diagnosis or last classified as serologic PNA (<2 years, ≥5 kUA/L, otherwise ≥14 kUA/L, peanut IgE)] among 511 participants (median follow-up, 7.3 years). Associations were explored with univariate logistic regression; factors with P < 0.15 were analyzed by stepwise multiple logistic regression, using data stratified by PNA status and randomly assigned to development and validation datasets. RESULTS: 205/511 (40.1%) had PNA. Univariate factors associated with PNA (P < 0.01) included increased AD severity, larger egg and peanut SPT, greater egg, milk, peanut, Ara h1-h3 IgE, higher peanut IgG and IgG4, and increased pregnancy peanut consumption. P-values were between 0.01 and 0.05 for younger age, non-white race, lack of breastfeeding, and increased lactation peanut consumption. Using a development dataset, the multivariate model identified younger age at enrollment, greater peanut and Ara h2 IgE, and lack of breastfeeding as prognosticators. The final model predicted 79% in the development and 75% in the validation dataset (AUC = 0.83 for both). Models using stricter or less strict PNA criteria both found Ara h2 as predictive. CONCLUSIONS: Key factors associated with PNA in this high-risk population included lack of breastfeeding, age, and greater Ara h2 and peanut-specific IgE, which can be used to prognosticate outcomes.

Clinical Surveillance and Evaluation of Suspected Ebola Cases in a Vaccine Trial During an Ebola Epidemic: The Sierra Leone Trial to Introduce a Vaccine Against Ebola.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Health Conditions in an Adult Population in Sierra Leone: Data Reported From the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE).

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

The Sierra Leone Trial to Introduce a Vaccine Against Ebola: An Evaluation of rVSV∆G-ZEBOV-GP Vaccine Tolerability and Safety During the West Africa Ebola Outbreak.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Monitoring Serious Adverse Events in the Sierra Leone Trial to Introduce a Vaccine Against Ebola.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Mechanistic correlates of clinical responses to omalizumab in the setting of oral immunotherapy for milk allergy.

BACKGROUND: In our recent clinical trial, the addition of omalizumab to oral immunotherapy (OIT) for milk allergy improved safety, but no significant clinical benefit was detected. OBJECTIVE: We sought to investigate mechanisms by which omalizumab modulates immunity in the context of OIT and to identify baseline biomarkers that predict subgroups of patients most likely to benefit from omalizumab. METHODS: Blood was obtained at baseline and multiple time points during a placebo-controlled trial of OIT for milk allergy in which subjects were randomized to receive omalizumab or placebo. Immunologic outcomes included measurement of basophil CD63 expression and histamine release and casein-specific CD4+ regulatory T-cell proliferation. Biomarkers were analyzed in relationship to measurements of safety and efficacy. RESULTS: Milk-induced basophil CD63 expression was transiently reduced in whole blood samples from both omalizumab- and placebo-treated subjects. However, IgE-dependent histamine release increased in washed cell preparations from omalizumab- but not placebo-treated subjects. No increase in regulatory T-cell frequency was evident in either group. Subjects with lower rates of adverse reactions, regardless of arm, experienced better clinical outcomes. Pre-OIT basophil reactivity positively associated with occurrence of symptoms during OIT, whereas the baseline milk IgE/total IgE ratio correlated with the likelihood of achieving sustained unresponsiveness. A combination of baseline basophil and serologic biomarkers defined a subset of patients in which adjunctive therapy with omalizumab was associated with attainment of sustained unresponsiveness and a reduction in adverse reactions. CONCLUSIONS: Combining omalizumab therapy with milk OIT led to distinct alterations in basophil reactivity but not T-cell responses. Baseline biomarkers can identify subjects most likely to benefit from adjunctive therapy with omalizumab.

Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults.

BACKGROUND: Peanut allergy is common, life-threatening, and without therapeutic options. We evaluated peanut epicutaneous immunotherapy (EPIT) by using Viaskin Peanut for peanut allergy treatment. OBJECTIVE: We sought to evaluate the clinical, safety, and immunologic effects of EPIT for the treatment of peanut allergy. METHODS: In this multicenter, double-blind, randomized, placebo-controlled study, 74 participants with peanut allergy (ages 4-25 years) were treated with placebo (n = 25), Viaskin Peanut 100 µg (VP100; n = 24) or Viaskin Peanut 250 µg (VP250; n = 25; DBV Technologies, Montrouge, France). The primary outcome was treatment success after 52 weeks, which was defined as passing a 5044-mg protein oral food challenge or achieving a 10-fold or greater increase in successfully consumed dose from baseline to week 52. Adverse reactions and mechanistic changes were assessed. RESULTS: At week 52, treatment success was achieved in 3 (12%) placebo-treated participants, 11 (46%) VP100 participants, and 12 (48%) VP250 participants (P = .005 and P = .003, respectively, compared with placebo; VP100 vs VP250, P = .48). Median change in successfully consumed doses were 0, 43, and 130 mg of protein in the placebo, VP100, and VP250 groups, respectively (placebo vs VP100, P = .014; placebo vs VP250, P = .003). Treatment success was higher among younger children (P = .03; age, 4-11 vs >11 years). Overall, 14.4% of placebo doses and 79.8% of VP100 and VP250 doses resulted in reactions, predominantly local patch-site and mild reactions (P = .003). Increases in peanut-specific IgG4 levels and IgG4/IgE ratios were observed in peanut EPIT-treated participants, along with trends toward reduced basophil activation and peanut-specific TH2 cytokines. CONCLUSIONS: Peanut EPIT administration was safe and associated with a modest treatment response after 52 weeks, with the highest responses among younger children. This, when coupled with a high adherence and retention rate and significant changes in immune pathways, supports further investigation of this novel therapy.

Care cascade structural intervention versus standard of care in the diagnosis and treatment of HIV in China: a cluster-randomized controlled trial protocol.

BACKGROUND: The high rate of attrition along the care cascade of infection with human immunodeficiency virus (HIV) results in lost opportunities to provide timely antiretroviral therapy (ART) and to prevent unnecessarily high mortality. This study aims to assess the effectiveness of a structural intervention, the one-stop ("One4All") strategy that streamlines China's HIV care cascade with the intent to improve testing completeness, ART initiation, viral suppression, and mortality. METHOD: A two-arm, cluster-randomized controlled trial was implemented in twelve county hospitals in Guangxi China to test the effectiveness of the One4All strategy (intervention arm) compared to the current standard of care (SOC; control arm). The twelve study hospitals were selected for homogeneity and allocated one-to-one to the intervention and control arms. All patients screening HIV positive in study hospitals were enrolled. Target study enrollment was 180 participants per arm, 30 participants per hospital. Basic demographic information was collected as well as HIV risk behavior and route of infection. In intervention hospitals, patients then went on to receive point-of-care CD4 testing and in-parallel viral load (VL) testing whereas patients in control hospitals progressed through the usual SOC cascade. The primary outcome measure was testing completeness within 30 days of positive initial HIV screening result. Testing completeness was defined as receipt of all tests, test results, and post-test counseling. The secondary outcome measure was ART initiation (receipt of first ART prescriptions) within 90 days of positive initial HIV screening result. Tertiary outcome measures were viral suppression (≤200 copies/mL) and all-cause mortality at 12 months. DISCUSSION: We expect that this first-ever, cluster-randomized controlled trial of a bundle of interventions intended to streamline the HIV care cascade in China (the One4All strategy) will provide strong evidence for the benefit of accelerating diagnosis, thorough clinical assessment, and ART initiation via an optimized HIV care cascade. We furthermore anticipate that this evidence will be valuable to policymakers looking to elevate China's overall HIV/AIDS response to meet the UNAIDS 90-90-90 targets and the broader, global goal of eradication of the HIV/AIDS epidemic. TRIAL REGISTRATION: ClinicalTrials.gov # NCT02084316 . (Registered on March 7, 2014).

A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy.

BACKGROUND: Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions and, even when successful, has limited long-term efficacy because benefits usually diminish when treatment is discontinued. OBJECTIVE: We sought to examine whether the addition of omalizumab to milk OIT reduces treatment-related reactions, improves outcomes, or both. METHODS: This was a double-blind, placebo-controlled trial with subjects randomized to omalizumab or placebo. Open-label milk OIT was initiated after 4 months of omalizumab/placebo with escalation to maintenance over 22 to 40 weeks, followed by daily maintenance dosing through month 28. At month 28, omalizumab was discontinued, and subjects passing an oral food challenge (OFC) continued OIT for 8 weeks, after which OIT was discontinued with rechallenge at month 32 to assess sustained unresponsiveness (SU). RESULTS: Fifty-seven subjects (7-32 years) were randomized, with no significant baseline differences in age, milk-specific IgE levels, skin test results, or OFC results. At month 28, 24 (88.9%) omalizumab-treated subjects and 20 (71.4%) placebo-treated subjects passed the 10-g "desensitization" OFC (P = .18). At month 32, SU was demonstrated in 48.1% in the omalizumab group and 35.7% in the placebo group (P = .42). Adverse reactions were markedly reduced during OIT escalation in omalizumab-treated subjects for percentages of doses per subject provoking symptoms (2.1% vs 16.1%, P = .0005), dose-related reactions requiring treatment (0.0% vs 3.8%, P = .0008), and doses required to achieve maintenance (198 vs 225, P = .008). CONCLUSIONS: In this first randomized, double-blind, placebo-controlled trial of omalizumab in combination with food OIT, we found significant improvements in measurements of safety but not in outcomes of efficacy (desensitization and SU).

Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy.

BACKGROUND: We previously reported the results of a randomized placebo-controlled study of egg oral immunotherapy (eOIT) in which 27.5% of subjects achieved sustained unresponsiveness (SU) after 2 years. Here we report the results of treatment through 4 years and long-term follow-up. OBJECTIVE: We sought to evaluate the efficacy and safety of eOIT in participants treated up to 4 years. METHODS: Children with egg allergy (5-18 years old) received eOIT (n = 40) for up to 4 years or placebo (n = 15) for 1 year or less. The key outcome was the percentage of subjects achieving SU by year 4. Safety and immunologic assessments were performed, and long-term follow-up questionnaires (LFQs) were administered after study conclusion (LFQ-1) and 1 year later (LFQ-2). RESULTS: Of 40 eOIT-treated subjects, 20 (50.0%) of 40 demonstrated SU by year 4. For those subjects still dosing during years 3 and 4, mild symptoms were present in 12 (54.5%) of 22 subjects. At the time of the LFQ, more subjects receiving eOIT (LFQ-1, 23/34 [68%]; LFQ-2, 21/33 [64%]) were consuming unbaked and baked egg versus placebo (LFQ-1, 2/11 [18%], P = .006; LFQ-2, 3/12 [25%], P = .04). Of subjects achieving SU, 18 (90%) of 20 completed the LFQ, with 18 (100%) of 18 reporting consumption of all forms of egg. When compared with subjects not achieving SU, subjects achieving SU had higher IgG4 values (P = .001) and lower egg skin prick test scores (P = .0002) over time and a lower median baseline ratio of egg-specific IgE to total IgE (1.1% vs 2.7%, P = .04). CONCLUSIONS: SU after eOIT is enhanced with longer duration of therapy and increases the likelihood of tolerating unbaked egg in the diet.

Ebola in the United States.

The ongoing epidemic of Ebola virus in West Africa and attendant cases described in other parts of the world has focused attention on this heretofore rare disease. In this brief opinion article, we provide a short primer on the epidemiology, pathogenesis, clinical manifestations, US-based hospital preparedness, vaccine and therapy development, and control of Ebola virus disease for noninfectious disease physicians.

Sublingual immunotherapy for peanut allergy: Long-term follow-up of a randomized multicenter trial.

BACKGROUND: We previously reported the initial results of the first multicenter, randomized, double-blind, placebo-controlled clinical trial of peanut sublingual immunotherapy (SLIT), observing a favorable safety profile associated with modest clinical and immunologic effects in the first year. OBJECTIVE: We sought to provide long-term (3-year) clinical and immunologic outcomes for our peanut SLIT trial. Key end points were (1) percentage of responders at 2 years (ie, could consume 5 g of peanut powder or a 10-fold increase from baseline), (2) percentage reaching desensitization at 3 years, (3) percentage attaining sustained unresponsiveness after 3 years, (4) immunologic end points, and (5) assessment of safety parameters. METHODS: Response to treatment was evaluated in 40 subjects aged 12 to 40 years by performing a 10-g peanut powder oral food challenge after 2 and 3 years of daily peanut SLIT therapy. At 3 years, SLIT was discontinued for 8 weeks, followed by another 10-g oral food challenge and an open feeding of peanut butter to assess sustained unresponsiveness. RESULTS: Approximately 98% of the 18,165 doses were tolerated without adverse reactions beyond the oropharynx, with no severe symptoms or uses of epinephrine. A high rate (>50%) discontinued therapy. By study's end, 4 (10.8%) of 37 SLIT-treated participants were fully desensitized to 10 g of peanut powder, and all 4 achieved sustained unresponsiveness. Responders at 2 years showed a significant decrease in peanut-specific basophil activation and skin prick test titration compared with nonresponders. CONCLUSIONS: Peanut SLIT induced a modest level of desensitization, decreased immunologic activity over 3 years in responders, and had an excellent long-term safety profile. However, most patients discontinued therapy by the end of year 3, and only 10.8% of subjects achieved sustained unresponsiveness.