Sex: U
Vaccine: MNQ, TDAP
Symptoms: Death, Failure to thrive
Clinical narrative: Death NOS; Failure to thrive; This case was reported in a literature article and described the occurrence of unknown cause of death in a adult patient who received DTPa (Reduced antigen) (Boostrix) for prophylaxis.   Co-suspect products included MENACTRA (batch number UNK, expiry date unknown) for prophylaxis and tralokinumab (batch number UNK, expiry date unknown) for atopic dermatitis.   Concurrent medical conditions included atopic dermatitis (Moderate-to-severe).   On an unknown date, the patient received Boostrix (intramuscular), MENACTRA (intramuscular) and tralokinumab 600 mg once daily (600 mg daily). On an unknown date, the dose was changed to 300 mg once daily (300 mg daily). On an unknown date, unknown after receiving Boostrix, the patient experienced unknown cause of death (serious criteria death and GSK medically significant) and failure to thrive (serious criteria GSK medically significant and other: serious as per reporter). The action taken with tralokinumab was unknown. On an unknown date, the outcome of the unknown cause of death was fatal and the outcome of the failure to thrive was unknown. The reported cause of death was unknown cause of death.   It was unknown if the reporter considered the unknown cause of death and failure to thrive to be related to Boostrix.  Additional details were provided as follows: This case was reported in a literature article and described the occurrence of failure to thrive in a patient aged between 18-54 years old of unspecified gender, who was vaccinated with Boostrix (GlaxoSmithKline) for prophylaxis. The patient was a part of the phase 2, double-blind, randomized, placebo controlled, 30-week trial that objective was to assess immune responses to standard vaccines in tralokinumab-treated adults with moderate-to-severe atopic dermatitis (AD). [The objective of this study was to demonstrate non-inferiority of tralokinumab versus placebo with respect to immune responses of two concomitantly administered, non-live vaccines. The study also aimed to assess efficacy, safety, and tolerability of tralokinumab treatment with concomitantly administered vaccines. ECZTRA 5 (NCT03562377) was a phase 2, double-blind, randomized, placebo controlled, 30-week trial. Eligible adults were randomized 1:1 (tralokinumab 300 mg or placebo, 107:108 every 2 weeks [q2w] for 16 weeks), receiving Tdap (tetanus/diphtheria/pertussis) and meningococcal vaccines at week 12. Primary endpoints were positive anti-tetanus and anti-meningococcal responses (week 12-week 16; non-inferiority margin, -25%; responder, more than 3-fold immunoglobulin-G increase). The study enrolled patients with moderate-to-severe AD, aged 18-54 years, who were candidates for systemic therapy and had a recent (within 1 year) history of inadequate response to topical treatments or for whom topical treatments were medically inadvisable. Other key inclusion criteria included a diagnosis of AD for more than or equal to 1 year, AD involvement of more than or equal to 10% body surface area at screening and baseline, Eczema Area and Severity Index (EASI) more than or equal to 12 at screening and more than or equal to 16 at baseline, and Investigator's Global Assessment (IGA) more than or equal to 3 at screening and baseline. Patients were excluded if administration of either vaccine was contraindicated or medically inadvisable or if they had received any vaccine (except influenza virus vaccines) within 3 months prior to screening, any meningococcal vaccine within 1 year prior to screening, or any tetanus-, diphtheria-, or pertussis-containing vaccine within 5 years prior to screening. Patients were recruited from 11 sites in country and 35 sites in the country by the site's investigator]. In this patient, administration of the tetanus, diphtheria, and pertussis vaccine provided in this trial was not contraindicated or medically inadvisable. No information on patient's medical history, family history, concurrent condition or concomitant medication was provided. On an unspecified date, the patient received one dose of Boostrix (Tdap: tetanus, diphtheria, and acellular pertussis) and one dose of Menactra (meningococcal vaccine) administered intramuscularly in the deltoid muscle of the upper arm (one vaccine in each arm), before tralokinumab (batch number not provided for both). The patient randomized to tralokinumab received 300 mg every 2 weeks [q2w] for 16 weeks after initial loading dose (600 mg) on day 0 (baseline). The age of vaccination was not provided. [All patients randomized to tralokinumab received an initial loading dose of 600 mg on day 0 (baseline). At week 12, patients received one dose of combined tetanus, diphtheria, and acellular pertussis (Tdap; Boostrix) vaccine and one dose of meningococcal vaccine (Menactra), administered intramuscularly in the deltoid muscle of the upper arm (one vaccine in each arm), before tralokinumab or placebo injections, and in accordance with local labeling. These vaccines were chosen as they are both common inclusions in country-wide vaccination schedules, and represent different antigen structures (protein and polysaccharide)]. On an unspecified date, an unknown period after the vaccination, the patient had eight serious adverse events (SAEs) within the safety follow-up period. Five of these SAEs contributed to a fatal outcome for this patient. All eight SAEs were assessed as being unrelated to the investigational medicinal product (IMP). An additional SAE reported in the same patient during the treatment period was failure to thrive; also had a fatal outcome and was considered as possibly related to treatment by the investigator. [At week 16, non-inferiority of tralokinumab versus placebo for immune responses to Tdap (91.9% vs 96.1%) and meningococcal (86.0% vs 84.2%) vaccines was demonstrated. During treatment, adverse-event rates were lower for tralokinumab versus placebo; most events were mild or moderate. The primary endpoints were positive anti-tetanus and anti-meningococcal responses from weeks 12-16. A positive anti-tetanus response was defined as having at least a three-fold immunoglobulin (Ig) G increase compared to week 12 if IgG less than or equal to 1.0 IU/mL at week 12 or IgG more than or equal to 2.5 IU/mL if IgG more than 1.0 IU/mL at week 12. A positive anti-meningococcal response was defined as IgG more than or equal to 3.0 mcg/mL with at least a three-fold increase compared to week 12, in three of the four assays used (for each meningococcal subtype included in the vaccine: A, C, W, and Y). Secondary endpoints aimed to assess the efficacy, safety, and tolerability of tralokinumab alongside vaccine administration, using the full analysis set. Upon completing the 16-week treatment period, eligible patients were invited to enter an open-label, long-term, extension trial of tralokinumab under a separate trial protocol (ECZTEND, NCT03587805); patients who used rescue medication in ECZTRA 5 were still eligible for inclusion in ECZTEND. Otherwise, patients were required to complete a 14-week, off-treatment, safety follow-up period. The rate of AEs, the number of moderate AEs, and the number of SAEs were higher in the tralokinumab group compared with the placebo group; this difference was driven by a single patient, in whom 18 of the 24 AEs were reported. The overall rate of AEs in the safety follow-up period was lower in the tralokinumab group versus the placebo group (69.59 vs 118.3 events per 100 patient-years' follow-up, respectively). Overall, 11 SAEs were reported in the safety follow-up period in four patients (two in each treatment group), with more events for tralokinumab (nine) compared with placebo (two). The higher rate in the tralokinumab group was driven by the single patient, in whom eight of the nine SAEs within the safety follow-up period occurred; five of these SAEs contributed to a fatal outcome for this patient. All eight SAEs were assessed as being unrelated to the IMP. An additional SAE reported in the same patient during the treatment period ("failure to thrive") also had a fatal outcome and was considered as possibly related to treatment by the investigator].  On an unspecified date, the patient was died with an unknown cause. It was unknown whether the patient's autopsy was performed or not. This case has been considered serious due to death. The author commented, "The investigator did not believe that tralokinumab was the cause of the SAE, but due to their limited experience with tralokinumab in humans, a causal relationship for such a general symptom as weight loss could not be entirely ruled out. All SAEs reported in this patient were not considered related to tralokinumab by the study sponsor, based on the patient's medical history and concomitant medications. These results indicate that tralokinumab 300 mg every 2 weeks treatment did not affect the immune responses to Tdap or meningococcal vaccines, with vaccine-induced immune response rates within expected ranges. For both vaccines, the 95% CI for treatment differences were within the pre-specified -25% noninferiority margin, thereby demonstrating the noninferiority of tralokinumab compared with placebo with respect to immune responses to each concomitantly administered vaccine. Additionally, tralokinumab was safe and well tolerated when administered concomitantly with the selected vaccines, with a safety profile comparable to three phase 3 trials. In this phase 2 study, the treatment difference versus placebo was similar to that seen in the larger ECZTRA 1 and 2 monotherapy trials, further substantiating the robust efficacy reported at week 16 and over 52 weeks in these phase 3 trials. The results of this study indicate that tralokinumab's specific neutralization of IL-13 does not affect the immune response to concomitantly administered Tdap and meningococcal vaccines, suggesting that standard, non-live vaccines are effective and can be safely prescribed in tralokinumab-treated adults with moderate-to-severe AD without the need for tralokinumab interruption. The effect of tralokinumab on vaccines against viral-borne diseases (such as influenza), however, was not examined, which may be an area for future study to inform vaccination programs and guidelines. In this study, data supports noninferiority of tralokinumab versus placebo for vaccine-induced immune responses to Tdap (91.9% vs 96.1%) and meningococcal (86.0% vs 84.2%) vaccines." The author concluded, "Tralokinumab 300 mg q2w treatment did not affect immune responses to Tdap and meningococcal vaccines, and was well tolerated when administered concomitantly, with safety profile comparable to phase 3 trials."; Reported Cause(s) of Death: unknown cause of death