Safety assessment of brodalumab: Real world adverse event analysis from the FAERS database

doi:10.21203/rs.3.rs-4719372/v1

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Safety assessment of brodalumab: Real world adverse event analysis from the FAERS database

https://doi.org/10.21203/rs.3.rs-4719372/v1

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Objective: This study aims to analyse adverse drug events (ADE) related to brodalumab from the first quarter of 2017 and the fourth quarter of 2023 from FAERS database.

Methods: The ADE data related to brodalumab from 2017 Q1 to 2023 Q4 were collected. After standardizing the data, a variety of signal quantification techniques, including ROR, PRR, BCPNN, and MGPS were used for analysis.

Results: Among the 6083 ADE reports with brodalumab as the primary suspected drug, 168 preferred terms (PT) of adverse reactions spanning 23 different system organ classes (SOC) were identified. Specifically, palmoplantar pustulosis(n = 8 , ROR 99.43, PRR 99.29, IC 6.6, EBGM 97.21), extranodal marginal zone b-cell lymphoma (malt type) (n = 3 , ROR 63.94, PRR 63.9, IC 5.98, EBGM 63.04)and calcium metabolism disorder(n = 3, ROR 259.37 , PRR 259.23 , IC 7.94 , EBGM 245.4) presented strong ADE signals, which aren't explicitly detailed in the drug's guidelines.

Conclusion: Although brodalumab offers significant therapeutic advantages, it is also associated with a range of adverse reactions. Clinicians should diligently monitor for the onset of palmoplantar pustulosis, extranodal marginal zone B-cell lymphoma (MALT type), disturbances in calcium metabolism, and other potential complications during its clinical use.

Biological sciences/Immunology

Health sciences/Diseases/Immunological disorders/Autoimmune diseases/Psoriasis

Brodalumab

Adverse drug reaction

Psoriasis

Biologics

Psoriasis is a chronic, relapsing, inflammatory, systemic disease that affects approximately 125 million people worldwide [1]. Psoriasis is characterized by distinct erythematous, scaly plaques on the skin that are unsightly, itchy, and painful [2]. Research has demonstrated that interleukin (IL)-17 is crucial in the pathogenesis of psoriasis. Consequently, therapies targeting IL-17 have proven to be effective in managing this condition.

Brodalumab (Siliq®; Valeant Pharmaceuticals) is a human IL-17RA IgG2 monoclonal antibody. Brodalumab, distinct from other IL-17 inhibitors, targets a subunit of the interleukin-17 receptor complex, thereby disrupting the downstream signaling pathways of interleukin-17 cytokines. Which means brodalumab can effectively inhibit the actions of IL-17A, IL-17C, and IL-17F[3]. Brodalumab, initially introduced in Japan in 2016, has subsequently received approval for the treatment of adults with moderate to severe plaque psoriasis in both the United States and the European Union. However, because of the relatively short time the drug has been on the market, safety data are still insufficient and there is some risk in terms of the drug's safety.

The U.S. FDA Adverse Event Reporting System (FAERS) database is an open, self-reporting drug safety monitoring system that provides some indication of the occurrence of drug-related adverse events (AEs) in the real world. The aim of this article is to examine brodalumab data in the FAERS database using multiple signal quantification techniques to evaluate the data from different angles and and provide useful information to ensure patient medication safety.

2.1.Data source

Since brodalumab was approved by FDA in February 15, 2017,reports submitted between the first quarter of 2017 and the fourth quarter of 2023 (the most recent update of the FAERS database at the time the study was conducted) were extracted for our study.

2.2.Data processing

We removed duplicate reports by following the FDA-recommended method, after extracting reports from the FAERS database. We selected the PRIMARYID and CASEID from the DEMO table and sorted them by CASEID and PRIMARYID. Data with fewer than 10 reports per quarter were also excluded. MedDRA was then used to correct the preferred term (PT) names in the FAERS database and to obtain the system organ class (SOC) and preferred terms (PTs). These reports contain various information, such as the date of the report, the age and gender of the patient, the reporting person and the reporting country. Serious outcomes are life-threatening events or events that result in hospitalization, injury or death.

2.3Data analysing

Statistical analysis Based on the rationale of disproportionality analysis and Bayesian analysis, we employed the reporting odds ratio (ROR)[4], proportional reporting ratio (PRR)[5], Bayesian confidence propagation neural network (BCPNN)[6], and multi-item gamma Poisson shrinker (MGPS)[7] algorithms to investigate the associations between the drug and the specified AEs. All the above methods are based on the parameters of the signal detection 2×2 table, the 2×2 table is shown in Table 1, and the equations and criteria for the four algorithms are listed in Table 2.

Table 1

Four grid table
	brodalumab related ADEs	Non-brodalumab related ADEs	Total
brodalumab	a	b	a + b
Non-brodalumab	c	d	c + d
Total	a + c	b + d	N = a + b + c + d

Table 2

ROR, PRR, BCPNN, and EBGM methods, equation, and criteria.
Algorithms	Equation	Criteria
ROR	ROR=(a/b)/(c/d)	lower·limit·of 95%CI > 1 ,N > 3
ROR	95%CI = e^{ln(ROR)±1.96(1/a+1/b+1/c+1/d)^0.5}	lower·limit·of 95%CI > 1 ,N > 3
PRR	PRR=[a/(a + c)]/[b/(b + d)]	PRR > 2, x² > 4, N > 3
PRR	χ²= [(ad-bc)^2](a + b + c + d)/[(a + b)(c + d)(a + c)(b + d)]	PRR > 2, x² > 4, N > 3
BCPNN	IC = log₂a(a + b + c + d)(a + c)(a + b)	IC025 > 0
BCPNN	95%CI = E(IC) ± 2V(IC)^0.5	IC025 > 0
MGPS	EBGM = a(a + b + c + d)/[(a + c)(a + b)]	EBGM05 > 2
MGPS	95%CI = e^{ln(EBGM)±1.96(1/a+1/b+1/c+1/d)^0.5}	EBGM05 > 2

3.1.Basic characteristics of Brodalumab-related ADEs

From the third quarter of 2018 to the fourth quarterof 2023, this study obtained a total of 6083 adverse event reports from the FAERS database. Among these, there were 1480 reports where Brodalumab was identified as the primary suspected drug for the adverse drug event (ADE). And the basic characteristics were presented in Table 3. TThe data indicated a general upward trend in reports over the years, likely attributed to the widespread adoption of brodalumab. Notably, brodalumab-associated incidents were more prevalent in male patients compared to female patients (55.54% vs. 42.43%). The majority of reports pertained to individuals aged 18–65 years (54.53%), with a significant portion also involving elderly patients over 60 years (25.74%). Only one report was in patients aged below 18 years.

The most reported indication was psoriasis (76.52%), followed by psoriatic arthropathy (3.58%), pustular psoriasis (2.09%), hidradenitis (0.61%), erythrodermic psoriasis (0.47%) and ankylosing spondylitis(0.40%). Regarding the report country, United States (28.31%) submitted most reports, followed by Canada (27.77%), Japan (14.32%), Germany (7.84%), and United kindom (6.82%), respectively. The most frequently reported severe outcomes were OS (57.64%) and HO (31.29%).

Table 3

Basic information on ADEs related to Brodalumab from the FAERS database.
variable	Total(%)
Year
2018	146( 9.86)
2019	291(19.66)
2020	225(15.20)
2021	220(14.86)
2022	274(18.51)
2023	324(21.89)
Sex
female	628(42.43)
male	822(55.54)
unkown	30( 2.03)
Age(years)
<18	1( 0.07)
18 ~ 45	276(18.65)
45 ~ 65	531(35.88)
>=65	381(25.74)
unknow	291(19.66)
Indications(top six)
psoriasis	1134(76.52)
psoriatic arthropathy	53( 3.58)
pustular psoriasis	31( 2.09)
hidradenitis	9( 0.61)
erythrodermic psoriasis	7( 0.47)
ankylosing spondylitis	6( 0.40)
Outcomes
other serious outcomes(OS)	886(57.64)
Hospitalization(HO)	481(31.29)
death	93( 6.05)
disability	45( 2.93)
life threatening	32( 2.08)
Reported countries(top five)
United States	419(28.31)
Canada	411(27.77)
Japan	212(14.32)
Germany	116( 7.84)
United Kingdom	101( 6.82)

3.2.Brodalumab signal mining

Adverse reactions related to brodalumab involved 23 SOCs. The study showed that the three most frequent systems were skin and subcutaneous tissue disorders (n = 662, ROR 2.06, PRR 1.93, IC 0.95, EBGM 1.93), infections and infestations (n = 583, ROR 1.93, PRR 1.83, IC 0.87, EBGM 1.83), and musculoskeletal and connective tissue disorders (n = 534, ROR 1.9, PRR 1.81, IC 0.86, EBGM 1.81), consistent with Brodalumab's characteristics as a Dermatologic drugs. Details can be found in Table 4.

Table 4 The signal strength of ADEs of Brodalumab at the SOC level in FAERS database

soc	Case Reports	ROR(95% CI)	PRR(95% CI)	IC(IC025)	EBGM(EBGM05)
skin and subcutaneous tissue disorders	662	2.06(1.9, 2.23)	1.93(1.78, 2.09)	0.95(0.83)	1.93(1.8)
infections and infestations	583	1.93(1.77, 2.1)	1.83(1.69, 1.98)	0.87(0.75)	1.83(1.71)
musculoskeletal and connective tissue disorders	534	1.9(1.73, 2.07)	1.81(1.67, 1.96)	0.86(0.73)	1.81(1.68)
general disorders and administration site conditions	1035	1.02(0.95, 1.09)	1.02(0.96, 1.08)	0.02(-0.07)	1.02(0.96)
psychiatric disorders	305	0.97(0.87, 1.09)	0.97(0.86, 1.09)	-0.04(-0.2)	0.97(0.88)
injury, poisoning and procedural complications	629	0.94(0.86, 1.02)	0.94(0.87, 1.02)	-0.08(-0.2)	0.94(0.88)
hepatobiliary disorders	45	0.94(0.7, 1.26)	0.94(0.7, 1.26)	-0.09(-0.51)	0.94(0.73)
eye disorders	98	0.89(0.73, 1.08)	0.89(0.73, 1.08)	-0.17(-0.46)	0.89(0.75)
gastrointestinal disorders	387	0.83(0.74, 0.92)	0.84(0.76, 0.93)	-0.25(-0.4)	0.84(0.77)
ear and labyrinth disorders	20	0.82(0.53, 1.28)	0.82(0.53, 1.26)	-0.28(-0.9)	0.82(0.57)
cardiac disorders	96	0.81(0.67, 1)	0.82(0.67, 1)	-0.29(-0.58)	0.82(0.69)
vascular disorders	84	0.77(0.62, 0.95)	0.77(0.62, 0.96)	-0.38(-0.69)	0.77(0.64)
respiratory, thoracic and mediastinal disorders	193	0.72(0.63, 0.84)	0.73(0.64, 0.84)	-0.45(-0.65)	0.73(0.65)
nervous system disorders	313	0.7(0.63, 0.79)	0.72(0.65, 0.79)	-0.48(-0.64)	0.72(0.65)
immune system disorders	47	0.66(0.49, 0.87)	0.66(0.49, 0.89)	-0.6(-1.01)	0.66(0.52)
neoplasms benign, malignant and unspecified (incl cysts and polyps)	128	0.61(0.52, 0.73)	0.62(0.52, 0.74)	-0.68(-0.93)	0.62(0.54)
metabolism and nutrition disorders	70	0.61(0.48, 0.78)	0.62(0.49, 0.78)	-0.69(-1.03)	0.62(0.51)
investigations	210	0.61(0.53, 0.7)	0.63(0.55, 0.72)	-0.68(-0.87)	0.63(0.56)
reproductive system and breast disorders	21	0.57(0.37, 0.87)	0.57(0.37, 0.88)	-0.81(-1.41)	0.57(0.4)
pregnancy, puerperium and perinatal conditions	10	0.45(0.24, 0.85)	0.46(0.25, 0.86)	-1.13(-1.99)	0.46(0.27)
renal and urinary disorders	51	0.42(0.32, 0.55)	0.42(0.32, 0.55)	-1.25(-1.64)	0.42(0.33)
endocrine disorders	6	0.4(0.18, 0.89)	0.4(0.18, 0.89)	-1.32(-2.39)	0.4(0.21)
blood and lymphatic system disorders	29	0.29(0.2, 0.42)	0.3(0.21, 0.44)	-1.75(-2.27)	0.3(0.22)

On the PT level,this study employed four algorithms to analyze drug adverse reactions, a positive signal is defined as long as one of the algorithmic criteria is met, resulting in 168 PTs. Ranked based on the strictest EBGM algorithm, the top 30 PTs are displayed in Table 5. Results revealed PTs with high signal strength, such as vaccination site vesicles (n = 4, ROR 2291.56, PRR 2289.91, IC 10.58, EBGM 1526.94), vaccination site haemorrhage (n = 4, ROR 632.15, PRR 631.7, IC 9.12, EBGM 555.25), and calcium metabolism disorder (n = 3, ROR 259.37, PRR 259.23, IC 7.94, EBGM 245.4). Screening and excluding product problems, various types of injuries, poisoning and surgical complications, and possible clinical manifestations of the disease itself, the top 5 most frequent PTs are headache,depression, suicidal ideation, cellulitis, blood pressure increased. This study identified several infrequent yet significant adverse effects, including palmoplantar pustulosis, extranodal marginal zone B-cell lymphoma (MALT type), and calcium metabolism disorders. Despite their rarity, the signal strength of these side effects was notably high. Details can be found in Table 5.

Table 5 The top 30 signal strength of adverse events of Brodalumab ranked by EBGM at the PTs level in FAERS database.

soc	pt	Case Reports	ROR(95% CI)	PRR(95% CI)	chisq	IC(IC025)	EBGM(EBGM05)
general disorders and administration site conditions	vaccination site vesicles	4	2291.56(689.83, 7612.33)	2289.91(692.75, 7569.39)	6101.09	10.58(9.09)	1526.94(559.19)
general disorders and administration site conditions	vaccination site haemorrhage	4	632.15(222.16, 1798.78)	631.7(223.55, 1785.07)	2213.5	9.12(7.76)	555.25(231.46)
metabolism and nutrition disorders	calcium metabolism disorder	3	259.37(81.03, 830.28)	259.23(81.56, 823.95)	730.38	7.94(6.48)	245.4(92.7)
investigations	psoriasis area severity index increased	4	205.98(75.62, 561.11)	205.83(75.75, 559.28)	780.29	7.62(6.32)	197.02(85.18)
general disorders and administration site conditions	vaccination site erythema	3	112.68(35.83, 354.35)	112.62(36.13, 351.01)	323.92	6.78(5.34)	109.94(42.15)
skin and subcutaneous tissue disorders	palmoplantar pustulosis	8	99.43(49.33, 200.42)	99.29(49.03, 201.07)	761.91	6.6(5.65)	97.21(54.07)
skin and subcutaneous tissue disorders	erythrodermic psoriasis	4	67.65(25.2, 181.61)	67.6(25.37, 180.12)	258.64	6.06(4.78)	66.63(29.16)
neoplasms benign, malignant and unspecified (incl cysts and polyps)	extranodal marginal zone b-cell lymphoma (malt type)	3	63.94(20.45, 199.88)	63.9(20.5, 199.16)	183.21	5.98(4.55)	63.04(24.29)
infections and infestations	tinea pedis	7	56.02(26.57, 118.09)	55.95(26.57, 117.83)	373.22	5.79(4.78)	55.29(29.62)
skin and subcutaneous tissue disorders	pustular psoriasis	12	49.62(28.07, 87.69)	49.51(28.04, 87.41)	564.31	5.61(4.82)	48.99(30.42)
gastrointestinal disorders	coating in mouth	3	49.1(15.73, 153.2)	49.07(15.74, 152.94)	139.77	5.6(4.18)	48.56(18.74)
injury, poisoning and procedural complications	paternal exposure during pregnancy	4	32.85(12.28, 87.87)	32.83(12.32, 87.47)	122.57	5.03(3.76)	32.6(14.31)
general disorders and administration site conditions	symptom recurrence	17	21.82(13.54, 35.17)	21.76(13.59, 34.83)	335.15	4.44(3.77)	21.66(14.53)
musculoskeletal and connective tissue disorders	psoriatic arthropathy	95	21.41(17.47, 26.24)	21.06(17.31, 25.62)	1808.68	4.39(4.1)	20.97(17.69)
skin and subcutaneous tissue disorders	psoriasis	283	21.32(18.91, 24.04)	20.29(18.04, 22.82)	5179.66	4.34(4.16)	20.2(18.28)
musculoskeletal and connective tissue disorders	dactylitis	3	20.19(6.49, 62.76)	20.18(6.47, 62.9)	54.44	4.33(2.91)	20.09(7.78)
infections and infestations	oral fungal infection	4	18.37(6.88, 49.06)	18.36(6.89, 48.92)	65.38	4.19(2.92)	18.29(8.04)
neoplasms benign, malignant and unspecified (incl cysts and polyps)	cholangiocarcinoma	3	17.06(5.49, 53.01)	17.05(5.47, 53.14)	45.15	4.09(2.67)	16.99(6.58)
psychiatric disorders	mental fatigue	3	16.46(5.3, 51.16)	16.45(5.28, 51.27)	43.39	4.04(2.62)	16.4(6.35)
musculoskeletal and connective tissue disorders	limb mass	5	15.99(6.64, 38.5)	15.98(6.61, 38.6)	69.97	3.99(2.84)	15.93(7.64)
skin and subcutaneous tissue disorders	skin weeping	5	15.95(6.63, 38.39)	15.94(6.6, 38.51)	69.75	3.99(2.83)	15.88(7.62)
infections and infestations	skin infection	17	15.05(9.34, 24.25)	15.01(9.38, 24.03)	221.62	3.9(3.23)	14.96(10.04)
respiratory, thoracic and mediastinal disorders	pleurisy	6	13.82(6.2, 30.8)	13.8(6.18, 30.82)	71.04	3.78(2.71)	13.76(7.04)
neoplasms benign, malignant and unspecified (incl cysts and polyps)	lung adenocarcinoma	4	13.73(5.14, 36.65)	13.72(5.15, 36.56)	47.04	3.77(2.51)	13.68(6.02)
skin and subcutaneous tissue disorders	skin atrophy	7	12.76(6.07, 26.8)	12.74(6.05, 26.83)	75.54	3.67(2.67)	12.71(6.83)
investigations	thyroid function test abnormal	4	12.14(4.55, 32.4)	12.13(4.55, 32.32)	40.75	3.6(2.33)	12.1(5.32)
infections and infestations	oral candidiasis	13	11.93(6.92, 20.57)	11.9(6.87, 20.6)	129.49	3.57(2.81)	11.87(7.52)
injury, poisoning and procedural complications	intentional dose omission	35	11.89(8.52, 16.58)	11.82(8.47, 16.49)	345.96	3.56(3.09)	11.79(8.93)
general disorders and administration site conditions	disease recurrence	70	11.71(9.25, 14.83)	11.58(9.15, 14.65)	675.43	3.53(3.19)	11.55(9.48)
eye disorders	uveitis	17	11.22(6.97, 18.08)	11.19(6.99, 17.91)	157.45	3.48(2.81)	11.17(7.49)

Despite the well-documented benefits of biological agents for psoriasis relief, serious and unexpected adverse drug reactions also have been reported[8]. Thus, there is a need to monitor their actual use and adverse effects to ensure their safety and efficacy.

By delving the FAERS database from the first quarter of 2017 to the fourth quarter of 2023, this study systematically assessed the adverse reactions associated with Brodalumab, reaffirming established safety data while identifying new potential risks. These findings offer a more comprehensive and precise dataset to support clinical practice and inform public health decisions. An in-depth discussion of the study's results is presented below.

Male patients were more prevalent than female patients, This may be related to the tendency of males to report adverse events more frequently,because there is no gender difference in the incidence of psoriasis[9]. It should be noted that much of the data lacked specific age-specific data, which limits our understanding of the occurrence of side effects in different age groups. Accurate age-specific data and examination of differences in drug reactions across age groups are needed for further research.

As a dermatologic drugs, the adverse events of brodalumab predominantly concern skin and subcutaneous tissue disorders, infections and infestations and musculoskeletal and connective tissue disorders.At the PT level, apart from the high incidence of vaccination site vesicles and vaccination site haemorrhage, this study also discovered adverse events not mentioned in the medication leaflet, such as palmoplantar pustulosis, extranodal marginal zone b-cell lymphoma (malt type) and calcium metabolism disorder. This suggests the value of quantitative signal detection methods in monitoring adverse drug events to provide information about potential risks. Palmoplantar pustulosis, extranodal marginal zone b-cell lymphoma (malt type) and calcium metabolism disorder have strong signal strengths and warrant special attention.

Palmoplantar pustulosis (PPP) is a chronic inflammatory disease characterized by aseptic pustules on the palms and metatarsals, with many similarities to pustular psoriasis, and has been regarded by many scholars as an extremity variant of pustular psoriasis with limb restriction, whereas some scholars consider PPP to be a separate disease[10]. In addition, cases of palmoplantar pustulosis caused by brodalumab have been reported[11].It is speculated that blockade of IL-17A might lead to an increased production of inflammatory cytokines upstream of IL-17A or that the Th1 pathway for cytokines such as IL-12 and TNF is upregulated and may mediate this paradoxical response[12].

Marginal zone lymphomas (MZL) represent the second most prevalent subtype of indolent lymphomas, constituting 7% of all non-Hodgkin lymphomas (NHL). In 2016, there were 7,460 new cases diagnosed in the United States.[13–14]. Extranodal marginal zone b-cell lymphoma is one of the MZL subtypes[15].Psoriasis is associated with an increased incidence of certain cancers, and patients with psoriasis have an increased risk of developing lymphohematopoietic and pancreatic cancers and other malignant tumors, and the risk is further elevated in patients with a long history of the disease[16], which may be related to impaired immune function [17]. The results of the our study suggest that brodalumab does not have any clear link with the incidence of benign, malignant, and tumors of undetermined nature, but has a higher signal intensity with the development of extranodal marginal zone b-cell lymphomas. It seems that brodalumab has a low risk of carcinogenesis based on the available data, but more studies are needed to confirm this.

Recent studies have increasingly highlighted that individuals with psoriasis may face a heightened risk of pathologic fractures and osteoporosis[18], and many reports have shown that patients with psoriasis have serum vitamin D deficiency or insufficiency, and several clinical case-control studies have shown that patients with psoriasis have significantly lower levels of serum 25(OH)D compared to controls, and have reported that serum 25(OH)D levels correlate with disease severity in a A negative correlation between serum 25(OH)D levels and disease severity has been reported[19]. Vitamin D has a regulatory effect on calcium metabolism, promoting intestinal absorption of calcium, calcium deposition in osteoblasts, and renal reabsorption of calcium[20]. Therefore, it cannot be confirmed that the calcium metabolism disorder in this study was caused by brodalumab.

It is important to recognize that the incidence of side effects is influenced by numerous factors, including the characteristics of the drug, individual variability, and underlying health conditions. Additionally, certain limitations must be considered, such as the reliance on spontaneous reports, which can result in reporting bias and incomplete data. Consequently, more extensive experimental and clinical research is necessary to understand the mechanisms underlying adverse events. To achieve a more comprehensive and accurate understanding, future research should incorporate detailed prospective studies that integrate clinical trials with epidemiological analyses to more precisely evaluate the safety risks associated with brodalumab.

In summary, this study provides a solid scientific basis for assessing the safety of budalumab through a multifaceted, multilevel analysis. The study also identified several specific adverse reactions not explicitly mentioned in the package leaflet, such as palmoplantar pustulosis, b-cell lymphoma of the extranodal marginal zone (malleolar type) and calcium metabolism disorders. Although these are relatively rare, they are highly indicative and require more attention and research. These findings suggest that Clinicians should be more cautious when administering budalumab treatment and patients should be aware of these potential side effects. Despite the limitations of the data, these preliminary results will undoubtedly provide valuable support for further research and safety regulation in the future. In particular, some newly identified potential risks should be of great concern to the medical community and regulatory authorities.

Aacknowledgements

Funding for this study was provided by [Fund Project] Beijing Natural Science Foundation (grant number 7232288).

Conflict of interest

The authors declare that they have no competing interests.

Author’s contributions

Yue Wan and Yang Zhou wrote the manuscript and generated figures. Wenjin Chen, Huanhuan Li and Jingjing Huang contributed to editing the manuscript. Jianhong Li supervised the study and approved the submission of this article. All authors read and approved the final manuscript.

Data availability

The dataset generated during and analyzed during the current study are available from the corresponding author on reasonable request.

Armstrong AW,Read C.Pathophysiology,clinical presentation,and treatment of psoriasis:a review[J].JAMA,2020,323(19):1945-1960. https://doi.org/10.1001/jama.2020.4006.
Boehncke WH, Schon MP. Psoriasis. Lancet.2015 Sep 5;386(9997):983–94. https://doi.org/10.1016/S0140-6736(14)61909-7.
Galluzzo M, D’Adamio S, Massaro A, et al. Spotlight on brodalumabin the reatment of plaque psoriasis: the evidence to date. ClinCosmet Investig Dermatol.2019;12:311–321. https://doi.org/10.2147/CCID.S165605
Rothman KJ, Lanes S, Sacks ST. The reporting odds ratio and its dvantages over the proportional reporting ratio. Pharmacoepidemiol Drug Saf. 2004 Aug;13(8):519-23. https://doi.org/10.1002/pds.1001
Evans SJ, Waller PC, Davis S. Use of proportional reporting ratios (PRRs) or signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiol Drug Saf. 2001 Oct-Nov;10(6):483-6. https://doi.org/10.1002/pds.677.
Bate A, Lindquist M, Edwards IR, Olsson S, Orre R, Lansner A, De Freitas RM. A Bayesian neural network method for adverse drug reaction signal generateon. Eur J Clin Pharmacol. 1998 Jun;54(4):315-21. https://doi.org/10.1007/s002280050466.
DuMouchel, W. Bayesian data mining in large frequency tables, with an application to the FDA spontaneous reporting system[J]. Am. Stat. 1999,53 (3):177–190.
Boyman O, Comte D, Spertini F. Adverse reactions to biologic agents and their medical management. Nat. Rev. Rheumatol. 2014;10:612–627.https://doi.org/10.1038/nrrheum.2014.123
Parisi R, Symmons DP, Griffiths CE, Ashcroft DM; Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013 Feb;133(2):377-85. https://doi.org/10.1038/jid.2012.339
Yamamoto T. Similarity and difference between palmoplantar pustulosis and pustular psoriasis. J Dermatol, 2021, 1346-8138. https://doi.org/10.1111/1346-8138.15826.
Mössner R,Pinter A. Paradoxical palmoplantar pustulosis induced by secukinumab and brodalumab: a report of three cases[J]. Eur J Dermatol,2020,30(2) : 177-209. https://doi.org/10.1684/ejd.2020.3702.
Dogra S, Bishnoi A, Narang T, Handa S. Secukinumab-induced paradoxical pustular psoriasis. Clin Exp Dermatol. 2019 Jan;44(1):72-73. https://doi.org/10.1111/ced.13731.
Reid R, Friedberg JW. Management of marginal zone lymphoma. Oncology (Williston Park). 2013; 27: 840-842. 844.
Sriskandarajah P, Dearden CE. Epidemiology and environmental aspects of marginal zone lymphomas. Best Pract Res Clin Haematol. 2017; 30: 84-91. https://doi.org/10.1016/j.beha.2016.07.002.
Cheah CY, Seymour JF. Marginal zone lymphoma: 2023 update on diagnosis and management. Am J Hematol. 2023 Oct;98(10):1645-1657. https://doi.org/10.1002/ajh.27058.
Brauchli Y B,Jick S S,Miret M，et al. Psoriasis and risk of incident cancer: an inception cohort study with a nested case-control analysis[J]. J Invest Dermatol,2009,129 ( 11) : 2604-2612. https://doi.org/10.1038/jid.2009.113.
Pouplard C,Brenaut E,Horreau C,et al. Risk of cancer in psoriasis: a systematic review and meta-analysis of epidemiological studies[J],J Eur Acad Dermatol Venereol,2013,27( s3) : 36-46. https://doi.org/10.1111/jdv.12165.
Muñoz-Torres M, Aguado P, Daudén E, Carrascosa JM, Rivera R. Osteoporosis and Psoriasis. Actas Dermosifiliogr (Engl Ed). 2019 Oct;110(8):642-652. English, Spanish. https://doi.org/10.1016/j.ad.2019.02.005.
Formisano E, Proietti E, Borgarelli C, Pisciotta L. Psoriasis and Vitamin D: A Systematic Review and Meta-Analysis. Nutrients. 2023 Jul 30;15(15):3387. https://doi.org/10.1016/j.ad.2019.02.005.
Kulda V. Metabolizmus vitaminu D [Vitamin D metabolism]. Vnitr Lek. 2012 May;58(5):400-4. Czech. PMID: 22716179.

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Safety assessment of brodalumab: Real world adverse event analysis from the FAERS database

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Version 1

Abstract

1. Introduction

2. Methods

2.1.Data source

2.2.Data processing

2.3Data analysing

3. Results

3.1.Basic characteristics of Brodalumab-related ADEs

3.2.Brodalumab signal mining

4. Discussion

5. Conclusion

Declarations

References

Additional Declarations

Status:

Version 1