Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

Table 1 Demographic characteristics and the use of medication (n = 843)

	Males1n (%)	Females1	P value2
Males/females (%males)	386 (46)	457
Age (mean, range), yr	43 (16-87)	42 (18-87)	0.138
Duration of the disease (mean, range)	14 (0-48)	14 (0-54)	0.168
CD/UC/unclassified	233 (40)/141 (58)/12 (57)	345/103/9	< 0.0001
Immunosuppressive agents	265 (45)	321	0.652
Thiopurines	247 (45)	299	0.665
Methotrexate	73 (42)	103	0.203
Cyclosporine	26 (57)	20	0.170
Tacrolimus	0	1
Anti-TNF	101 (42)	139	0.193
Infliximab	93 (41)	134	0.102
Adalimumab	39 (41)	60	0.328
Certolizumab	1 (20)	4	0.401

¹For each categorical variable number and percentage of males within the group is displayed; ²Pvalues for test of the sex-related differences; two-sidedχ²test for categorical variables andt-test for continuous variables. Anti-TNF: Anti-tumor necrosis factor agents; CD: Crohn’s disease; UC: Ulcerative colitis.

Table 2 Categories of adverse drug reactions to immunosuppressive agents in general and stratified by sex n (%)

	Thiopurines	Thiopurines1,2	Methotrexate	Methotrexate1,2
Myelosuppression	33 (6)	12 (36)	NA	NA
Hepatotoxicity	33 (6)	19 (58)	10 (6)	6 (60)
Pancreatitis	10 (2)	2 (20)	NA	NA
Gastro-intestinal side-effects	23 (4)	8 (35)	10 (6)	6 (60)
Arthralgia and/or myalgia	11 (2)	5 (45)	2 (1)	1 (50)
Cutaneous side-effects	10 (2)	4 (40)	3 (2)	3 (100)
Infectious	6 (1)	3 (50)	2 (1)	1 (50)
Others3	23 (4)	7 (30)	13 (7)	2 (15)
Not specified4	6 (1)	3 (50)	4 (2)	1 (25)

¹No significant difference observed between males and females for none of the ADRs as tested with two-sided χ² test² Number and percentage of males in the group of patients with adverse drug reactions (ADR) to thiopurines;

³Number of all the people treated with the medicine;

⁴Headache, paresthesia, hair loss, fatigue, emotional instability, malaise; specific for methotrexate-injection site reaction. NA: Not available.

Table 3 Types of adverse drug reactions to respective anti-tumor necrosis factor agents in general and stratified by sex n (%)

	Infliximab1	Infliximab23	P value2	Adalimumab	Adalimumab23	P value2
Allergic reaction	33 (15)	7 (21)	0.045	7 (7)	0	0.039
Cutaneous SE	9 (4)	5 (56)	0.492	3 (3)	3 (100)	0.064
Neurological SE	4 (1.8)	0	0.146	2 (2)	0	0.512
Dyspnoea	4 (1.8)	0	0.146	1 (1)	0	1.00
Arthralgia and/or myalgia	11 (5)	4 (45)	1.00	3 (3)	1 (33)	1.00
Injection site reactions4	NA	NA		3 (3)	1 (33)	1.00
Infectious SE	0	0		3 (3)	1 (33)	1.00
Malignancy	16 (0.4)	16 (100)	0.41	0	0
Lupus-like	1 (0.4)	0		0	0
Others5	8 (3.5)	2 (25)	0.476	0	0

¹Number of all the people treated with the medicine;

²Two-sided χ² test to compare the differences in the frequencies of specific adverse drug reaction between males and females;

³Number of males;

⁴In case of adalimumab;

⁵Abdominal pain, hair loss, fatigue, malaise, emotional instability;

⁶Testis carcinoma. NA: Not available.