Cardiovascular Risk Associated with Methotrexate versus Retinoids in Patients with Psoriasis: A Nationwide Taiwanese Cohort Study

Figures & data

Figure 1 Study flow chart.

Table 1 Baseline Characteristics of Patients with Psoriasis Who Were Receiving Methotrexate or Retinoids Before and After Propensity Score Weighting

Characteristic	MTX Users (N = 13,777)	Retinoid Users (N = 6020)	MTX Weighted	Retinoid Weighted	Standardized Mean Difference Before IPTW	Standardized Mean Difference After IPTW
Age, years (mean ± SD), (median)	46.77 ± 15.28 (46)	48.59 ± 16.29 (48)	47.45 ± 15.42 (47)	47.2 ± 16.12 (46)	−0.12	0.02
Male (%)	64.96	72.87	67.52	68.39	−0.17	−0.02
Duration of Psoriasis (%)
0–1 months	23.92	30.1	25.75	25.05	−0.14	0.02
1–12 months	20.46	23.14	21.31	21.32	−0.06	0.00
1–4 years	27.19	26.31	27.01	27.1	0.02	0.00
>4 years	28.42	20.45	25.98	26.12	0.19	0.00
Psoriatic arthritis (%)	14.95	4.15	11.65	10.93	0.37	0.02
No. of outpatient visits (mean ± SD)	0.19 ± 0.63	0.22 ± 0.66	0.2 ± 0.66	0.2 ± 0.62	−0.05	0.00
No. of admissions (mean ± SD)	23.86 ± 20.92	23.85 ± 21.15	23.98 ± 21.42	23.95 ± 20.28	0.00	0.00
Charlson Comorbidity Score (%)
0	57.42	60.86	58.47	58.39	−0.07	0.00
1–4	40.88	37.44	39.8	39.26	0.07	0.01
≥5	1.7	1.69	1.77	1.94	0.00	−0.01
Concomitant Drugs (%)
Corticosteroid	44.2	40.43	43.04	42.21	0.08	0.02
Platelet inhibitors	11.03	12.57	11.56	11.67	−0.05	0.00
Beta-blockers	15.94	15.12	15.72	15.87	0.02	0.00
Angiotensin-converting enzyme inhibitors/ angiotensin II receptor blockers	14.34	14.92	14.59	15.2	−0.02	−0.02
Calcium antagonists	17.01	17.91	17.32	17.6	−0.02	−0.01
Loop diuretics	6.48	6.94	6.71	6.98	−0.02	−0.01
Thiazide diuretics	3.24	3.47	3.33	3.49	−0.01	−0.01
Spironolactone	1.51	1.63	1.56	1.64	−0.01	−0.01
Cholesterol-lowering drugs	9.57	7.89	9.11	9.45	0.06	−0.01
Glucose-lowering drugs	10.52	10.98	10.73	11.24	−0.01	−0.02
Selective cyclooxygenase 2 inhibitors	72.87	63.47	70.03	69.25	0.20	0.02
Anti-depressants	8.78	9.24	8.98	8.96	−0.02	0.00
Anti-hypertensive agents	4.05	4.8	4.3	4.38	−0.04	0.00
Vitamin K antagonists	0.4	0.37	0.39	0.36	0.00	0.00
Non-aspirin antiplatelet agents	4.67	5.07	4.82	4.86	−0.02	0.00
Low-dose aspirin	8.1	9.37	8.54	8.66	−0.04	0.00
Folic acid	1.83	0.96	1.56	1.28	0.07	0.02
Comorbidity (%)
Hypertension	24.05	25.2	24.46	24.95	−0.03	−0.01
Diabetes	12.83	13.24	13.02	13.46	−0.01	−0.01
Dyslipidemia	14.65	13.07	14.18	14.52	0.05	−0.01
Renal disease	3.11	3.49	3.29	3.53	−0.02	−0.01
Chronic obstructive pulmonary disease	8.76	9.42	9.01	9.06	−0.02	0.00
Liver disease	12.09	13.49	12.59	13.02	−0.04	−0.01
Median cumulative dose, mg (IQR)^a	105 (30–330)	1200 (560–2790)	-	-	-	-

Note:^aIn the as-treated analyses.

Abbreviations: SD, standard deviation; MTX, methotrexate; IPTW, inverse probability-of-treatment weighting; IQR, interquartile range.

Table 2 Numbers of Events, Person-Days, and Crude Incidence Rates Among Patients with Psoriasis Who Were Receiving Methotrexate or Retinoids

	MTX Users (N = 13,777)	Retinoid Users (N = 6020)
Intention-to-Treat
Composite Cardiovascular Outcome^a
Follow-up duration (person-years)	55,323	31,926
Number of events	1108	826
Crude incidence per 100,000 person-years	2003	2587
Ischaemic Heart Disease
Follow-up duration (person-years)	55,713	32,098
Number of events	404	278
Crude incidence per 100,000 person-years	725	866
Ischaemic Stroke
Follow-up duration (person-years)	55,416	31,984
Number of events	469	277
Crude incidence per 100,000 person-years	846	866
All-cause mortality
Follow-up duration (person-years)	56,727	32,870
Number of events	711	612
Crude incidence per 100,000 person-years	1253	1862
As-Treated
Composite Cardiovascular Outcome^a
Follow-up duration (person-years)	12,133	4648
Number of events	235	124
Crude incidence per 100,000 person-years	1937	2668
Ischaemic Heart Disease
Follow-up duration (person-years)	12,165	4645
Number of events	83	52
Crude incidence per 100,000 person-years	682	1119
Ischaemic Stroke
Follow-up duration (person-years)	12,137	4650
Number of events	109	45
Crude incidence per 100,000 person-years	898	968
All-Cause Mortality
Follow-up duration (person-years)	12,206	4665
Number of events	125	76
Crude incidence per 100,000 person-years	1024	1629

Notes:^aComposite cardiovascular outcome includes hospitalisations for ischaemic heart disease, ischaemic stroke, and/or all-cause mortality.

Abbreviation: MTX, methotrexate.

Figure 2 The inverse probability-weighted event-free survival curves for cardiovascular outcome-free survival among methotrexate or retinoid users. (A) Intention-to-treat analysis and (B) as-treated analysis.

Abbreviation: MTX, methotrexate.

Table 3 Hazard Ratios of Cardiovascular Outcomes Comparing Methotrexate (n=13,777) with Retinoids (n=6020) Use in Psoriasis Patients Weighted by Propensity Score

Methods	Crude HR	Adjusted HR^a
	HR (95% CI)	HR (95% CI)
Intention-to-Treat
Composite cardiovascular outcome ^b	0.78 (0.71–0.85)	0.84 (0.76–0.94)
Ischaemic heart disease	0.83 (0.71–0.97)	0.87 (0.71–1.06)
Ischaemic stroke	0.95 (0.82–1.11)	1.06 (0.89–1.27)
All-cause mortality	0.69 (0.62–0.77)	0.75 (0.66–0.85)
As-Treated
Composite cardiovascular outcome ^b	0.76 (0.61–0.94)	0.80 (0.62–1.04)
Ischaemic heart disease	0.61 (0.43–0.87)	0.57 (0.38–0.87)
Ischaemic stroke	0.96 (0.68–1.37)	0.93 (0.61–1.42)
All-cause mortality	0.65 (0.49–0.86)	0.73 (0.52–1.02)

Notes:^aAdjusted hazard ratios were based on propensity score weighting. ^bCardiovascular outcome includes hospitalisations for ischaemic heart disease, ischaemic stroke, and/or all-cause mortality.

Abbreviations: HR, hazard ratio; CI, confidence interval.

Figure 3 Adjusted hazard ratios for cardiovascular outcomes among methotrexate and retinoid users according to different subgroups using an intention-to-treat approach with weighted propensity score.

Abbreviations: HR, hazard ratios; CI, confidence interval.