Sample Selection and Characteristics
We initially identified 1,115 adult patients who had at least one visit with a primary diagnosis of psoriasis during the study period. Forty-two percent (n = 473) of those patients had at least three visits with a primary diagnosis of psoriasis and who were not missing all SF data for the first three observed visits. (Fig. 1) Of the 473 patients, 239 (51%) met the definition for MTE between their first and third observed visits (Visits 1 and 3).
The patients’ clinical and demographic characteristics at Visit 1 are shown in Table 1 for the entire cohort and separately for the two treatment groups. Patients were, on average, 46.9 years of age, and almost half (49.3%) were female. Common comorbid conditions included depression (14.4%), hyperlipidemia (10.8%), obesity (8.7%), and diabetes mellitus (8.5%). The majority of patients (86.5%) had plaque psoriasis; 7.4% had palmoplantar disease and 2.5% had nail disease. Itching was by far the most commonly reported symptom (72.7%) followed by pain (28.5%), cracking skin (27.9%), bleeding (23.5%), and sleep disturbances (16.1%). Approximately one-quarter of the entire cohort used topical corticosteroids, 28% used biologics, and 17% used conventional oral therapies at Visit 1; 15% of patients did not receive any treatment at Visit 1. Table 1 also shows the (unweighted) mean values of the psoriasis severity measures at Visit 1 for patients who did and did not receive MTE. Patients who received MTE had worse PtNRS (6.1 vs. 2.9), BSA (6.5 vs. 1.9), pPGA (2.3 vs. 1.3), and oPGA (2.4 vs. 1.3) at Visit 1 than patients who did not receive MTE. Patients who experienced MTE were more likely to have been female and to have had anxiety, hypertension, and cardiovascular disease and to have been obese than patients who did not undergo MTE. Patients who received MTE were more likely to have their psoriasis involve difficult-to-treat body sites, such as the groin (4.4 times), genitals (3.7 times), and gluteal cleft (2.5 times) at Visit 1 and had a larger number of body locations involved (4.0 vs. 1.9) than patients who did not undergo MTE. Patients who underwent MTE were also more likely to report psoriasis exacerbations with stress and dry climate, and were more likely to report presence of itch, pain, bleeding, cracking, and sleep disturbance than patients without MTE. Patients who experienced MTE were 3.3 times, 1.6 times, 2.4 times, and 3.2 times less likely to have used biologics, oral systems therapies, phototherapy, and multiple treatments, respectively, at Visit 1 than patients who did not experience MTE. Patients who did not undergo MTE were 3.8 and 8.0 times more likely to have used topical medications or no treatment at Visit 1 than patients who experienced MTE. The original (unweighted and unimputed) data and the unweighted and weighted imputed data for Visit 1 are summarized, stratified by MTE status, in Appendices A and B, respectively, of the Supplementary Materials.
Table 1
Patient Characteristics at Visit 1, by Treatment Escalation Group
Visit 1 Characteristic
|
All Patients
(N = 473)
|
No Meaningful Treatment Escalation (N = 234)
|
Meaningful Treatment Escalation (N = 239)
|
P-value*
|
Mean age, y (SD)
|
46.9 (15.1)
|
47.7 (15.3)
|
46.1 (14.9)
|
0.25
|
Female sex, N (%)
|
233 (49.3)
|
100 (42.7)
|
133 (55.6)
|
< 0.01
|
Comorbid conditions, N (%)
|
|
|
|
|
Depression
|
68 (14.4)
|
33 (14.1)
|
35 (14.6)
|
0.87
|
Hyperlipidemia
|
51 (10.8)
|
24 (10.3)
|
27 (11.3)
|
0.72
|
Obesity
|
41 (8.7)
|
13 (5.6)
|
28 (11.7)
|
0.02
|
Diabetes mellitus
|
40 (8.5)
|
18 (7.7)
|
22 (9.2)
|
0.55
|
Hypertension
|
37 (7.8)
|
8 (3.4)
|
29 (12.1)
|
< 0.01
|
Anxiety disorders
|
29 (6.1)
|
6 (2.6)
|
23 (9.6)
|
< 0.01
|
Cardiovascular disease
|
26 (5.5)
|
7 (3.0)
|
19 (7.9)
|
0.02
|
Skin cancer
|
8 (1.7)
|
2 (0.9)
|
6 (2.5)
|
0.29
|
Coindications for biologics, N (%)
|
|
|
|
|
Psoriatic arthritis
|
84 (17.8)
|
49 (20.9)
|
35 (14.6)
|
0.07
|
Rheumatoid arthritis
|
12 (2.5)
|
7 (3.0)
|
5 (2.1)
|
0.53
|
Psoriasis phenotype, N (%)
|
|
|
|
|
Plaque
|
409 (86.5)
|
206 (88.0)
|
203 (84.9)
|
0.32
|
Palmoplantar
|
35 (7.4)
|
11 (4.7)
|
24 (10.0)
|
0.03
|
Nail disease
|
12 (2.5)
|
6 (2.6)
|
6 (2.5)
|
0.97
|
Other phenotypes
|
15 (3.2)
|
4 (1.7)
|
11 (4.6)
|
0.11
|
Mean number of body location affected (SD)
|
3.0 (2.6)
|
1.9 (1.9)
|
4.0 (2.7)
|
< 0.01
|
Body locations affected, N (%)
|
|
|
|
|
Upper extremities, elbows, dorsal hands
|
242 (51.2)
|
94 (40.2)
|
148 (61.9)
|
< 0.01
|
Lower extremities
|
241 (51.0)
|
89 (38.0)
|
152 (63.6)
|
< 0.01
|
Scalp
|
198 (41.9)
|
64 (27.4)
|
134 (56.1)
|
< 0.01
|
Back
|
140 (29.6)
|
37 (15.8)
|
103 (43.1)
|
< 0.01
|
Abdomen
|
124 (26.2)
|
34 (14.5)
|
90 (37.7)
|
< 0.01
|
Ears
|
75 (15.9)
|
17 (7.3)
|
58 (24.3)
|
< 0.01
|
Knees
|
68 (14.4)
|
29 (12.4)
|
39 (16.3)
|
0.22
|
Face
|
66 (14.0)
|
16 (6.8)
|
50 (20.9)
|
< 0.01
|
Gluteal cleft
|
54 (11.4)
|
15 (6.4)
|
39 (16.3)
|
< 0.01
|
Palms
|
37 (7.8)
|
12 (5.1)
|
25 (10.5)
|
0.03
|
Soles
|
37 (7.8)
|
13 (5.6)
|
24 (10.0)
|
0.07
|
Feet
|
32 (6.8)
|
5 (2.1)
|
27 (11.3)
|
< 0.01
|
Neck
|
30 (6.3)
|
6 (2.6)
|
24 (10.0)
|
< 0.01
|
Genitals
|
29 (6.1)
|
6 (2.6)
|
23 (9.6)
|
< 0.01
|
Groin/Inguinal Fold
|
22 (4.7)
|
4 (1.7)
|
18 (7.5)
|
< 0.01
|
Axillae
|
10 (2.1)
|
2 (0.9)
|
8 (3.3)
|
0.11
|
Symptom triggers, N (%)
|
|
|
|
|
Stress
|
94 (19.9)
|
28 (12.0)
|
66 (27.6)
|
< 0.01
|
Dry climate
|
73 (15.4)
|
26 (11.1)
|
47 (19.7)
|
0.01
|
No triggers
|
67 (14.2)
|
31 (13.2)
|
36 (15.1)
|
0.57
|
Infection
|
33 (7.0)
|
10 (4.3)
|
23 (9.6)
|
0.02
|
Skin trauma
|
25 (5.3)
|
8 (3.4)
|
17 (7.1)
|
0.07
|
Others (sunlight, pregnancy, humidity)
|
11 (2.3)
|
5 (2.1)
|
6 (2.5)
|
0.79
|
Symptoms, %
|
|
|
|
|
Itching
|
344 (72.7)
|
142 (60.7)
|
202 (84.5)
|
< 0.01
|
Pain
|
135 (28.5)
|
35 (15.0)
|
100 (41.8)
|
< 0.01
|
Cracked skin
|
132 (27.9)
|
35 (15.0)
|
97 (40.6)
|
< 0.01
|
Bleeding
|
111 (23.5)
|
30 (12.8)
|
81 (33.9)
|
< 0.01
|
Sleep disturbances
|
76 (16.1)
|
12 (5.1)
|
64 (26.8)
|
< 0.01
|
Psoriasis severity measures (SD)**
|
|
|
|
|
Patient-reported numerical rating scale
|
4.5 (3.1)
|
3.0 (2.7)
|
6.1 (2.8)
|
< 0.01
|
Body surface area
|
4.2 (7.8)
|
1.9 (3.6)
|
6.4 (9.8)
|
< 0.01
|
Plaque PGA
|
1.8 (1.2)
|
1.3 (1.2)
|
2.3 (1.1)
|
< 0.01
|
Overall PGA
|
1.8 (1.3)
|
1.3 (1.1)
|
2.4 (1.2)
|
< 0.01
|
Treatment, %
|
|
|
|
< 0.01
|
Biologics
|
132 (27.9)
|
101 (43.2)
|
31 (13.0)
|
|
Topical medications
|
117 (24.7)
|
24 (10.3)
|
93 (38.9)
|
|
Oral systemics
|
82 (17.3)
|
50 (21.4)
|
32 (13.4)
|
|
No treatment
|
73 (15.4)
|
8 (3.4)
|
65 (27.2)
|
|
Multiple treatments
|
49 (10.4)
|
37 (15.8)
|
12 (5.0)
|
|
Phototherapy
|
20 (4.2)
|
14 (6.0)
|
6 (2.5)
|
|
Notes:*P-values for comparing patients who did and did not experience meaningful treatment escalation (P-values were calculated using the independent sample t-test for continuous measures and the chi-squared test for categorical measures). **Multiply imputed data. |
Abbreviations: N, number; PGA, physician global assessment; SD, standard deviation. |
Panel A of Table 2 displays the transition matrix of treatments used at Visits 1 and 3 for patients who did not experience MTE. Most patients were using the same type of treatment at Visit 3 as they were at Visit 1. For example, of 101 patients who used biologics at Visit 1, 90 (89.1%) were still using biologics, seven switched (6.9%) to using only topical medications, and four (4.0%) were not using any treatment at Visit 3. Of the 24 who used topical medications at Visit 1, most of them (17; 70.8%) continued to use topical medications at Visit 3. Panel B of Table 2 displays the transition matrix of treatments used at Visits 1 and 3 for patients who did experience MTE. Figure 2 displays the corresponding Sankey diagram, which is a graphical representation depicting the therapy transitions for patients who experienced MTE. Almost all patients who did not use any treatment or who only used topical medications at Visit 1 switched to a biologic or oral systemic therapy (83.5%). More than half (58.1%) of the patients who were using a biologic at Visit 1 were still using a biologic (albeit different ones) or were using oral systemic treatments at Visit 3; a similar pattern was observed for patients who used an oral systemic therapy at Visit 1. Half of the patients who were using multiple treatments at Visit 1 were exclusively using biologics at Visit 3.
Table 2. Transition Matrices for Treatment Changes Between Visits 1 and 3
A. Patients Who Did Not Undergo Meaningful Treatment Escalations (N=234)
Visit 1 Treatments
|
Visit 3 Treatments
|
Biologics (N=99)
|
Oral Systemic (N=42)
|
Topical Medications (N=40)
|
No treatment (N=22)
|
Multiple Treatments (N=18)
|
Phototherapy (N=13)
|
Biologics (N=101), N (%)
|
90 (89.1)
|
0 (0.0)
|
7 (6.9)
|
4 (4.0)
|
0 (0.0)
|
0 (0.0)
|
Oral Systemics (N=50) , N (%)
|
0 ( 0.0)
|
36 (72.0)
|
8 (16.0)
|
6 (12.0)
|
0 (0.0)
|
0 (0.0)
|
Multiple Treatments (N=37) , N (%)
|
9 (24.3)
|
6 (16.2)
|
0 (0.0)
|
2 (5.4)
|
18 (48.6)
|
2 (5.4)
|
Topical medications (N=24) , N (%)
|
0 (0.0)
|
0 (0.0)
|
17 (70.8)
|
7 (29.2)
|
0 (0.0)
|
0 (0.0)
|
Phototherapy (N=14) , N (%)
|
0 (0.0)
|
0 (0.0)
|
2 (14.3)
|
1 (7.1)
|
0 (0.0)
|
11 (78.6)
|
No treatment (N=8) , N (%)
|
0 (0.0)
|
0 (0.0)
|
6 (75.0)
|
2 (25.0)
|
0 (0.0)
|
0 (0.0)
|
B. Patients Who Underwent Meaningful Treatment Escalations (N=239)
Visit 1 Treatments
|
Visit 3 Treatments
|
Biologic (N=93)
|
Oral Systemics (N=88)
|
Multiple Treatments (N=45)
|
Phototherapy (N=13)
|
Topical Medications (N=0)
|
No treatment (N=0)
|
Topical Medications (N=93)
|
35 (37.6)
|
39 (41.9)
|
11 (11.8)
|
8 (8.6)
|
0 (0.0)
|
0 (0.0)
|
No treatment (N=65)
|
22 (33.8)
|
36 (55.4)
|
3 (4.6)
|
4 (6.2)
|
0 (0.0)
|
0 (0.0)
|
Oral Systemics (N=32)
|
15 (46.9)
|
8 (25.0)
|
8 (25.0)
|
1 (3.1)
|
0 (0.0)
|
0 (0.0)
|
Biologics (N=31)
|
15 (48.4)
|
3 (9.7)
|
13 (41.9)
|
0 (0.0)
|
0 (0.0)
|
0 (0.0)
|
Multiple Treatments (N=12)
|
6 (50.0)
|
1 (8.3)
|
5 (41.7)
|
0 (0.0)
|
0 (0.0)
|
0 (0.0)
|
Phototherapy (N=6)
|
0 (0.0)
|
1 (16.7)
|
5 (83.3)
|
0 (0.0)
|
0 (0.0)
|
0 (0.0)
|
Note: The percentages of patients using treatments at Visit 3 conditional on having using a treatment in Visit 1 were computed on a row-by-row basis.
Abbreviation: N, number.
Although several factors were more common among patients who experienced MTE than those who did not, as shown in Table 1 (cardiovascular disease, anxiety, obesity, and hypertension; almost all body locations affected; palmoplantar psoriasis; all symptoms; infection, stress, and dry climate as triggers; topical medications, no treatment), fewer factors were correlated with MTE based on the multivariable logistic regression model whose results are shown in Table 3. Patients with anxiety, hypertension, palmoplantar psoriasis, and psoriasis affecting their lower extremities at Visit 1 were more likely to have experienced MTE while patients with depression and those using biologic or oral systemic therapy, phototherapy, or multiple treatments (all vs. no treatment) were less likely to have experienced MTE.
Table 3
Unweighted Multiple Logistic Regression Model for Treatment Escalation
Visit 1 Characteristic
|
Odds Ratio
|
95% Confidence Interval
|
P-value
|
Age
|
1.00
|
0.98–1.02
|
0.98
|
Female sex
|
1.50
|
0.85–2.66
|
0.16
|
Comorbid conditions
|
|
|
|
Cardiovascular disease
|
0.97
|
0.21–4.45
|
0.97
|
Skin cancer
|
3.39
|
0.49–23.39
|
0.22
|
Anxiety disorders
|
10.14
|
1.98–51.93
|
< 0.01
|
Depression
|
0.23
|
0.08–0.65
|
< 0.01
|
Obesity
|
1.87
|
0.61–5.75
|
0.27
|
Diabetes
|
0.76
|
0.27–2.16
|
0.61
|
Hyperlipidemia
|
1.50
|
0.59–3.82
|
0.40
|
Hypertension
|
3.03
|
0.92–10.05
|
0.07
|
Coindications for biologics
|
|
|
|
Psoriatic arthritis
|
1.37
|
0.67–2.80
|
0.39
|
Rheumatoid arthritis
|
0.57
|
0.10–3.22
|
0.52
|
Psoriasis phenotype
|
|
|
|
Plaque phenotype
|
1.32
|
0.42–4.17
|
0.63
|
Nail disease phenotype
|
1.53
|
0.26–8.96
|
0.69
|
Palmoplantar phenotype
|
8.25
|
1.12–60.59
|
0.04
|
Other phenotypes
|
2.95
|
0.39–22.01
|
0.29
|
Body locations affected
|
|
|
|
Scalp
|
1.56
|
0.82–2.95
|
0.18
|
Back
|
2.15
|
1.03–4.48
|
0.04
|
Abdomen
|
1.00
|
0.45–2.20
|
1.00
|
Lower extremities
|
1.93
|
1.04–3.58
|
0.04
|
Upper extremities, elbows, dorsal hands
|
1.17
|
0.64–2.15
|
0.61
|
Face
|
1.76
|
0.70–4.43
|
0.23
|
Ears
|
1.79
|
0.74–4.37
|
0.20
|
Neck
|
0.50
|
0.11–2.22
|
0.36
|
Knees
|
0.57
|
0.25–1.30
|
0.18
|
Feet
|
1.65
|
0.44–6.13
|
0.46
|
Palms
|
1.56
|
0.50–4.82
|
0.44
|
Soles
|
0.39
|
0.06–2.41
|
0.31
|
Axillae
|
7.54
|
0.77–74.16
|
0.08
|
Gluteal cleft
|
0.33
|
0.11–0.96
|
0.04
|
Genitals, groin/inguinal fold
|
1.00
|
0.29–3.45
|
1.00
|
Symptom triggers
|
|
|
|
Infection
|
0.63
|
0.17–2.38
|
0.49
|
Trauma
|
1.76
|
0.49–6.29
|
0.38
|
Stress
|
1.42
|
0.69–2.91
|
0.34
|
Dry climate
|
0.94
|
0.43–2.07
|
0.88
|
No triggers
|
1.06
|
0.49–2.33
|
0.88
|
Other (sunlight, pregnancy, humidity)
|
0.86
|
0.16–4.74
|
0.86
|
Symptoms
|
|
|
|
Itching
|
1.31
|
0.67–2.55
|
0.43
|
Pain
|
1.30
|
0.63–2.70
|
0.48
|
Bleeding
|
1.17
|
0.54–2.55
|
0.69
|
Cracked skin
|
1.43
|
0.66–3.08
|
0.36
|
Sleep disturbances
|
2.10
|
0.84–5.30
|
0.11
|
Treatment (vs. no treatment)
|
|
|
|
Topical medications
|
0.43
|
0.16–1.16
|
0.09
|
Biologics
|
0.05
|
0.02–0.15
|
< 0.01
|
Oral systemics
|
0.07
|
0.02–0.20
|
< 0.01
|
Phototherapy
|
0.05
|
0.01–0.22
|
< 0.01
|
Multiple treatments
|
0.05
|
0.01–0.16
|
< 0.01
|
Note: *P-values for differences between Visits 1 and 3.
Abbreviations: N, number; NRS, numerical rating scale; PGA, physician global assessment; SD, standard deviation.