A short 2 week dose titration regimen reduces the severity of flu-like symptoms with initial interferon gamma-1b treatment

Figures & data

Table 1. Criteria for assessment of FLS.

	Score
Symptom	0	1	2	3	4
Muscle Aches	Absent	Mild: did not interfere with daily activities	Moderate: sufficient to interfere with daily activities	Severe: bed rest required	Very severe: medical attention required
Chills	Absent	Mild: did not interfere with daily activities	Moderate: sufficient to interfere with daily activities	Severe: bed rest required	Very severe: medical attention required
Tiredness	Absent	Mild: did not interfere with daily activities	Moderate: sufficient to interfere with daily activities	Severe: bed rest required	Very severe: medical attention required
Fever	<99.1°F	≥99.1°F to <100.1°F	≥100.1°F to <101.1°F	≥101.1°F to <102.1°F	≥102.1°F

FLS: flu-like symptoms. °F can be converted to °C by ((°F-32) X 0.556).

Table 2. Subject disposition by treatment sequence.

	Titration/ No Titration N = 20	No Titration/ Titration N = 20	Total N = 40
Randomized	20 (100.0)	20 (100.0)	40 (100.0)
ITT (safety)	20 (100.0)	20 (100.0)	40 (100.0)
Discontinued	5 (25.0)	10 (50.0)	15 (37.5)
Reason for discontinuation:
FLS, any	1 (5.0)	0	1 (2.5)
Headache, nausea, or vomiting	0	0	0
Injection site reaction	0	0	0
Other adverse event	0	3 (15.0)	3 (7.5)
Protocol violation	0	1 (5.0)	1 (2.5)
Withdrew consent	4 (20.0)	5 (25.0)	9 (22.5)
Lost to follow-up	0	1 (5.0)	1 (2.5)

Table 3. Discontinuation rates by treatment regimen and treatment period.

	Titration N = 32	No Titration N = 35	p Value
Period 1 – n	20	20
Discontinuation (%)	5 (25.0)	8 (40.0)	0.50
Period 2 – n	12	15
Discontinuation (%)	2 (16.7)	0

Table 4. Demographics and baseline characteristics by treatment sequence.

	Titration/ No Titration N = 20	No Titration/ Titration N = 20	Total N = 40
Age (yrs)
Mean (SD)	34.2 (12.09)	33.2 (10.06)	33.7 (10.99)
Median	30.5	30.0	30.0
Range	19, 54	18, 49	18, 54
Race
White	12 (60.0)	11 (55.0)	23 (57.5)
Black	8 (40.0)	8 (40.0)	16 (40.0)
Asian	0	1 (5.0)	1 (2.5)
Pacific Islander	0	0	0
Native American  or Alaskan	0	0	0
Ethnicity
Hispanic	0	0	0
Non-Hispanic	20 (100.0)	20 (100.0)	40 (100.0)
Sex
Female	11 (55.0)	11 (55.0)	22 (55.0)
Male	9 (45.0)	9 (45.0)	18 (45.0)
Height (cm)
Mean (SD)	172.36 (9.967)	170.89 (10.996)	171.63 (10.385)
Median	171.60	170.00	171.50
Range	152.9, 187.7	154.5, 200.9	152.9, 200.9
BMI (kg/m^2)
Mean (SD)	25.52 (3.406)	25.69 (3.301)	25.60 (3.312)
Median	24.95	24.50	24.75
Range	18.9, 31.4	21.6, 31.5	18.9, 31.5
BSA (m^2)
Mean (SD)	1.89 (0.195)	1.87 (0.195)	1.88 (0.193)
Median	1.90	1.90	1.90
Range	1.6, 2.2	1.6, 2.3	1.6, 2.3

BMI; body mass index; BSA: body surface area; SD: standard deviation.

Figure 1. Mean change in severity of FLS at 8 hours post-injection over 19 days, by treatment regimen.

Table 5. Change in severity of FLS scores at 8 hours post-injection over 3 weeks, by day.

Repeated Measures Model Effect			p Value
Sequence			0.66
Period			0.14
Regimen (Titration, No Titration)			0.02
Day			0.25
Titration x Day			0.11
Covariates
Drop-Out (yes/no)			0.48
Treatment Length			0.31
Least Squares Means (SE)	Titration	No Titration	p Value
Overall	0.21 (0.102)	0.34 (0.100)	0.02
Day 1	0.18 (0.142)	0.68 (0.138)	<0.01
Day 3	0.22 (0.142)	0.50 (0.138)	0.05
Day 5	0.18 (0.142)	0.36 (0.138)	0.23
Day 8	0.28 (0.142)	0.25 (0.138)	0.83
Day 10	0.28 (0.142)	0.22 (0.138)	0.68
Day 12	0.31 (0.142)	0.22 (0.138)	0.54
Day 15	0.15 (0.142)	0.22 (0.138)	0.66
Day 17	0.18 (0.142)	0.39 (0.138)	0.17
Day 19	0.12 (0.142)	0.19 (0.138)	0.65

Figure 2. Mean change in severity of fever at 8 hours post-injection over 19 days, by treatment regimen.

Table 6. Summary of adverse events by system organ class occurring >5% by treatment regimen.

System Organ Class/ Preferred Term	Titration N = 32 (n, %)	No Titration N = 35 (n, %)
General disorders and administration site conditions	28 (87.5)	29 (82.9)
Injection site erythema	16 (50.0)	20 (57.1)
Pyrexia	17 (53.1)	19 (54.3)
Fatigue	10 (31.3)	8 (22.9)
Influenza-like illness	7 (21.9)	8 (22.9)
Injection site pain	9 (28.1)	7 (20.0)
Injection site reactions	8 (25.0)	7 (20.0)
Chills	2 (6.3)	2 (5.7)
Injection site induration	1 (3.1)	2 (5.7)
Nervous system disorders	16 (50.0)	20 (57.1)
Headache	16 (50.0)	20 (57.1)
Dizziness	2 (6.3)	2 (5.7)
Gastrointestinal disorders	9 (28.1)	6 (17.1)
Nausea	6 (18.8)	6 (17.1)
Musculoskeletal and connective tissue disorders	8 (25.0)	5 (14.3)
Myalgia	8 (25.0)	5 (14.3)
Respiratory, thoracic and mediastinal disorders	5 (15.6)	1 (2.9)
Upper respiratory tract infection	3 (9.4)	0