Efficacy and effectiveness of the herbal medicinal product BNO 1016 in the management of acute rhinosinusitis in the context of antibiotic stewardship

Figures & data

Figure 1. Meta-analysis: MSS LS mean difference of BNO 1016 treatment vs. placebo in the full analysis data set (FAS). MSS LS mean difference at day 14 is depicted for the overall pooled population of ARhiSi-1 (placebo and 480 mg BNO 1016 treatment arm) and ARhiSi-2 as well as for the subgroups with moderate/severe (MSS ≥10) and none/mild symptoms at baseline. MSS LS mean difference from the ARhiSi-2 trial is shown as reference. MSS: Major Symptom Score.

Table 1. Meta-analysis: Mean MSS and mean SNOT-20 as well as least squares (LS) mean differences at day 14 between BNO 1016 and placebo, full analysis data set (FAS).

MSS (FAS)	BNO 1016 480 mg Mean (SD) MSS	Placebo Mean (SD) MSS	LS Mean Difference in MSS (95% CI)	p-value
Overall	2.5 (2.54)	3.5 (3.59)	−1.9 (−2.4, −1.4)	<0.0001
Subgroup moderate/severe	2.4 (2.29) −9.7 (2.24)	4.1 (3.83) −7.7 (4.37)	−2.3 (−3.1, −1.5) −2.3 (−3.1, −1.5)	<0.0001 <0.0001
Subgroup none/mild	2.5 (2.66) −6.8 (2.76)	3.2 (3.45) −6.3 (3.75)	−0.7 (−1.3, −0.1) −0.7 (−1.3, −0.1)	0.0160 0.0160
SNOT-20 (FAS)	BNO 1016 480 mg Mean (SD) SNOT-20	Placebo Mean (SD) SNOT-20	LS Mean Difference in SNOT-20 (95% CI)	p-value
Overall	12.3 (13.52)	15.8 (16.40)	−3.5 (−5.7, −1.4)	0.0010
Subgroup moderate/severe	12.3 (14.20)	18.7 (17.92)	−4.9 (−8.9, −0.9)	0.0158
Subgroup none/mild	12.3 (13.19)	14.5 (15.54)	−2.1 (−4.6, 0.4)	0.0932

SD, standard deviation; CI, confidence interval; MSS, Major Symptom Score.

Figure 2. Retrospective cohort study: Selection of study patients from the IMS® Disease Analyzer database.

Table 2. Retrospective cohort study: Baseline characteristics of the study patients.

Variable	Antibiotics	Nasal spray without CS	Topical INCS	BNO 1016	Antibiotics + nasal spray without CS
Prescriptions, N	94,756	19,236	18,716	10,087	19,199
Age, mean (SD) Age, median (25%–75%) Age, min.–max.	40.7 (17.5) 39 (27–53) 1–96	35.7 (20.1) 34 (21–50) 1–95	42.2 (18.0) 41 (28–55) 2–94	40.1 (16.5) 38 (27–52) 3–92	38.5 (18.9) 37 (24–52) 1–94
Age <18 yrs, %	7.0	19.7	7.4	4.5	14.1
Age ≥18 yrs, %	93.0	80.3	92.6	95.5	85.9
Male, %	40.3	41.2	38.8	41.1	42.7
CCI, mean (SD) CCI, median (25%–75%) CCI, min.–max.	0.06 (0.32) 0 (0–0) 0–3	0.03 (0.22) 0 (0–0) 0–3	0.03 (0.20) 0 (0–0) 0–3	0.05 (0.29) 0 (0–0) 0–3	0.03 (0.23) 0 (0–0) 0–3
Variable	Antibiotics +  INCS	Antibiotics +  analgesics	BNO 1016 +  nasal spray without CS	Nasal spray without CS +  analgesic	Antibiotics +  BNO 1016
Prescriptions, N	13,119	11,667	6,062	5,312	5,228
Age, mean (SD) Age, median (25%–75%) Age, min.–max.	41.3 (16.5) 40 (29–53) 3–94	38.4 (17.0) 37 (26–50) 1–93	40.5 (17.3) 38 (26–53) 4–95	32.5 (18.0) 31 (19–46) 1–93	41.8 (16.2) 40 (29–53) 10–92
Age <18 yrs, %	6.1	9.4	5.4	21.1	3.5
Age ≥18 yrs, %	93.9	90.6	94.6	78.9	96.5
Male, %	40.2	45.6	39.3	46.4	39.4
CCI, mean (SD) CCI, median (25%–75%) CCI, min.–max.	0.03 (0.22) 0 (0–0) 0–3	0.06 (0.30) 0 (0–0) 0–3	0.03 (0.22) 0 (0–0) 0–3	0.03 (0.23) 0 (0–0) 0–3	0.05 (0.32) 0 (0–0) 0–3

All patients are shown (n = 203,382), both reported from GPs as well as ENT specialists. Sorted by number of prescriptions, monotherapies are presented first.

CCI, Charlson Comorbidity Index; CS, corticosteroids; INCS, intranasal corticosteroids; SD, standard deviation.

Figure 3. Retrospective cohort study: Prescription of antibiotics due to ARS within 31–365 days after start of therapy. Multivariable Cox proportional hazard regression adjusted for sex, age, insurance status, month and CCI. AB: Antibiotics; CI: Confidence interval; CS: Corticosteroids; INCS: Intranasal corticosteroids.

Figure 4. Retrospective cohort study: Sick leave ≥7 days within first 30 days after therapy begin (a) and medical appointments due to ARS within 4–30 days after therapy begin (b). For (a) and (b): Multivariable logistic regression; All adjusted for sex, age, insurance status, month and CCI. CI: Confidence interval; CS: Corticosteroids; INCS: Intranasal corticosteroids.

Data availability statement

The data that support the findings of this study are available from the corresponding author, C Bachert, upon reasonable request.