Efficacy and Safety of Lefamulin vs Moxifloxacin for Treatment of Community-acquired Bacterial Pneumonia
Introduction
Lefamulin is a promising novel pleuromutilin antibiotic. It had demonstrated its potent activity against commonly encountered community-acquired bacterial pneumonia (CAPB) pathogens, even for antibiotic-resistant bacteria. Clinical studies evaluating the usefulness of lefamulin in the treatment of infectious disease is limited. Lefamulin Evaluation Against Pneumonia (LEAP) program comprised of 2 phase III randomized, multicenter, multinational studies LEAP 1 and LEAP 2.
Aim
To compare the efficacy and safety of lefamulin and moxifloxacin for treating CABP
Patient Profile
Patients with CABP infection enrolled in studies LEAP 1 and LEAP 2
Methods
- This is an integrated analysis of 2 phase III trials
- LEAP 1 compared the clinical efficacy and tolerability of Lefamulin (150mg intravenous [IV], every 12hours) and moxifloxacin (400mg IV every 24hours) in adult patients with CABP at pneumonia outcome research team (PORT) risk class ≥ III.
- LEAP 2 compared the effect and safety of oral lefamulin (600mg every 12hours for 5 days) and oral moxifloxacin (400mg every 24hours for 7 days) in adult patients with CABP at PORT risk class II, III or IV and
- Total of 1289 patients from these two trials was included in this analysis
- Lefamulin Group: n = 646
- Moxifloxacin Group: n = 643
Endpoints
- The proportion of patients with early clinical response (ECR) at early clinical assessment and clinical response at the end of treatment (EOT) and test of cure (TOC) (5–10 days after EOT)
- ECR responders were defined as improvement in ≥2 of 4 CABP signs/symptoms, had no worsening in any CABP sign/symptom, and had not received other non-study antibiotic for CABP at 96±24hours after first study drug dose
- A clinical responder was defined as successful if resolution or improvement of CABP signs/symptoms and no additional antibiotics was needed for CABP
Results
|
Characteristics |
No of patients (%) | |
|
Lefamulin (n =646) |
Moxifloxacin (n =643) | |
|
Mean age, yr |
58.9 |
58.7 |
|
Age <65 yr |
378 (58.5) |
394(61.3) |
|
Age 65–74 yr |
152 (23.5) |
145 (22.6) |
|
Age ≥ 75 yr |
116 (18.0) |
104 ∗16.2) |
|
Male sex |
377 (58.4) |
340 (52.9) |
|
Mean body mass index |
26.5 |
26.4 |
|
Race |
|
|
|
White race |
513 (79.4) |
509 (79.2) |
|
Asian |
72 (11.1) |
72 (11.2) |
|
American Indian or Alaskan native |
24 (3.7) |
17(2.6) |
|
Black |
30 (4.6) |
34 (5.3) |
|
Others |
7 (1.1) |
11 (1.7) |
|
Systemic inflammatory response syndrome |
621 (96.1) |
609 (94.7) |
|
PORT risk |
|
|
|
I |
1 (0.2) |
2 (0.3) |
|
II |
183 (28.3) |
190 (29.5) |
|
III |
341 (52.8) |
334 (51.9) |
|
IV |
116 (18.0) |
112 (17.4) |
|
V |
5 (0.8) |
5 (0.8) |
|
Bacteremia |
13 (2.0) |
12 (1.9) |
|
Met ATS minor severity criteria |
85 (13.2) |
85 (13.2) |
ATS = American Thoracic Society,
- Lefamulin was noninferior to moxifloxacin (RR: 0.99, 95% CI: 0.95–1.02, I2=0%)
- No significant difference was observed concerning clinical response at the test of cure between the lefamulin and moxifloxacin groups (for modified intention to treat population, RR: 0.98, I2=0%; for clinically evaluable population, RR: 0.96, I2=0%)
- Lefamulin and moxifloxacin demonstrated high rates of at early clinical assessment and clinical response rate at TOC across all baseline CABP pathogens (Table 2)
- Lefamulin exhibit similar clinical efficacy to moxifloxacin for most of CABP pathogens, except Moraxella catarrhalis
|
|
Early clinical response No. (%) |
Clinical response No. (%) | ||||
|
Lefamulin |
Moxifloxacin |
Risk ratio |
Lefamulin |
Moxifloxacin |
Risk ratio | |
|
Streptococcus pneumonia |
192/216 |
206/223 |
0.96 |
184/216 |
193/223 |
0.98 |
|
Staphylococcus aureus |
23/23 |
10/10 |
1.00 |
20/23 |
9/10 |
0.99 |
|
Haemophilus influenzae |
97/107 |
98/105 |
0.97 |
95/107 |
88/105 |
1.06 |
|
Moraxella catarrhalis |
41/46 |
22/22 |
0.92 |
37/46 |
22/22 |
0.83 |
|
Mycoplasma pneumoniae |
3639 |
32/34 |
0.99 |
35/39 |
33/34 |
0.94 |
|
Legionella pneumophila |
29/34 |
28/31 |
0.94 |
27/34 |
26/31 |
0.95 |
|
Chlamydophila pneumoniae |
25/27 |
30/31 |
0.95 |
20/27 |
23/31 |
0.96 |
- Lefamulin was associated with a similar risk of adverse events as moxifloxacin
- For the common gastrointestinal adverse event, the risk of nausea and diarrhoea was 4.2% and 7.3% among lefamulin group
- Both were higher than those of moxifloxacin (nausea, RR: 2.03, 95% CI: 1.02–4.03, I2=6%; diarrhoea, RR: 1.06, I2=96%).
Conclusion
Clinical efficacy and tolerability for lefamulin in the treatment of CABP were similar to those for moxifloxacin
Reference
Medicine.2020;99:29(e21223)
