Table 4. Treatment reactions and adverse events possibly related to the treatment.
| Event | PDT-hemoporfin, 735 PT of 434 patients | PDT-placebo, 110 PT of 110 patients | P value | |||||
|---|---|---|---|---|---|---|---|---|
| n | Event rate† | Days to resolve‡ | n | Event rate† | Days to resolve‡ | |||
| Treatment reactions | ||||||||
| Pain | 713 | 97.0 (95.5 to 98.0) | 0–19 | 7 | 6.4 (3.1 to 12.6) | 0–2 | <0.0001 | |
| Burning sensation | 589 | 80.1 (77.1 to 82.9) | 0–10 | 32 | 29.1 (21.4 to 38.2) | 0–4 | <0.0001 | |
| Pruritus | 388 | 52.8 (49.2 to 56.4) | 0–47 | 12 | 10.9 (6.4 to 18.1) | 0–9 | <0.0001 | |
| Numbness | 1 | 0.1 (0.0 to 0.8) | 0 | 0 | 0.0 (0.0 to 3.4) | - | >0.999 | |
| Edema | 698 | 95.0 (93.1 to 96.3) | 0–21 | 4 | 3.6 (1.4 to 9.0) | 0–4 | <0.0001 | |
| Crusting | 496 | 67.5 (64.0 to 70.8) | 0–46 | 0 | 0.0 (0.0 to 3.4) | - | <0.0001 | |
| Purpura | 70 | 9.5 (7.6 to 11.9) | 2–15 | 0 | 0.0 (0.0 to 3.4) | - | 0.0007 | |
| Blistering | 51 | 6.9 (5.3 to 9.0) | 1–24 | 1 | 0.9 (0.2 to 5.0) | 3 | 0.0139 | |
| Adverse events | ||||||||
| Total adverse events | 241 | 32.8 (29.5 to 36.3) | - | 8 | 7.3 (3.7 to 13.7) | - | <0.001 | |
| Light-exposure related reactions | 10 | 1.4 (0.7 to 2.5) | - | 2 | 1.8 (0.5 to 6.4) | - | 0.955 | |
| Dyspnea, rash and photophobia | 1 | 0.1 (0.0 to 0.8) | 0 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Urticaria | 1 | 0.1 (0.0 to 0.8) | 0 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Photosensitive cheilitis | 1 | 0.1 (0.0 to 0.8) | 8 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Photosensitive dermatitis | 0 | 0.0 (0.0 to 0.5) | - | 1 | 0.9 (0.2 to 5.0) | 9 | - | |
| Dizziness and photophobia | 5 | 0.7 (0.3 to 1.6) | 0–21 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Photophobia | 2 | 0.3 (0.1 to 1.0) | 4–18 | 1 | 0.9 (0.2 to 5.0) | 5 | - | |
| Local adverse events | ||||||||
| Hyperpigmentation | 168 | 22.9 (20.0 to 26.0) | 16–379a | 0 | 0.0 (0.0 to 3.4) | - | <0.001 | |
| Hypopigmentation | 14 | 1.9 (1.1 to 3.2) | 27–268b | 0 | 0.0 (0.0 to 3.4) | - | 0.288 | |
| Temporary skin lesions | 8 | 1.1 (0.6 to 2.1) | 0 | 0.0 (0.0 to 3.4) | - | 0.566 | ||
| Rash maculo-papular | 3 | 0.4 (0.1 to 1.2) | 0–3 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Exudation | 1 | 0.1 (0.0 to 0.8) | 2 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Eczema | 1 | 0.1 (0.0 to 0.8) | 14 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Scaling | 1 | 0.1 (0.0 to 0.8) | 9 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Erythema | 1 | 0.1 (0.0 to 0.8) | 10 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Textural change | 1 | 0.1 (0.0 to 0.8) | 105 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Wound infection | 8 | 1.1 (0.6 to 2.1) | 2–12c | 0 | 0.0 (0.0 to 3.4) | - | 0.566 | |
| Atrophic scar | 4 | 0.5 (0.2 to 1.4) | 48–208d | 0 | 0.0 (0.0 to 3.4) | - | >0.999 | |
| Systemic adverse events | ||||||||
| Liver and biliary system disorders e | 8 | 1.1 (0.6 to 2.1) | 2 | 1.8 (0.5 to 6.4) | 0.854 | |||
| ALT, AST and TBil increase | 1 | 0.1 (0.0 to 0.8) | 52 | 1 | 0.9 (0.2 to 5.0) | - | ||
| ALT and AST increase | 3 | 0.4 (0.1 to 1.2) | 28–119 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| ALT increase | 1 | 0.1 (0.0 to 0.8) | 3 | 1 | 0.9 (0.2 to 5.0) | - | ||
| AST increase | 2 | 0.3 (0.1 to 1.0) | 6–7 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| TBil increase | 1 | 0.1 (0.0 to 0.8) | 54 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Gastro-intestinal system disorders | 6 | 0.8 (0.4 to 1.8) | 0–1 | 0 | 0.0 (0.0 to 3.4) | - | >0.999 | |
| Nausea | 5 | 0.7 (0.3 to 1.6) | 0–1 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Vomiting | 1 | 0.1 (0.0 to 0.8) | 0 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Cardiac disorders | 4 | 0.5 (0.2 to 1.4) | 47–154 | 1 | 0.9 (0.2 to 5.0) | 51 | 0.504 | |
| Ventricular arrhythmia | 1 | 0.1 (0.0 to 0.8) | 154 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Conduction disorder | 1 | 0.1 (0.0 to 0.8) | 47 | 1 | 0.9 (0.2 to 5.0) | 51 | - | |
| Non-specific ECG abnormal | 2 | 0.3 (0.1 to 1.0) | 47–50 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Respiratory system disorders | 3 | 0.4 (0.1 to 1.2) | 0–2 | 0 | 0.0 (0.0 to 3.4) | - | >0.999 | |
| Dyspnea | 3 | 0.4 (0.1 to 1.2) | 0–2 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| General symptoms | 3 | 0.4 (0.1 to 1.2) | 2–36 | 0 | 0.0 (0.0 to 3.4) | - | >0.999 | |
| Asthenia | 2 | 0.3 (0.1 to 1.0) | 2–30 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Sweating increased | 1 | 0.1 (0.0 to 0.8) | 36 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Eye abnormality | 2 | 0.3 (0.1 to 1.0) | 4–16 | 0 | 0.0 (0.0 to 3.4) | - | >0.999 | |
| Conjunctivitis | 1 | 0.1 (0.0 to 0.8) | 16 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Xerophthalmia | 1 | 0.1 (0.0 to 0.8) | 4 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| White cell and RES disorders | 1 | 0.1 (0.0 to 0.8) | 2 | 0 | 0.0 (0.0 to 3.4) | - | >0.999 | |
| Leukocytosis | 1 | 0.1 (0.0 to 0.8) | 2 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Nervous system disorders | 1 | 0.1 (0.0 to 0.8) | 7 | 1 | 0.9 (0.2 to 5.0) | 2 | 0.244 | |
| Dizziness | 0 | 0.0 (0.0 to 0.5) | - | 1 | 0.9 (0.2 to 5.0) | 2 | - | |
| Vertigo | 1 | 0.1 (0.0 to 0.8) | 7 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Tooth disorder | 1 | 0.1 (0.0 to 0.8) | 0 | 0 | 0.0 (0.0 to 3.4) | - | >0.999 | |
| Tooth infection | 1 | 0.1 (0.0 to 0.8) | 0 | 0 | 0.0 (0.0 to 3.4) | - | - | |
| Urinary system disorders | 0 | 0.0 (0.0 to 0.5) | - | 2 | 1.8 (0.5 to 6.4) | 52–54 | 0.017 | |
| Hematuria | 0 | 0.0 (0.0 to 0.5) | - | 1 | 0.9 (0.2 to 5.0) | 54 | - | |
| Proteinuria | 0 | 0.0 (0.0 to 0.5) | - | 1 | 0.9 (0.2 to 5.0) | 52 | - | |
Abbreviations: PT, patient-treatments; AST, aspartate transaminase; ALT, alanine aminotransferase; TBil, total bilirubin; ECG, electrocardiogram; RES, reticuloendothelial system.
Denotations
† Exposure adjusted event rate per 100 patient-treatments, Mean (95% CI)
‡ range, where 0 indicates resolution in less than one day
a Nine patients lost to follow-up
b Two patients lost to follow-up
c Healed with application of topical antibiotics
d One patient lost to follow-up
e An increase was defined as ALT or AST exceeding the upper limit of normal (ULN), or TBil exceeding 1.5ULN; All statistical comparisons were conducted using chi-square or Fisher’s exact test.