Table 1.
Characteristics of cases receiving LTG who experienced SJS/TEN; reference group A: cases receiving LTG who experienced non-cutaneous ADRs; and reference group B: cases experiencing SJS/TEN after other drugs
| LTG with SJS/TEN | LTG without cutaneous ADRs*, Ref A |
SJS/TEN with other drugs, Ref B |
|||||||
| Total number of reports | 486 | 2609 | 4349 | ||||||
| Report features | Report variable | No. rep | % | No. rep | % | log OR (logOR 005. logOR 995)† | No. rep | % | log OR (logOR 005. logOR 995)† |
| Sex‡ | Male | 205 | 42.5 | 1248 | 49.8 | −0.42 (–0.68,–0.17) | 2329 | 54.7 | −0.69 (–0.96,–0.44) |
| Female | 277 | 57.5 | 1256 | 50.2 | 0.42 (0.19,0.63) | 1932 | 45.3 | 0.69 (0.46,0.90) | |
| Unspecified | 4 | 0.8 | 105 | 4.0 | −1.49 (–3.01,–0.44) | 88 | 2.0 | −0.73 (–2.25,0.31) | |
| Age groups | 0–27 days | 0 | 0.0 | 260** | 10.0 | −3.56 (–5.77,–2.22)§ | 12 | 0.3 | −0.34 (–2.56,0.99) |
| 28 days to 23 months | 3 | 0.6 | 167 | 6.4 | −2.25 (–3.89,–1.15)§ | 406 | 9.3 | −2.77 (–4.41,–1.68)§ | |
| 2 to 11 years | 228 | 46.9 | 1068 | 40.9 | 0.34 (0.09,0.58) | 2456 | 56.5 | −0.54 (–0.80,–0.31) | |
| 12 to 17 years | 255 | 52.5 | 1114 | 42.7 | 0.55 (0.31,0.78) | 1475 | 33.9 | 1.07 (0.83,1.30) § | |
| Report origin by geographical region | North America | 244 | 50.2 | 1266 | 48.5 | 0.10 (–0.15,0.32) | 1147 | 26.4 | 1.44 (1.20,1.67) § |
| Europe | 158 | 32.5 | 1015 | 38.9 | −0.39 (–0.70,–0.11) | 1354 | 31.1 | 0.09 (-0.22,0.37) | |
| Asia | 45 | 9.3 | 162 | 6.2 | 0.55 (–0.02,1.04) | 1382 | 31.8 | −2.07 (–2.64,–1.59)§ | |
| Latin America | 18 | 3.7 | 34 | 1.3 | 1.04 (0.16,1.74) | 85 | 2.0 | 0.68 (–0.19,1.38) | |
| Oceania | 13 | 2.7 | 103 | 3.9 | −0.44 (–1.45,0.33) | 137 | 3.2 | −0.18 (–1.19,0.60) | |
| Africa | 8 | 1.6 | 29 | 1.1 | 0.33 (–0.89,1.22) | 244 | 5.6 | −1.36 (–2.58,–0.47) | |
| Fatal outcome | Yes | 15 | 3.1 | 107 | 4.1 | −0.33 (–1.28,0.41) | 178 | 4.1 | −0.33 (–1.28,0.41) |
| Top co-reported drugs¶ with LTG in the primary dataset | Valproic acid | 207 | 42.6 | 493 | 18.9 | 1.60 (1.33,1.84) § | 181 | 4.2 | 3.63 (3.37,3.88) § |
| Clobazam | 21 | 4.3 | 115 | 4.4 | −0.02 (–0.84,0.63) | 36 | 0.8 | 1.55 (0.73,2.21)§ | |
| Clonazepam | 18 | 3.7 | 128 | 4.9 | −0.34 (–1.22,0.35) | 29 | 0.7 | 1.50 (0.62,2.19) § | |
| Amoxicillin | 16 | 3.3 | 8 | 0.3 | 1.70 (0.78,2.43)§ | 347 | 8.0 | −1.12 (–2.05,–0.40) | |
| Levetiracetam | 16 | 3.3 | 151 | 5.8 | −0.69 (–1.61,0.03) | 19 | 0.4 | 1.57 (0.65,2.30) § | |
| Quetiapine | 16 | 3.3 | 60 | 2.3 | 0.39 (–0.54,1.11) | 6 | 0.1 | 1.89 (0.97,2.62) § | |
| Top five reported ADRs¶ in the primary dataset MedDRA | SJS | 420 | 86.4 | 0 | 0.0 | – | 3538 | 81.4 | 0.54 (0.35,0.71) |
| TEN | 101 | 20.8 | 0 | 0.0 | – | 949 | 21.8 | −0.09 (–0.47,0.26) | |
| Rash | 68 | 14.0 | 0 | 0.0 | – | 180 | 4.1 | 1.66 (1.20,2.07)§ | |
| Fever | 59 | 12.1 | 56 | 2.1 | 2.16 (1.66,2.59)§ | 277 | 6.4 | 0.91 (0.41,1.34) | |
| Blister | 33 | 6.8 | 0 | 0.0 | – | 60 | 1.4 | 1.74 (1.08,2.30)§ | |
*Reports with cutaneous ADRs were excluded and defined with the MedDRA system organ class ‘Skin and subcutaneous tissue disorders’.
†The relative frequencies of report features for LTG and SJS/TEN were contrasted to the reference groups A and B, using ORs with adaptive statistical shrinkage. LogOR005 is the lower limit of the 99% CI, while logOR995 is the upper limit.
‡The denominator for the calculated percentage is based on numbers with a known value.
§Significant features were defined as those with logOR005>0.5 (feature in the primary dataset is reported significantly more frequently than in the reference group) or logOR995<−0.5 (feature in the primary dataset is reported less frequently than in the reference group). In this study, key features were defined as those features in the primary dataset that were significantly different from both reference groups A and B, with the exception of co-reported cutaneous reactions where comparison was only relevant to reference group B (since cutaneous reactions had been excluded in reference group A).
¶One unique report can be represented within more than one MedDRA preferred term or within more than one drug because one report can be recorded with more than one adverse reaction or drug.
**Many of the reports in the youngest age group concern in utero exposure and congenital anomalies.
ADR, adverse drug reaction; LTG, lamotrigine; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis