Table 1.
Patient’s characteristics at baseline and clinical course
| Case number | 1 | 2 | 3 | 4 | 5 | 6 |
| Age/Sex | 71/F | 44/M | 58/M | 47/M | 47/F | 66/F |
| Observation period | 48 days | 16 months | 43 days | 19 months | 12 months | 8 months |
| Clinical involvement at baseline* | ||||||
| Skin | + | + | + | + | + | + |
| Muscle | + | + | – | – | + | – |
| Joint | – | – | – | + | + | – |
| Lung (RP-ILD) | + | + | + | + | + | + |
| Laboratory data (baseline*/at the time of TOF dose-escalation/Last observation) | ||||||
| LDH (124–222 (U/L)) | 393/288/777 | 481/293/265 | 622/338/571 | 338/320/195 | 269/342/199 | 309/486/270 |
| CRP (0.00–0.14 (mg/dL)) | 0.19/5.32/4.03 | 2.09/0.03/0.02 | 6.05/3.91/3.28 | 0.64/0.05/0.01 | 1.61/0.01/0.01 | 0.75/0.32/0.01 |
| Lymphocyte (825–3870 (/μL)) | 186/134/105 | 680/529/1348 | 427/312/109 | 1145/117/570 | 266/93/231 | 1165/243/1411 |
| KL-6 (<500 (U/mL)) | 802/344/1370 | 416/564/526 | 1360/573/3242 | 685/762/399 | 434/1218/486 | 1045/1337/923 |
| Ferritin (12.0–60.0 (ng/dL)) | 1289/493/622 | 960/2959/134 | 1185/1592/1643 | 852/295/20 | 67/275/67 | 791/943/55 |
| MDA5 Ab (<32 (Index))† | 2050/300/70 | 2200/2200/31 | 3700/950/300 | 6650/900/5 | 3650/2700/21 | 3150/1350/30 |
| P/F ratio (mm Hg) | 350/220/64 | NA/160/NA | 76/89/44 | 384/341/414 | NA/NA/NA | NA/NA/NA |
| Oxygen demand | Room air/mechanical ventilation/mechanical ventilation | Nasal cannula/nasal high flow therapy/room air | Reservoir mask/mechanical ventilation/mechanical ventilation | Nasal cannula/nasal cannula/nasal cannula | Room air/room air/room air | Room air/room air/room air |
| No of infiltrated lung fields‡ | 4/6/6 | 5/5/0 | 6/6/6 | 6/6/0 | 5/5/0 | 4/4/0 |
| Treatment before escalation of the dose of TOF | GC, CY, TAC, TOF§, PE | GC, CY, TAC, TOF§, PE | GC, CY, TAC, TOF§, PE | GC, CY, TAC, TOF§, PE | GC, CY, TAC, TOF§ | GC, CY, TAC, TOF§ |
| Reasons for escalation of the dose of TOF | Worsening of dyspnoea, decreased P/F ratio, new GGO | Worsening of dyspnoea, decreased P/F ratio, new GGO | Worsening of dyspnoea, decreased P/F ratio, new GGO | Worsening of dyspnoea, decreased P/F ratio, new GGO | Worsening of dyspnoea and myalgia, elevated ferritin | Worsening of coughing and Gottron’s papule, elevated ferritin |
| Start of triple therapy* | Day 1 | Day 1 | Day 1 | Day 1 | Day 1 | Day 1 |
| Start of TOF 10 mg/day* | Day 14 | Day 6 | Day 10 | Day 34 | Day 11 | Day 19 |
| TOF escalation* | Day 34 | Day 15 | Day 17 | Day 63 | Day 35 | Day 45 |
| Clinical outcome | Dead (day 48, Respiratory failure due to RP-ILD) | Improved (dyspnoea, oxygen demanding, CT findings were improved) | Dead (Day 43, Respiratory failure due to RP-ILD) | Improved (dyspnoea, oxygen demanding, CT findings were improved) | Improved (dyspnoea, myalgia, ferritin were improved) | Improved (coughing, Gottron’s papule, ferritin were improved) |
| Discontinuation/reduction of TOF after improvement | NA | None | NA | Discontinued 16 months after escalation (due to infection) | None | Reduced to 10 mg/day 177 days after escalation (due to infection) |
| Infections | CMV reactivation | CMV reactivation, Herpes zoster | CMV reactivation | Herpes simplex keratitis | CMV reactivation (twice) | CMV reactivation (twice), Pulmonary aspergilloma |
*Baseline was defined as the date of starting immunosuppressive treatments for MDA5-DM (=day 1).
†Anti-MDA5 antibody was measured by the ELISA.
‡Numbers of infiltrated lung fields were scored as the extent of lung lesions. See the study of Kurasawa et al for detailed information.6
§The dose of TOF was 10 mg/day before escalation in all cases.
CMV, cytomegalovirus; CY, cyclophosphamide; F, female; GC, glucocorticoids; GGO, ground-grass opacity; KL-6, Krebs von den Lungen-6; M, male; MDA5, melanoma differentiation-associated protein 5; NA, not applicable; PE, plasma exchange; P/F ratio, PaO2/FiO2 ratio; RP-ILD, rapidly progressive interstitial lung disease; TAC, tacrolimus; TOF, tofacitinib.