Table 1

Patient’s characteristics at baseline and clinical course

Case number123456
Age/Sex71/F44/M58/M47/M47/F66/F
Observation period48 days16 months43 days19 months12 months8 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))393/288/777481/293/265622/338/571338/320/195269/342/199309/486/270
 CRP (0.00–0.14 (mg/dL))0.19/5.32/4.032.09/0.03/0.026.05/3.91/3.280.64/0.05/0.011.61/0.01/0.010.75/0.32/0.01
 Lymphocyte (825–3870 (/μL))186/134/105680/529/1348427/312/1091145/117/570266/93/2311165/243/1411
 KL-6 (<500 (U/mL))802/344/1370416/564/5261360/573/3242685/762/399434/1218/4861045/1337/923
 Ferritin (12.0–60.0 (ng/dL))1289/493/622960/2959/1341185/1592/1643852/295/2067/275/67791/943/55
 MDA5 Ab (<32 (Index))†2050/300/702200/2200/313700/950/3006650/900/53650/2700/213150/1350/30
 P/F ratio (mm Hg)350/220/64NA/160/NA76/89/44384/341/414NA/NA/NANA/NA/NA
 Oxygen demandRoom air/mechanical ventilation/mechanical ventilationNasal cannula/nasal high flow therapy/room airReservoir mask/mechanical ventilation/mechanical ventilationNasal cannula/nasal cannula/nasal cannulaRoom air/room air/room airRoom air/room air/room air
 No of infiltrated lung fields‡4/6/65/5/06/6/66/6/05/5/04/4/0
 Treatment before escalation of the dose of TOFGC, CY, TAC, TOF§, PEGC, CY, TAC, TOF§, PEGC, CY, TAC, TOF§, PEGC, CY, TAC, TOF§, PEGC, CY, TAC, TOF§GC, CY, TAC, TOF§
 Reasons for escalation of the dose of TOFWorsening of dyspnoea, decreased P/F ratio, new GGOWorsening of dyspnoea, decreased P/F ratio, new GGOWorsening of dyspnoea, decreased P/F ratio, new GGOWorsening of dyspnoea, decreased P/F ratio, new GGOWorsening of dyspnoea and myalgia, elevated ferritinWorsening of coughing and Gottron’s papule, elevated ferritin
 Start of triple therapy*Day 1Day 1Day 1Day 1Day 1Day 1
 Start of TOF 10 mg/day*Day 14Day 6Day 10Day 34Day 11Day 19
 TOF escalation*Day 34Day 15Day 17Day 63Day 35Day 45
 Clinical outcomeDead (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 improvementNANoneNADiscontinued 16 months after escalation (due to infection)NoneReduced to 10 mg/day 177 days after escalation (due to infection)
 InfectionsCMV reactivationCMV reactivation, Herpes zosterCMV reactivationHerpes simplex keratitisCMV 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.