A Randomized, Double-Blind, Placebo-Controlled Clinical Study on the Efficacy and Safety of Tocilizumab in the Treatment of Anti-MDA5 Antibody-Positive Adult Dermatomyositis
Phase: NA
Conditions: Dermatomyositis
Sponsor: Peking Union Medical College Hospital

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 A Randomized, Double-Blind, Placebo-Controlled Clinical Study 
on the Efficacy and Safety of Tocilizumab in the Treatment of 
Anti-MDA5 Antibody-Positive Adult Dermatomyositis 
 Clinical Trial Protocol 
 
 Primary Research Institution: Peking Union Medical College Hospital 
 Principal Investigator: Professor Wang Qian, Department of Rheumatology and Immunology, 
Peking Union Medical College Hospital 
 Date of Submission: December 4, 2025 
 
 
 Protocol Number: PROMIS-RCT-I 
 Version: 2.0 
 Version Date: December 4, 2025 
 
 Research Abstract 
 Study Title 
 A Randomized, Double-Blind, Placebo-Controlled Clinical Study on the Efficacy and 
Safety of Tocilizumab in the Treatment of Anti-MDA5 Antibody-Positive Adult 
Dermatomyositis 
 Study Drug 
 Tocilizumab Injection 
 Study Design 
 IIT 
 Study Design 
 A 16-week prospective, multicenter, randomized, double-blind, placebo-controlled 
clinical trial 
 

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 Treatment 
Regimen 
 Experimental Group: Standard of Care (SOC)* + Tocilizumab Injection (8 mg/kg, 
administered intravenously at Weeks 0, 2, 4, and 8 for a total of 4 doses) 
 Control Group: SOC + placebo injection intravenous infusion 
 *SOC: Prednisolone (<1 mg/kg/day) + one calcineurin inhibitor (Tacrolimus 1 mg bid 
or cyclosporine 3–5 mg/kg/day) 
 Study Endpoints 
 Primary Endpoints: 
 01) Proportion of patients achieving minimal improvement in Total Improvement 
Score (TIS≥20)  at Week 16 of treatment; 
 02) Change in PaO2/FiO2 ratio from baseline at Week 16 (patients with concomitant 
ILD). 
 Secondary Endpoints: 
 01) Proportion of patients achieving moderate (TIS ≥ 40) or major improvement (TIS 
≥ 60) in TIS at Week 16; 
 02) Change in Cutaneous Dermatomyositis Area and Severity Index (CDASI) score 
from baseline at Week 16 of treatment; 
 03) Change from baseline in Manual Muscle Testing (MMT-8) and Myositis Disease 
Activity Assessment Tool (MDAAT) Myositis disease activity assessment visual 
analogue scale (MYOACT) scores at Week 16; 
 04) The area under the curve (AUC) of glucocorticoid dose normalization over 16 
weeks; 
 05) Laboratory tests: Changes in serum ferritin and creatine phosphokinase (CK) at 
weeks 4, 8, and 16; 
 06) Proportion of patients who discontinued the study due to disease progression, 
investigator judgment requiring increased steroid dosage or immunosuppressant (dosage 
or type), or investigator judgment of ineffectiveness; 
 07) Safety indicators: Incidence of adverse events (AE) and serious adverse events 
(SAE), and proportion of patients who discontinued due to study drug-related adverse 
reactions. 

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 Exploratory study endpoints: 
 01) Changes in pulmonary function indices from baseline at Week 16: ΔFVC%, 
ΔFVC, ΔDLco%, ΔDLco; 
 02) Change in chest HRCT (High-Resolution Computed Tomography) score from 
baseline at Week 16; 
 03) Changes in oxygenation index (PaO2/FiO2) and peripheral oxygen saturation 
(SpO2) from baseline at Week 16; 
 04) Changes in lymphocyte count, ferritin, and pulmonary alveolar type II cell surface 
antigen-6 (KL-6) at Week 16. 
 Number of 
Subjects 
 A total of 110 subjects will be enrolled, with 55 in the experimental group and 55 in 
the control group 
 Study Procedure 
 1. Screening Period: Eligible subjects were screened according to inclusion and 
exclusion criteria. After signing the informed consent form, subjects undergo screening 
examinations within 14 days prior to the first dose and provide relevant information, 
including: demographic data, medical history/past medical history, medication history, 
height and weight, BMI, vital signs, physical examination, 12-lead electrocardiogram, 
clinical laboratory tests, myositis antibody panel, pulmonary function tests, and chest 
CT. 
2. Follow-up Period: Eligible subjects undergo randomization and receive study 
medication at Week 0, followed by protocol-based treatment. Center follow-up visits 
occur at Weeks 4, 8, and 16, with a telephone follow-up at Week 12. During treatment, 
subjects undergo scheduled assessments, clinical laboratory tests, and safety 
evaluations. 
 Inclusion 
Criteria 
 All inclusion criteria must be met for eligibility: 
 1.  Age ≥ 18 years and < 65 years; no gender restriction; total body weight ≥ 45 
kg; 
 2.  Diagnostic Criteria for Anti-MDA5-DM: Refer to the "2023 Chinese Expert 
Consensus on Diagnosis and Treatment of Anti-Melanoma Differentiation-Related 

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Gene 5 Antibody-Positive Dermatomyositis in China." Dermatomyositis patients 
exhibiting one of the following manifestations—Gottron's papules, Gottron's rash, or 
periorbital erythema—along with positive serum anti-MDA5 antibodies, may be 
diagnosed with anti-MDA5-DM; 
 3.  If patients have concomitant ILD, the following conditions must be met: i) Pulse 
oxygen saturation (SpO₂) ≥ 90% or PaO₂ ≥ 60 mmHg; ii) Pulmonary function 
tests showing forced vital capacity percentage of predicted (FVC%) ≥ 60% and 
carbon monoxide diffusion capacity percentage of predicted (DLco%) ≥ 40%; iii) 
High-resolution chest CT demonstrating pulmonary interstitial lesions involving < 50% 
of lung fields; 
 4.  Patients must have received oral prednisone (< 1 mg/kg/day, or equivalent dose 
of other glucocorticoids) for ≥ 4 weeks prior to randomization; 
 5.  Patients must have received a stable dose of a calcineurin inhibitor (CNI, such as 
cyclosporine or tacrolimus) for ≥4 weeks prior to randomization; if 
immunosuppressive therapy was discontinued prior to the screening visit, a washout 
period of at least 4 weeks is required; 
 6.  Patients must receive prophylactic treatment with trimethoprim-sulfamethoxazole 
(TMP-SMZ, 400mg trimethoprim/80mg sulfamethoxazole) 1-2 tablets daily during 
treatment; 
 7.  Women of childbearing potential must have a negative pregnancy test at study 
entry. If sexually active, they must agree to use effective contraception throughout the 
study period and must not intend to become pregnant during the study. 
 8.  Patients voluntarily participate in this study and sign an informed consent form. 
 Exclusion 
Criteria 
 Subjects meeting any of the following criteria will be excluded from the trial: 
 1.  Polymyositis, anti-synthetase syndrome, immune-mediated necrotizing myositis, 
or overlap myositis with other connective tissue diseases; 

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 2.  Patients with life-threatening complications, including but not limited to acute 
coronary syndrome (e.g., myocardial infarction, unstable angina) within 24 weeks prior 
to screening or any history of significant cerebrovascular disease; 
 3.  Any of the following laboratory abnormalities at screening: white blood cell 
count <3.0×10⁹/L, neutrophil count <1.0×10⁹/L, lymphocyte count <0.5×10⁹/L, 
hemoglobin <90 g/L, platelet count <50×10⁹/L; severe hepatic impairment (ALT or 
AST ≥3 times ULN, total bilirubin ≥1.5 times ULN, excluding serum ALT or AST 
elevation due to dermatomyositis); severe renal impairment (creatinine clearance ≤45 
mL/min); 
 4.  Patients hospitalized for severe infection within 60 days prior to screening, or 
who received intravenous antibiotics (patients who used intravenous antibiotics must 
complete a five-half-life washout period and confirm absence of active infection before 
enrollment), but may receive empirical oral antibiotics or topical antibiotics; 
 5.  Active tuberculosis infection that is untreated or inadequately treated; Latent 
tuberculosis infection (LTBI) requires at least 2 weeks of preventive antituberculosis 
therapy (including at least 2 antituberculosis drugs) prior to randomization, continuing 
through study completion. LTBI is defined as: Positive IGRA result (acceptable IGRA 
assays include: QFT-GIT, QFT-G, and T-spot® TB test); 
 6.  Active viral hepatitis at screening: HBsAg-positive, HBeAg-positive, or HBV-
DNA >10³ copies/L (HBV-DNA testing required if HBcAb-positive); HCVAb-
positive; 
 7.  Documented HIV infection, evidenced by positive serological test results or 
positive HIV serological test results at screening; 
 8.  If the patient develops ILD-related clinical manifestations or progressive 
radiographic worsening within 4 weeks, RP-ILD should be considered. RP-ILD is 
defined as the presence of any one of the following four conditions within 1 month 
after the onset of respiratory symptoms: ① Acute and progressive worsening of 
dyspnea requiring hospitalization or supplemental oxygen; ② Decline in pulmonary 
function, manifested as a decrease in FVC% >10% with or without a decrease in 

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DLco% >15%; ③ Increased interstitial abnormalities on chest HRCT scan >20%; ④ 
Decrease in arterial blood gas or partial pressure of oxygen >10 mmHg, indicating 
respiratory failure; and PaO₂/FiO₂≥200 mmHg. 
 9.  Allergy to the active ingredient tocilizumab or any of its excipients; 
 10.  Patients with sulfonamide allergy; 
 11.  Patients unable to complete pulmonary function testing at baseline; 
 12.  Patients receiving prednisone at a dose exceeding 2 mg/kg/day prior to screening; 
 13.  Patients receiving intravenous immunoglobulin (IVIG) prior to screening must 
discontinue treatment for at least 30 days; 
 14.  Patients who used one or more of the following medications within the specified 
time window prior to screening: 
 a)  Rituximab within 6 months prior to screening; 
 b)  JAK inhibitors within 2 weeks prior to screening; 
 c)  Use of other biologics (including but not limited to anakinra, adalimumab, 
infliximab) or other immunosuppressive agents (including but not limited to 
methotrexate, azathioprine, mycophenolate mofetil) within 4 weeks prior to screening; 
 15.  Patients with prior use of the study drug, other IL-6 inhibitors, or analogues; 
 16.  Pregnant or lactating women, or women planning to become pregnant or initiate 
lactation; 
 17.  History of malignant tumors within the past 5 years (excluding adequately treated 
basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical 
carcinoma in situ with no evidence of recurrence within the preceding 5 years); 
 18.  Other conditions deemed ineligible for study inclusion by the investigator. 
 
 
 

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A.  Principal Investigator Information 
Name 
 Wang Qian 
 Gender 
 Male 
Date of Birth 
 November 
1976 
Education 
 Doctoral Candidate 
 Degree 
 Doctorate 
Professional 
Title 
 Chief Physician 
 Position 
 Deputy Director 
 Email 
zhengaqian@126.com 
 Phone 
 13681211155 
 
B.  Research Background 
 Dermatomyositis (DM) is a chronic inflammatory autoimmune disease primarily affecting the 
skin and skeletal muscles. Anti-MDA5 antibody-positive dermatomyositis (anti-MDA5-DM) 
represents the most common and severe subtype of DM, characterized by ulcerative skin lesions and 
rapidly progressive interstitial lung disease (RP-ILD). The etiology and pathogenesis of anti-MDA5-
DM remain incompletely understood. Existing research suggests that genetic factors, viral infections, 
abnormal activation of the type I interferon pathway, and dysregulation of immune cell subsets may 
collectively contribute to its development. The disease can occur at any age but predominantly affects 
individuals aged 40–50 years, with a higher prevalence in women. Epidemiological data on anti-
MDA5-DM remains scarce in China. However, cohort studies indicate higher prevalence in Asian 
populations compared to Western populations, accounting for approximately 20%–50% of adult DM 
cases. In East Asia, approximately 60% to 80% of anti-MDA5-DM patients develop interstitial lung 
disease (ILD). Furthermore, recent studies have revealed a significant increase in anti-MDA5-DM 
incidence following the COVID-19 pandemic [1,2,3]. 
Anti-MDA5-DM is the subtype with the poorest prognosis in dermatomyositis, with acute 
respiratory failure due to RP-ILD being the primary cause of death. Current clinical management relies 
primarily on empirical regimens, lacking high-quality evidence-based medical support. 
Glucocorticoids serve as the cornerstone therapy, often combined with calcineurin inhibitors (e.g., 
cyclosporine, tacrolimus) for anti-MDA5-DM-related ILD [4,5]. However, even with intensive therapy 

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combining steroids and calcineurin inhibitors, approximately 50% of patients experience persistent 
ILD progression, with some requiring advanced life support [6,7]. Consequently, developing targeted 
therapies with proven efficacy represents an urgent clinical need. 
 Tocilizumab is a humanized monoclonal antibody targeting the IL-6 receptor, exerting 
therapeutic effects by specifically blocking the IL-6 signaling pathway [8]. Studies indicate that IL-6, 
as a key pro-inflammatory factor, plays a crucial role in the pathogenesis of anti-MDA5-DM, 
potentially directly mediating inflammatory responses and tissue damage processes [9]. Clinical 
observations reveal significantly elevated serum IL-6 levels in RP-ILD patients, with high IL-6 levels 
closely associated with poor patient outcomes [9]. Based on this, tocilizumab, by precisely inhibiting 
the IL-6 signaling pathway, can effectively control excessive inflammatory responses, improve clinical 
symptoms, and potentially delay disease progression, offering a new targeted therapeutic option for 
anti-MDA5-DM treatment. 
 Currently, approved indications for tocilizumab worldwide do not include anti-MDA5-DM. 
Therefore, its use in treating anti-MDA5-DM constitutes off-label use. Our research team was the first 
internationally to report the clinical efficacy of tocilizumab in treating anti-MDA5-DM. Among 6 
patients with anti-MDA5-DM complicated by ILD who responded poorly to conventional 
corticosteroid plus immunosuppressive therapy, 5 (83.3%) demonstrated significant improvement in 
respiratory symptoms and pulmonary imaging findings after adding tocilizumab, confirming the 
treatment regimen's favorable efficacy and safety profile [10]. Subsequent case reports further 
validated these findings, providing crucial evidence for tocilizumab's application in anti-MDA5-DM 
therapy [11,12]. 
 Currently, the potential efficacy of tocilizumab in anti-MDA5-DM treatment has garnered 
attention in multiple domestic and international expert consensus statements. These consensus 
documents suggest considering its inclusion in treatment regimens for dermatomyositis, particularly 
anti-MDA5-DM cases [2,5,13]. However, as existing studies are predominantly small-sample case 
reports or case series lacking evidence from rigorously designed randomized controlled trials (RCTs), 
these consensus documents maintain a cautious stance without issuing explicit recommendations. To 
confirm the clinical value of tocilizumab, large-scale, multicenter clinical studies are still needed to 

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systematically evaluate its precise efficacy and long-term safety, thereby providing more reliable 
evidence-based medical support for clinical practice. Therefore, this study proposes to conduct a 
prospective, multicenter, randomized, placebo-controlled clinical trial to further provide high-quality 
evidence on the efficacy and safety of tocilizumab in treating anti-MDA5-DM. This is expected to 
address the current lack of definitively effective treatments for this disease and offer a new therapeutic 
option for this rare but severely debilitating autoimmune disorder. 
 
C.  Study Objectives 
 Through a 16-week, multicenter, prospective, randomized, placebo-controlled clinical trial, this 
study aims to systematically evaluate the efficacy and safety of tocilizumab in treating Chinese adult 
patients with anti-MDA5-DM, thereby providing high-quality clinical evidence for its clinical 
application in this disease. If this study confirms the efficacy and safety of tocilizumab for anti-MDA5-
DM, it will help address the current lack of therapeutic options for this disease. It holds promise as a 
new treatment choice for anti-MDA5-DM, potentially improving treatment standards, reducing patient 
mortality, enhancing quality of life, alleviating the burden on families and society, and saving 
healthcare costs. 
 
D.  Research Methods and Content 
1.  Study Design 
 This study will conduct a 16-week prospective, multicenter, randomized, placebo-controlled 
clinical trial. It aims to enroll 110 Chinese adult patients with anti-MDA5-DM. Patients will be 
stratified based on whether their PaO₂/FiO₂ ratio is less than 300 mmHg. Within each stratum, patients 
will be randomly assigned in a 1:1 ratio to either the treatment group or the control group. The specific 
medication regimens for each group are as follows: 
 Experimental Group: Standard treatment regimen combined with tocilizumab injection (8 mg/kg 
administered intravenously at weeks 0, 2, 4, and 8 for a total of 4 doses) 
 Control group: Standard treatment regimen combined with placebo intravenous infusion 

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 The standard treatment regimen consists of prednisone (<1 mg/kg/day) combined with one 
calcineurin inhibitor (tacrolimus 1 mg bid or cyclosporine 3-5 mg/kg/day). 
 Permitted concomitant medications: During the study treatment period, necessary treatments may 
be provided by the investigator based on routine clinical practice for the benefit of the subject. The 
following medications/treatments may be used as appropriate: medications for hypertension, diabetes, 
etc. During concomitant use, the following must be recorded: drug name (generic and brand name), 
daily dosage, route of administration, start and end dates of use, and reason for use. 
 Criteria for discontinuation of study drug: Occurrence of a serious adverse event (SAE) related 
to the study drug, such as life-threatening or fatal events, severe infection, severe allergic reaction (e.g., 
anaphylaxis) or infusion reaction, clinically significant severe laboratory abnormalities, or any 
circumstance where the investigator deems the risk of continued treatment outweighs the benefit for 
the subject's safety. 
 The study will be conducted using a double-blind method, with neither the subjects nor the 
clinicians aware of the study group assignment. The randomization protocol will be generated via an 
electronic IWRS system, which will not disclose any information regarding treatment allocation to the 
investigators or any personnel responsible for conducting the study or analyzing the data. The results 
of randomization may only be reported to the hospital pharmacist or designated personnel in the 
specified manner; other trial personnel shall not have access to this information. 
 Study Procedure: 1) Screening Period: Eligible subjects are screened according to inclusion and 
exclusion criteria. After signing informed consent, subjects undergo screening examinations within 14 
days prior to first dosing and provide relevant information, including: demographic data, medical 
history/past medical history, medication history, height/weight, BMI, vital signs, physical examination, 
12-lead ECG, clinical laboratory tests, myositis antibody panel, pulmonary function tests, and chest 
CT. 2) Follow-up Period: Eligible subjects randomized at Week 0 to receive study drug and undergo 
protocol-defined treatment. Center follow-up visits occur at Weeks 4, 8, and 16, with a telephone 
follow-up at Week 12. During treatment, subjects undergo scheduled assessments, clinical laboratory 
tests, and safety evaluations. 
 Primary endpoints include: 1) Proportion of patients achieving TIS minimal improvement (TIS ≥ 
20) at Week 16 (TIS: Total Improvement Score as defined by the International Myositis Assessment 

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and Clinical Study Group (IMACS); TIS minimal improvement defined as TIS score ≥ 20); 2) 
Change in PaO₂/FiO₂ from baseline at Week 16 (patients with concomitant ILD). Secondary endpoints 
included: 1) Proportion of patients achieving moderate (TIS ≥ 40) or major improvement (TIS ≥ 60) 
at Week 16; 2) Change in the Cutaneous and Muscular Dermatomyositis Area and Severity Index 
(CDASI) score from baseline at Week 16; 3) Change in Manual Muscle Testing (MMT-8) and Muscle 
Disease Activity Assessment Tool (MDAAT) Myositis disease activity assessment visual analogue 
scale (MYOACT) scores from baseline at Week 16; 4) Glucocorticoid dose-normalized AUC over 16 
weeks; 5) Laboratory tests: Changes in serum ferritin and creatine phosphokinase (CK) at weeks 4, 8, 
and 16; 6) Proportion of patients who discontinued the study due to disease progression, investigator 
judgment requiring increased glucocorticoid dose or immunosuppressant (dose or type), or investigator 
judgment of treatment failure; 7) Safety measures: incidence of adverse events (AE) and serious 
adverse events (SAE), and proportion of patients withdrawing due to study drug-related adverse 
reactions. Exploratory measures: 1) Changes in pulmonary function parameters at Week 16 compared 
to baseline: ΔFVC%, ΔFVC, ΔDLco%, ΔDLco; 2) Change in chest HRCT score at Week 16 compared 
to baseline; 3) Changes in oxygenation index (PaO₂/FiO₂) and oxygen saturation (SpO₂) at Week 16 
compared to baseline; 4) Changes in lymphocyte count, ferritin, and pulmonary alveolar type II cell 
surface antigen-6 (KL-6) at Week 16. 
 
2.  Study Population 
 2.1 Inclusion Criteria (all criteria must be met): 
1. 
 Age ≥18 years and <65 years, male or female; total body weight ≥45 kg; 
2. 
 Anti-MDA5-DM Diagnostic Criteria: Refer to the "2023 Chinese Expert Consensus on 
Diagnosis and Treatment of Anti-Melanocyte Differentiation-Related Gene 5 Antibody-
Positive Dermatomyositis in China." Dermatomyositis patients exhibiting one of the 
following manifestations—Gottron's papules, Gottron's rash, or erythema ab igne—along 
with positive serum anti-MDA5 antibodies, meet the criteria for anti-MDA5-DM diagnosis. 
3. 
 If the patient has concomitant ILD, the following conditions must also be met: i) Pulse 
oxygen saturation (SpO₂) ≥90% or PaO₂ ≥ 60 mmHg; ii) Pulmonary function tests showing 

12 
 
forced vital capacity percentage of predicted (FVC%) ≥ 60% and carbon monoxide diffusion 
capacity percentage of predicted (DLco%) ≥ 40%; iii) High-resolution chest CT 
demonstrating pulmonary interstitial lesions involving < 50% of lung fields; 
4. 
 Patients must have received oral prednisone (< 1 mg/kg/day, or equivalent dose of other 
glucocorticoids) for ≥ 4 weeks prior to randomization. 
5. 
Patients must have received a stable dose of a calcineurin inhibitor (CNI, such as cyclosporine 
or tacrolimus) for ≥4 weeks prior to the randomization visit; If immunosuppressive drugs 
were discontinued prior to the screening visit, a washout period of at least 4 weeks is required 
(specifically, for immunosuppressive drugs such as methotrexate, azathioprine, or 
mycophenolate mofetil, a complete discontinuation period of at least 4 weeks must be 
observed between the last dose of the immunosuppressive drug and the randomization visit 
to ensure elimination of drug effects); 
6. 
 Patients must take co-trimoxazole (TMP-SMZ: trimethoprim 400mg/sulfamethoxazole 
80mg) for infection prophylaxis during treatment, 1-2 tablets daily; 
7. 
 Women of childbearing potential must have a negative pregnancy test at study entry. If 
sexually active, they must agree to use effective contraception throughout the study period 
and must not intend to become pregnant during the study; 
8. 
 Patients voluntarily participate in this study and sign an informed consent form. 
 
 2.2 Exclusion Criteria (Subjects meeting any of the following criteria will be excluded from the 
trial): 
1.  Polymyositis, anti-synthetase syndrome, immune-mediated necrotizing myositis, or overlap 
myositis with other connective tissue diseases; 
2.  Patients with life-threatening complications, including but not limited to acute coronary 
syndrome (e.g., myocardial infarction, unstable angina) within 24 weeks prior to screening or 
any history of significant cerebrovascular disease; 
3.  Any of the following laboratory abnormalities at screening: white blood cell count <3.0 × 
10⁹/L, neutrophil count <1.0 × 10⁹/L, lymphocyte count <0.5 × 10⁹/L, hemoglobin <90 g/L, 

13 
 
platelet count <50 × 10 9/L; severe hepatic impairment (ALT or AST ≥3 times ULN, total 
bilirubin ≥1.5 times ULN, excluding serum ALT or AST elevation due to dermatomyositis); 
severe renal impairment (creatinine clearance ≤45 ml/min); 
4.  Hospitalization for severe infection within 60 days prior to screening, or intravenous 
antibiotic administration (patients receiving IV antibiotics must complete a five-half-life 
washout period and confirm absence of active infection before enrollment); patients may 
receive empirical oral antibiotics or topical antibiotics; 
5.  Untreated or inadequately treated active tuberculosis infection; Latent tuberculosis infection 
(LTBI) requires at least 2 weeks of preventive antituberculosis therapy (including at least 2 
antituberculosis drugs) prior to randomization, continuing through study completion. LTBI is 
defined as: Positive IGRA result (acceptable IGRA assays include: QFT-GIT, QFT-G, and T-
spot® TB test); 
6.  Active viral hepatitis at screening: HBsAg-positive, HBeAg-positive, or HBV-
DNA >10³copies/L in serum; HBV-DNA testing required if HBcAb-positive; HCVAb-
positive; 
7.  Documented HIV infection, evidenced by positive serology results or positive HIV serology 
at screening; 
8.  If a patient develops ILD-related clinical manifestations or progressive radiographic 
worsening within 4 weeks, RP-ILD should be considered. RP-ILD is defined as meeting any 
one of the following four criteria within 1 month after onset of respiratory symptoms: ① 
Acute and progressive worsening of dyspnea requiring hospitalization or supplemental oxygen; 
② Decline in pulmonary function, manifested as a decrease in FVC% >10% with or without 
a decrease in DLco% >15%; ③ Increased interstitial abnormalities on chest HRCT scan >20%; 
④ Decrease in arterial blood gas analysis or partial pressure of oxygen (PaO₂)>10 mmHg, 
indicating respiratory failure; and PaO₂/FiO₂≥200 mmHg; 
9.  Allergy to the active ingredient tocilizumab or any of its excipients; 
10.  Patients with sulfonamide allergy; 
11.  Patients unable to complete pulmonary function testing at baseline; 
12.  Patients receiving prednisone therapy at a dose exceeding 2 mg/kg/day prior to screening; 

14 
 
13.  Patients who received intravenous immunoglobulin (IVIG) prior to screening must 
discontinue treatment for at least 30 days; 
14.  Patients who used one or more of the following medications within the specified time 
window prior to screening: 
a)  Rituximab within 6 months prior to screening; 
b)  JAK inhibitors within 2 weeks prior to screening; 
c)  Other biologics (including but not limited to anakinra, adalimumab, infliximab) and 
other immunosuppressive agents (including but not limited to methotrexate, azathioprine, 
mycophenolate mofetil) within 4 weeks prior to screening; 
15.  Patients with prior exposure to the study drug, other IL-6 inhibitors, or analogues; 
16.  Pregnant or lactating women, or women planning pregnancy or initiating lactation; 
17.  History of malignant tumors within the past 5 years (excluding adequately treated basal cell 
carcinoma of the skin, squamous cell carcinoma of the skin, or cervical carcinoma in situ with 
no evidence of recurrence within the preceding 5 years); 
18.  Other conditions deemed ineligible for study inclusion by the investigator. 
 
 2.3 Withdrawal Criteria 
 During the study, participants may voluntarily withdraw from the trial at any time for any reason. 
Investigators may also decide to withdraw a participant from the trial if unacceptable risks or other 
circumstances arise. Specific reasons may include: 
1. 
 The subject requests withdrawal from the trial; 
2. 
 Pregnancy of the subject; 
3. 
 Progression of the subject's disease or occurrence of a serious adverse reaction; 
4. 
 Participation in another clinical trial during the study period; 
5. 
 Other circumstances where the investigator deems the subject unsuitable for continued 
participation in the study. 
 
3.  Sample Size Calculation 

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 The primary endpoint of this study is the proportion of subjects achieving a minimum 
improvement in TIS (TIS ≥ 20). For the subgroup of patients with concomitant ILD, the primary 
endpoint is the change in PaO₂/FiO₂ from baseline. To control Type I error, the significance level for 
the TIS≥20 analysis is set at 0.025 (two-tailed), and the significance level for the PaO₂/FiO₂ analysis 
is also set at 0.025 (two-tailed). The study will be considered positive if either the TIS≥20 analysis or 
the PaO₂/FiO₂ analysis yields statistically significant results. 
 Sample size was calculated based on the proportion of subjects achieving the primary endpoint 
of minimal TIS improvement (TIS ≥ 20). Previous studies reported a range of 25%–30% for subjects 
achieving minimal TIS improvement with standard polymyositis therapy, and 66%–79% for subjects 
achieving minimal TIS improvement with biologics or JAK inhibitors combined with standard therapy. 
Considering clinical efficacy, this study hypothesizes that 25% of subjects in the placebo group will 
achieve the minimum TIS improvement at Week 12, and 65% in the TCZ treatment group (i.e., a 40% 
between-group difference), with a two-sided α level of 0.025 and 90% power. At least 74 subjects are 
required to demonstrate a significant difference in primary efficacy between the TCZ and placebo 
groups. Accounting for a 20% dropout rate, a total of 94 subjects must be enrolled, equating to 47 
subjects per group. 
[Comment: Update to 'Week 16' for consistency with trial duration.] 
 Sample size calculation based on the expected change inPaO₂/FiO₂from baseline. Clinical experience 
suggests that the change in PaO₂/FiO₂ after treatment can reach 100 mmHg, with one-third of this 
change considered a clinically significant difference. Assuming a between-group difference of 30 
mmHg in the change in PaO₂/FiO₂ from baseline at Week 12, with a standard deviation of 25 mmHg, 
a two-sided α level of 0.025, and 90% power, at least 38 subjects are required to demonstrate a 
significant difference in primary efficacy between the TCZ and placebo groups. Accounting for a 20% 
dropout rate, a total of 48 subjects will ultimately be required, equating to 24 subjects per group. 
 This study plans to conduct one interim analysis and one final analysis. The interim analysis will 
occur after 55 patients are enrolled. The Haybittle-Peto method will be used to control Type I error at 
0.025 (two-sided). If the interim analysis results for TIS ≥ 20 or PaO₂/FiO₂ reject the null hypothesis 
(two-sided p-values both < 0.001), the endpoint will be declared reached. If the interim analysis fails 

16 
 
to reject the null hypothesis, the final analysis will test TIS ≥ 20 and PaO₂/FiO₂ at a 0.025 (two-sided) 
significance level. Therefore, accounting for alpha expenditure from the interim analysis, the sample 
size is increased by 15% from the original plan, resulting in a final target enrollment of 110 subjects. 
 
4.  Statistical Analysis 
 The statistical analysis plan will be initiated prior to study completion and finalized before 
database lock. The plan will detail all statistical analyses to be performed, including definitions of 
datasets and algorithms for data derivation, as well as descriptive and analytical methods for various 
outcomes. Statistical analyses will be conducted using IBM SPSS software (version 25.0 or higher). 
Quantitative data will be described using mean, median, standard deviation, maximum, and minimum 
values. Categorical or ordinal data will be presented as case counts and percentages. (1) Case Analysis: 
Describe trial completion status, with statistical descriptions for each excluded or withdrawn case. (2) 
Demographic and Baseline Analysis: Describe demographic characteristics and other baseline 
indicators of enrolled patients. Baseline data include gender, age, etc. (3) Endpoint analysis: Conduct 
efficacy outcome analysis based on both the FAS and PPS datasets. (4) Safety analysis: List the number 
of cases and occurrences of AEs and SAEs (NCICTCAE v5.0), calculate incidence rates, and report 
the proportion of patients who discontinued due to study drug-related adverse reactions. 
 
5.  Follow-up Schedule 
             Time 
  
 
Item  
 
Screening 
Period 
 Observation Period 
 
 -14 to 0 
days 
 
Randomization 
 Visit 1 
 Visit 2 
 Visit 3 
(Telephone) 
 Visit 4 
 
4 weeks ± 3 
days 
 8 weeks ± 3 
days 
 12 weeks ± 3 
days 
 16 weeks ± 
3 days 
 
 Informed Consent 
 X 
 
 
 
 
 
 
 Inclusion/Exclusion 
Criteria 
 X 
 
 
 
 
 
 
 General Information and 
Medical History 
Collection A 
 X 
 
 
 
 
 
 

17 
 
 Vital Signs B 
 X 
 X 
 X 
 X 
 
 X 
 
 Physical Examination C 
 X 
 X 
 X 
 X 
 
 X 
 
 Complete Blood Count 
D 
 X 
 X 
 X 
 X 
 
 X 
 
 Liver and Kidney 
Function E 
 X 
 X 
 X 
 X 
 
 X 
 
 C-reactive protein 
(CRP), erythrocyte 
sedimentation rate (ESR) 
 
 X 
 X 
 X 
 
 X 
 
 Serum ferritin 
 
 X 
 X 
 X 
 
 X 
 
 Creatine Kinase (CK) 
 
 X 
 X 
 X 
 
 X 
 
 Arterial Blood Gas 
Analysis 
 
 X 
 
 
 
 X 
 
 Prednisone Dosage 
 
 X 
 X 
 X 
 X 
 X 
 
 MYOACT, TIS Score F 
 
 X 
 X 
 X 
 
 X 
 
 Skin CDASI Score G 
 
 X 
 X 
 X 
 
 X 
 
 Pulmonary Function 
Tests: FVC%, FVC, 
DLco%, DLco 
 X 
 
 
 
 
 X 
 
 Chest HRCT 
 X 
 
 
 
 
 X 
 
 Oxygenation Index 
(PaO₂/FiO₂), Blood Oxygen 
Saturation (SpO₂) 
 X 
 
 X 
 X 
 
 X 
 
 Alveolar Type II Cell 
Surface Antigen-6 (KL-6) 
 
 X 
 
 
 
 X 
 
 12-lead 
electrocardiogram ECG 
 X 
 
 X 
 X 
 
 X 
 
 Research drug use I 
 
 X 
 X 
 X 
 X 
 X 
 
 Combination Therapy 
 X 
 X 
 X 
 X 
 X 
 X 
 
 AE/SAE 
 
 X 
 X 
 X 
X 
 X 
 
 Safety Assessment 
 
 X 
 X 
 X 
 X 
 X 
 
 Adverse Event 
Correlation Assessment 
 
 X 
 X 
 X 
 X 
 X 
 
 A.  General information includes name, age, gender, ethnicity, height, weight, BMI, etc.; medical history 
includes: current medical history, past medical history, medication history, allergy history, medication history, 
etc. 
 B.  Vital signs include temperature, pulse, respiration, and blood pressure, with specific details determined 
by the investigator's comprehensive assessment. 
 C.  Physical examination includes skin, mucous membranes, lymph nodes, head, neck, chest, abdomen, 
spine/extremities, and other areas. 

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 D.  Complete blood count includes lymphocytes, white blood cells, red blood cells, hemoglobin, 
neutrophils, platelets, etc. 
 E.  Liver and kidney function: including alanine aminotransferase, aspartate aminotransferase, total protein, 
creatinine clearance, and urine protein. 
 F.  TIS Score: Total Improvement Score of the ACR/EULAR Criteria for Myositis Response. 
 G.  CDASI Score: Cutaneous Dermatomyositis Area and Severity Index Score. 
 H.  12-lead electrocardiogram including heart rate (P), P-R interval, QRS interval, Q-T interval, etc. 
 I.  During medication administration, closely monitor for drug reactions. 
 
6.  Study Termination 
 Study termination refers to the premature cessation of an entire clinical trial before all subjects 
have been evaluated according to the protocol. The entire trial or a specific study site may be 
terminated early if any of the following conditions occur: 
1.  New, conclusive evidence indicating an unfavorable risk-benefit assessment of the 
investigational drug, such as unacceptable safety concerns; 
2.  Slow subject enrollment at a study site, preventing completion within an acceptable 
timeframe; 
3.  The investigator deems continuation of the trial inappropriate for medical, ethical, or other 
reasons; 
4.  The ethics committee terminates the trial for any reason. 
5.  If interim analysis results yield definitive conclusions regarding efficacy and safety, and 
continuation of the study would not alter the final conclusions, the investigator will terminate 
the study early. 
 
E.  Risk/Benefit Assessment 
1.  Known Potential Risks 
 All studies carry known and unknown risks. Tocilizumab is approved for treating rheumatoid 
arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome, with its safety and 

19 
 
efficacy fully validated in these patient populations. Major adverse reactions reported in clinical studies 
include: risk of viral and bacterial infections, allergic rash, elevated liver enzymes and bilirubin, and 
granulocytopenia. 
 Anti-MDA5-DM therapy carries a risk of rapid progressive interstitial lung disease (RP-ILD), 
which may lead to respiratory failure or even be life-threatening. While this risk exists for some 
patients in this study, it is inherent to the disease progression and has been widely documented. This 
study will implement rigorous follow-up monitoring to detect and address this risk as early as possible. 
Should signs of respiratory failure emerge, investigators may terminate the study at any time and 
provide active treatment based on clinical need. An interim analysis is planned to assess related risks 
and determine whether to terminate the study early. 
2.  Known Potential Benefits 
 Tocilizumab injection is an approved recombinant humanized anti-human interleukin-6 (IL-6) 
receptor monoclonal antibody with established efficacy and safety. By precisely inhibiting the IL-6 
signaling pathway, tocilizumab effectively controls excessive inflammatory responses and improves 
clinical symptoms, offering a promising new targeted therapeutic option for anti-MDA5-DM treatment. 
In our team's prior clinical practice, among 6 anti-MDA5-DM patients with ILD who responded poorly 
to conventional corticosteroid plus immunosuppressive therapy, 5 (83.3%) demonstrated significant 
improvement in respiratory symptoms and pulmonary imaging findings after adding tocilizumab. 
Subsequent case reports from multiple domestic and international sources further validated this finding, 
providing crucial evidence for the potential benefits of tocilizumab in anti-MDA5-DM therapy. 
Through rigorous trial design, this study offers patients follow-up monitoring at a higher frequency 
than standard clinical practice, along with more standardized and detailed assessment protocols and 
access pathways. This facilitates close monitoring of patient conditions and timely intervention. 
3.  Assessment of Potential Risks and Benefits 
 Tocilizumab has demonstrated overall controllable risks and clear clinical benefits within its 
approved indications. For the specific population receiving anti-MDA5-DM therapy, while known 
drug-related adverse reaction risks exist, these risks are largely predictable, monitorable, preventable, 

20 
 
and manageable. The study protocol established strict inclusion/exclusion criteria for major risks 
(particularly infections), excluding high-risk patients such as those with active infections or severe 
hepatic/renal impairment, alongside a comprehensive monitoring plan (including regular vital signs, 
CBC, hepatic/renal function, and AE assessments). Concurrently, existing mechanisms and clinical 
evidence strongly suggest that tocilizumab offers significant potential benefits in this population, 
particularly in improving pulmonary lesions and clinical symptoms. This is crucial for enhancing the 
prognosis of patients at high risk of mortality. Given the severity and rapid progression of anti-MDA5-
DM disease itself, along with the limited treatment options for patients unresponsive to conventional 
therapies, the potential clinical benefits of using tocilizumab under close monitoring and management 
are expected to significantly outweigh its known and controllable risks. This randomized controlled 
trial design will provide higher-level evidence-based medical evidence, ultimately quantifying the risk-
benefit ratio in this specific population to guide future clinical practice and enable patients to receive 
more scientifically effective treatment. 
[Comment: Simplify to 'This randomized controlled trial will provide high-level evidence.'] 
 Therefore, the benefits of this study outweigh the risks. 
F.  Expected Outcomes 
 Through a rigorous clinical study design, this research will systematically evaluate the efficacy 
and safety of tocilizumab in treating patients with mild-to-moderate anti-MDA5 antibody-positive 
dermatomyositis. It aims to provide high-quality evidence-based medical evidence, offering new 
therapeutic options for clinical practice. The findings are expected to be published in internationally 
renowned academic journals and translated into clinical applications, thereby improving patients' 
quality of life, reducing disease burden, and yielding significant social and economic benefits. 
 
G.  Data Retention and Confidentiality 
 Confidentiality of subject information is strictly enforced by the principal investigator, 
participating researchers, the sponsor, and its agents. Confidentiality extends beyond clinical 

21 
 
information to include biological samples. Consequently, the study protocol, documentation, data, and 
all other information generated will be kept strictly confidential. No research or data information may 
be disclosed to any unauthorized third party without the sponsor's prior written approval. Other 
authorized representatives of the sponsor, the Ethics Committee, and regulatory authorities may 
inspect all documents and records required to be maintained by the investigator, including but not 
limited to medical records and subject medication records. The study site shall permit access to these 
records. Subject contact information will be securely stored at each study site and used solely for 
internal purposes during the study. Upon study completion, all records will continue to be stored 
securely for the duration specified by the local Ethics Committee and applicable regulations. Research 
data collected from subjects for statistical analysis and scientific reporting will be uploaded and stored 
at the research center. This data shall not include subject contact information or personally identifiable 
information. Instead, subjects and their research data will be assigned unique study identification 
numbers. The research data entry and management systems used by investigators at each clinical 
research center are confidential and password-protected. At the conclusion of the study, all identifying 
information from the research databases will be removed and archived at the research center. 
 
H.  Informed Consent 
 Each subject (or their legal representative) must provide written consent after fully 
understanding the purpose and content of the study. This written consent must be signed (with signature 
and date) before any trial-related procedures are performed. The informed consent form should comply 
with the Declaration of Helsinki, current GCP guidelines, and applicable regulations. 
 Prior to potential subject enrollment, the investigator or authorized personnel shall explain the 
study's purpose, methods, potential benefits, possible risks, and any anticipated discomfort. Subjects 
shall be informed that participation is voluntary and may be withdrawn at any time. If a subject declines 
to participate, alternative treatments remain available, and the decision to participate shall not affect 
their disease management. Finally, subjects should understand that the investigator will maintain their 
identity records for long-term follow-up as needed. These records may be reviewed by regulatory 
authorities and the sponsor within the scope permitted by relevant laws and regulations. Subject 

22 
 
privacy will be protected. By signing the informed consent form, the subject authorizes the 
aforementioned actions. 
 The subject (or their legal representative) shall be given sufficient time to read the informed 
consent form and ask questions. After the investigator's explanation and prior to the subject's 
enrollment, the subject (or their legal representative) shall sign their name and date on the informed 
consent form for the record. Following the signing of the informed consent form, the subject shall 
receive a copy of the form. 
 If the subject (or their legal representative) cannot read or write, an impartial witness should 
participate in the entire informed consent process (including reading and explaining all written 
information) and personally sign their name and date after the subject (or their legal representative) 
gives verbal consent. 
 Subjects who cannot understand the content of the informed consent form may only participate 
in the trial after their legal representative has provided informed consent. 
 
I. 
 Research Quality Control 
 1. Data Quality Assurance 
 A Data Management Plan (DMP) shall be developed prior to data collection, detailing 
procedures for data collection, cleaning, and consistency checks. Data management processes shall 
follow the Data Management Company's Standard Operating Procedures (SOPs). Electronic Data 
Capture (EDC) systems will be used for data collection. Adverse events (AEs) will be medically coded 
using the MedDRA regulatory medical vocabulary. The database will be locked when all data has been 
cleaned, queries resolved, medical coding completed, protocol deviations and any issues identified 
during data list review addressed, and the investigator has completed electronic signatures on the eCRF. 
 Data management is performed by the Data Management Company. The Data Management Plan 
(DMP) is authored by the Data Manager (DM) as the guiding document for the entire data management 
process. All data management procedures shall be conducted according to the timelines, content, and 
methods defined therein. The DMP is a dynamic document subject to revision and updates during the 
trial based on actual circumstances. 
 This study employs an Electronic Data Capture (EDC) system for data collection and 

23 
 
management. Data managers design data capture forms according to protocol requirements, including 
study visits, form names, and data items collected. They configure data validation programs (DVP) 
based on the DVP plan, test these programs, and release them for use after investigator approval. The 
investigator or their authorized clinical research coordinator (CRC) accesses the data management 
system via a separate account. They accurately, timely, completely, and consistently complete the 
electronic case report form (eCRF) based on source documentation and eCRF completion guidelines. 
The investigator or their authorized personnel are responsible for performing 100% source data 
verification (SDV) of the information entered into the database. After data entry is completed and SDV 
is performed, the investigator confirms with an electronic signature. Any revisions to signed data 
require re-signature. After confirming the completeness and accuracy of database entries, the database 
is locked by the data management personnel following joint approval from the investigator, data 
management personnel, and statistical analysts. 
 2. Investigator Training 
 Investigators participating in this study must possess professional qualifications and capabilities, 
pass qualification reviews, and remain consistent throughout the study. Prior to study initiation, the 
principal investigator will conduct regular in-person and online training sessions for investigators at 
all participating sites in this multicenter study. This ensures investigators fully understand the study 
protocol and procedures, guaranteeing consistency in study-related assessment operations. 
 3. Preservation of Original Data 
 Essential clinical trial documents refer to records that evaluate the conduct and data quality of a 
clinical trial, serving as evidence that the investigator complied with relevant laws and regulations 
governing drug clinical trials throughout the study. 
 Both the investigators and clinical trial sites confirm they have suitable facilities and conditions 
for storing essential clinical trial documents. Storage equipment must prevent direct light exposure, 
water damage, and fire hazards to facilitate long-term preservation. In accordance with protocol 
requirements, stored documents must be readily identifiable, retrievable, accessible, and archivable. 
Storage media for clinical trial materials must ensure the integrity and readability of original data or 
certified copies throughout the retention period. Regular testing or verification of data recovery 
capability must be conducted to prevent intentional or unintentional alteration or loss. 

24 
 
 Certain documents generated during clinical trial implementation, if not listed in the clinical trial 
essential document management directory, may also be included in the respective essential document 
archives of the investigator and clinical trial site based on necessity and relevance. 
 At the start of the clinical trial, the investigator must establish a critical document file 
management system. At the conclusion of the trial, critical documents are reviewed and confirmed, 
and these documents are properly preserved. 
 
J. 
 References 
1.  LU X, PENG Q, WANG G. Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical 
progress [J]. Nat Rev Rheumatol, 2024, 20(1): 48-62. 
2.  Lu Xin, Peng Qinglin, Shu Xiaoming, et al. Chinese Expert Consensus on Diagnosis and Treatment of 
Anti-MDA5 Antibody-Positive Dermatomyositis (2023 Edition) [M]. 2024. Chinese Journal of 
Rheumatology, 2024, 28(01): 5-14.  
3.  MCPHERSON M, ECONOMIDOU S, LIAMPAS A, et al. Management of MDA-5 antibody positive 
clinically amyopathic dermatomyositis associated interstitial lung disease: A systematic review [J]. Semin 
Arthritis Rheum, 2022, 53: 151959. 
4.  FUJISAWA T, HOZUMI H, KAMIYA Y, et al. Prednisolone and tacrolimus versus prednisolone and 
cyclosporin A to treat polymyositis/dermatomyositis-associated ILD: A randomized, open-label trial [J]. 
Respirology, 2021, 26(4): 370-7. 
5.  ROMERO-BUENO F, DIAZ DEL CAMPO P, TRALLERO-ARAGUÁS E, et al. Recommendations for 
the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated 
rapidly progressive interstitial lung disease [J]. Semin Arthritis Rheum, 2020, 50(4): 776-90. 
6. CHEN Z, WANG X, YE S. Tofacitinib in Amyopathic Dermatomyositis-Associated Interstitial Lung 
Disease [J]. N Engl J Med, 2019, 381(3): 291-3. 
7.  HE W, CUI B, CHU Z, et al. Radiomics based on HRCT can predict RP-ILD and mortality in anti-MDA5⁺ 
dermatomyositis patients: a multi-center retrospective study [J]. Respir Res, 2024, 25(1): 252. 
8.  SCOTT L J. Tocilizumab: A Review in Rheumatoid Arthritis [J]. Drugs, 2017, 77(17): 1865-79. 
9.  NARA M, KOMATSUDA A, OMOKAWA A, et al. Serum interleukin 6 levels as a useful prognostic 
predictor of clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease [J]. 
Modern Rheumatology, 2014, 24(4): 633-6. 
10.  ZHANG X, ZHOU S, WU C, et al. Tocilizumab for refractory rapidly progressive interstitial lung disease 
related to anti-MDA5-positive dermatomyositis [J]. Rheumatology (Oxford), 2021, 60(7): e227-e8. 
11.  WANG Q H, CHEN L H. Treatment of refractory anti-melanoma differentiation-associated gene 5 
antibody-positive dermatomyositis complicated by rapidly progressing interstitial pulmonary disease: Two 
case reports [J]. World J Clin Cases, 2023, 11(22): 5351-7. 
12.  SU C F, LIAO H T, TSAI C Y. Tocilizumab and rituximab for anti-MDA-5 positive amyopathic 
dermatomyositis complicated with macrophage activation syndrome and progressive fibrosing interstitial 
lung disease [J]. Scand J Rheumatol, 2022, 51(2): 166-8. 
13.  Chinese Expert Consensus on Diagnosis and Treatment of Adult Dermatomyositis (2022) [J]. Chinese 

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Journal of Dermatology, 2022, 55(11): 939-948.