A Study on the Clinical Efficacy and Safety of Telitacicept Combined With Baricitinib in the Treatment of Difficult-to-Treat Rheumatoid Arthritis (D2T RA)
Conditions: Telitacicept, Treatment Compliance, Rheumatoid Arthritis
Sponsor: Zhejiang Provincial People's Hospital

Research Program
（Version number: 01
Version date: 2025-12-10）
Project name: Clinical efficacy and safety of real-world patients with refractory
rheumatoid arthritis (D2TRA) treated with Telitacicept in combination with
Baricitinib
Bidder: Zhejiang Provincial People's Hospital
Department: Rheumatology and Immunology
Principal Investigator: Zhenhua Ying
Investigator's statement and protocol signature page
As the principal person in charge of this research project, I will follow the Ethical
Review of Biomedical Research Involving Human Beings (2016) of the Ministry of
Health, the Declaration of Helsinki (2013) of the WMA and the International Ethical
Guidelines for Human Biomedical Research (2002) of the CIOMS and the ethical
principles of the GCP, using the protocol approved by the ethics committee under the
guidance of the quality management specifications for drug clinical trials, and
conducting the study in accordance with the requirements of this protocol to ensure the
scientific validity of the study and to protect the health and rights of the subjects.
Name：________________
Signature：________________
Date：________________

Program Summary
Program Title
Clinical efficacy and safety of real-world patients with
refractory rheumatoid arthritis (D2TRA) treated with
baricitinib in combination with tofacitinib
Version
number/version date
01/2025-12-10
Sponsors and
Participating Units
Zhejiang Provincial People's Hospital
Principal
Investigator
Nature of Research
Clinical Studies
Purpose of the study To observe the clinical efficacy and safety of Telitacicept
combined with Baricitinib in the treatment of D2TRA
patients
Sample size
20
Research Subjects
Patients with refractory rheumatoid arthritis
Research
Methodology
A real-world observational study. Prospectively included
30 patients with Difficult-to-Treat Rheumatoid Arthritis
(D2T RA) who were treated at the outpatient and
inpatient departments of Zhejiang Provincial People's
Hospital from January 2026 to January 2028. These
patients had shown an inadequate response to traditional
disease-modifying antirheumatic drugs and had failed
treatment with two or more biologic/targeted disease-
modifying antirheumatic drugs, requiring treatment with
Telitacicept combined with Baricitinib. They were
enrolled as the observation group. Medications were
prescribed according to the maximum reimbursement
duration (4 weeks) under medical insurance. Changes in
laboratory tests, tender joint count (28 joints), swollen
joint count (28 joints), and DAS28 scores were observed
in the Telitacicept combined with Baricitinib treatment
group. Self-comparisons were conducted at baseline, 4,
8, 12, 16, 20, and 24 weeks. Changes in joint ultrasound
findings and adverse reactions were also monitored.
Inclusion Criteria
1.Age 18-85 years;​
​
2.Diagnosed with refractory rheumatoid arthritis
according to the 2021 EULAR (European Alliance of
Associations for Rheumatology) diagnostic criteria;​
3.The traditional disease-improving rheumatic drug
treatment is ineffective, and the use of two or more
biological/targeted disease-improving anti-rheumatic
drugs is ineffective, and telitacicept combined with

tofacitinib is required treated patients;
4.Voluntarily provided written informed consent.​
Exclusion Criteria
1.Exclusion of patients with severe diseases of major
organs (e.g., heart, liver, or lungs);​
​
2.Patients with malignancies, hematological disorders, or
other autoimmune diseases (excluding rheumatoid
arthritis);​
​
3.History of allergy/hypersensitivity to the study
medications (Telitacicept or Tofacitinib);​
​
4.Active tuberculosis or active infectious diseases
requiring systemic treatment;​
​
5.Pregnancy, lactation, or refusal to use contraception
during the study;​
​
6.Failure to complete the prescribed Telitacicept +
Tofacitinib regimen due to:​
​
Non-adherence or Severe
adverse reactions ；
7.Other conditions contraindicating participation per
investigator judgment.​
​
Research Progress
Plan
2026.1-2028.1
Statistical analysis
methods
SPSS software was used for statistical analysis.
Normality tests were performed using SPSS software
was used for statistical analysis. Normality tests were
performed using the Kolmogorov-Smirnov test, and
measures conforming to a normal distribution were
expressed as mean ± standard deviation (x ± s), and
comparisons between groups were made using the two
independent samples t-test; measures not conforming to a
normal distribution were described by median and
interquartile spacing, i.e., median (25th percentile, 75th
percentile) [M( P25,P75)], and comparisons between
groups were made using the Mann-Whitney U anecdotal
test The difference between groups was considered
statistically significant at P < 0.05. The data were
analyzed by the chi-square test or Fisher's exact
probability method.
Form of publication
of research results
Published 1-2 papers

1. Purpose of the study
(1)To observe the effect of Telitacicept combined with Baricitinib on the clinical
efficacy of D2T RA patients
(2)To observe the safety of Telitacicept combined with Baricitinib in the treatment of
D2T RA patients
2. Background of the study
Rheumatoid arthritis (RA) is a common systemic inflammatory autoimmune
disease characterized by synovitis and bone destruction. Epidemiological data indicate
a global RA prevalence of 0.5%-1%, with approximately 0.42% in China, totaling
over 5 million affected individuals. RA is also one of the most disabling diseases in
China, with a disability rate as high as 61.3%. The pathogenesis of RA remains
unclear, but its fundamental pathology involves synovitis, pannus formation, and
progressive destruction of articular cartilage and bone, ultimately leading to joint
deformity and functional loss. RA is associated with comorbidities such as pulmonary
diseases, cardiovascular disorders, malignancies, and depression. Beyond impairing
physical function, quality of life, and social participation, RA imposes substantial
economic burdens on patients, families, and society. Early detection, diagnosis, and
treatment are critical for optimizing therapeutic outcomes.
Current RA management relies primarily on pharmacotherapy. The 2018
Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis classify
therapeutic
agents
into
four
categories:
nonsteroidal
anti-inflammatory
drugs
(NSAIDs), disease-modifying antirheumatic drugs (DMARDs), glucocorticoids (GCs),
and herbal medications. While these drugs control symptoms and slow disease
progression, they cannot fully halt structural damage. Over the past three decades,
breakthroughs have been achieved with biological DMARDs (bDMARDs, e.g., TNF-α
inhibitors, IL-6 inhibitors, B-cell-depleting antibodies, and co-stimulation molecule
inhibitors) and targeted synthetic DMARDs (tsDMARDs, e.g., pan-JAK and JAK1/2
inhibitors).

Despite advancements in drug development and the clinical implementation of
treat-to-target strategies, approximately 5% – 20% of RA patients exhibit persistent
disease activity and are classified as having difficult-to-treat RA (D2T RA). In 2021,
the European Alliance of Associations for Rheumatology (EULAR) established three
diagnostic criteria for D2T RA:(1) failure of csDMARDs after treatment according to
the EULAR recommendations (unless there is a contraindication) after failure of ≥
2b/tsDMARDs (with a different mechanism of action); (2) presence of at least one of
the following: at least moderate disease activity; signs and/or symptoms suggestive of
active disease; inability to taper glucocorticoid therapy; rapid imaging progression;
RA symptoms leading to decreased quality of life; (3) rheumatologists and/or patients
who believe that signs and/or symptoms of treatment is problematic.
D2T RA patients often exhibit poor adherence, lower socioeconomic status, and
comorbidities such as fibromyalgia, osteoarthritis, and pain syndromes. These
individuals experience suboptimal clinical responses, higher rates of joint deformity,
and greater disease-related economic burdens compared to typical RA patients,
making D2T RA a critical unmet need in rheumatology.
Exploring novel therapeutic strategies for D2T RA has become a priority. While
RA pathogenesis remains incompletely understood, it is recognized as an immune-
pathological process triggered by environmental factors in genetically predisposed
individuals, with immune dysregulation playing a central role. Emerging evidence
highlights abnormal activation of autoreactive B cells — which breach immune
tolerance and produce autoantibodies (key RA biomarkers) — as pivotal in RA
progression. B-cell-targeted therapies (e.g., rituximab) are widely used, yet single-
target approaches face limitations due to the complexity of immune regulatory
networks. Consequently, multi-target strategies modulating multiple pathways have
gained traction, offering enhanced efficacy and reduced adverse effects.
China's first domestically developed dual-target biologic drug, Telitacicept, is a
TACI-Fc fusion protein composed of the extracellular domain of the human
transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI)

receptor and the Fc domain of human immunoglobulin G (IgG). This novel structure
enables dual-target inhibition of two cytokines critical for B-lymphocyte development:
B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL). By
suppressing B-cell-mediated autoimmune responses, Telitacicept effectively treats
autoimmune diseases. Clinical studies have demonstrated the safety and tolerability of
dual BLyS/APRIL inhibition in healthy populations. Approved in 2021 for systemic
lupus erythematosus (SLE), Telitacicept has shown robust efficacy and safety in SLE
management, with infections being the most common adverse event. Phase III trials
for IgA nephropathy (IgAN), myasthenia gravis (MG), and neuromyelitis optica
spectrum
disorder
(NMOSD)
are
ongoing.
Notably,
Telitacicept
reduces
glucocorticoid dependence and improves clinical stability in steroid-intolerant
autoimmune disease (AID) patients, demonstrating promising potential for rheumatoid
arthritis (RA) treatment.
In the quest for optimized difficult-to-treat RA (D2T RA) therapies, targeting
alternative pathways is pivotal. The 2021 ACR guidelines recommend switching to
JAK inhibitors after initial treatment failure. JAK kinases, non-receptor tyrosine
kinases associated with cytokine receptors, activate the JAK-STAT signaling pathway-
a key driver of RA pathogenesis. JAK inhibitors, as targeted synthetic DMARDs
(tsDMARDs), competitively bind to ATP sites on JAK1/JAK2/JAK3, blocking
phosphorylation and downstream inflammatory cascades.
Baricitinib, a selective JAK1/JAK2 inhibitor, belongs to the class of tsDMARDs.
It works by blocking the JAK-STAT signaling pathway, inhibiting the intracellular
transmission of various pro-inflammatory cytokines (such as IL-6, IFN- γ , IL-23),
thereby alleviating inflammatory responses and joint damage in rheumatoid arthritis
(RA). Additionally, baricitinib can modulate immune cell functions, for example, by
inhibiting the activation of Th17 cells (associated with autoimmune responses) and
promoting the differentiation of regulatory T cells, which helps restore immune
balance and improve clinical symptoms in patients with difficult-to-treat RA.
Furthermore, safety study results indicate that the most commonly reported adverse

events for this drug include infections, changes in laboratory parameters, and some
gastrointestinal symptoms. Other serious adverse events, such as cardiovascular events,
thromboembolism, serious infections, interstitial lung disease, and malignancies, are
relatively rarely reported.
The Phase III trial of Telitacicept for RA, completed in 2023 and presented at the
ACR Annual Meeting, met all primary endpoints with favorable safety. Telitacicept's
dual BLyS/APRIL inhibition reduces autoantibody production by targeting B cells,
complementing tofacitinib's suppression of T-cell-driven cytokines (e.g., IL-6, IL-17)
via JAK-STAT blockade. This dual-pathway strategy addresses both B- and T-cell
dysregulation
in
RA,
mirroring
successful
multi-target
approaches
in
other
autoimmune diseases (e.g., rituximab-abatacept combinations in refractory RA, albeit
with infection risks).
The 2022 EULAR guidelines emphasize stratified combination therapy for RA.
For patients with poor prognostic factors (autoantibody positivity, high disease activity,
early erosions, or dual csDMARD failure), adding bDMARDs/tsDMARDs to
csDMARDs
is
recommended
after
3-6
months
of
inadequate
response
to
methotrexate/glucocorticoids. Subsequent treatment failure warrants switching to
alternative b/tsDMARDs. Abbasi et al. propose that combining biologics (or
biosimilars) with DMARDs enhances outcomes, highlighting the therapeutic rationale
for Telitacicept-tofacitinib synergy. Given their distinct mechanisms-Telitacicept’s B-
cell modulation and tofacitinib’s cytokine inhibition-this combination may offer new
hope for D2T RA patients, leveraging targeted efficacy, safety, and cost-effectiveness.
3. Test basis
(1)Pre-study animal experiments and literature base
Clinical Trial：Lv J, Liu L, Hao C,et al. Randomized Phase 2 Trial of Telitacicept in
Patients With IgA Nephropathy With Persistent Proteinuria. Kidney Int Rep. 2022 Dec
29;8(3):499-506. doi: 10.1016/j.ekir.2022.12.014.
Cai S, Hu Z, Chen Y,et al. BLyS/APRIL dual inhibition for IgG4-RD: a prospective
single-arm clinical trial of telitacicept. Ann Rheum Dis. 2023 Jun;82(6):881-883. doi:

10.1136/ard-2022-223529.
Wu D, Li J, Xu D, et al. Telitacicept in patients with active systemic lupus
erythematosus: results of a phase 2b, randomised, double-blind, placebo-controlled
trial. Ann Rheum Dis. 2024 Mar 12;83(4):475-487. doi: 10.1136/ard-2023-224854.
(2)Subject selection basis Patients diagnosed with refractory rheumatoid arthritis who
meet the 2021 European League Against Rheumatism (EULAR) diagnostic criteria for
refractory rheumatoid arthritis
4. Resear ch Content
(1) Test population: patients with refractory rheumatoid arthritis
(2) Sample size: 30 D2TRA patients
(3) Specific study Content:A prospective cohort of 30 patients with Difficult-to-Treat
Rheumatoid Arthritis (D2T RA) was enrolled as the observation group. These patients,
attending the outpatient and inpatient departments of Zhejiang Provincial People's
Hospital between January 2026 and January 2028, had shown an inadequate response
to conventional disease-modifying antirheumatic drugs and had also failed treatment
with two or more biologic/targeted disease-modifying antirheumatic drugs, thereby
requiring therapy with Telitacicept combined with Baricitinib. Medications were
prescribed according to the maximum reimbursement duration (4 weeks) stipulated by
medical insurance. Changes in laboratory parameters, tender joint count (28 joints),
swollen joint count (28 joints), and DAS28 scores were observed in the Telitacicept
combined with Baricitinib treatment group. Self-controlled comparisons were
performed at weeks 0, 4, 8, 12, 16, 20, and 24. Concurrently, changes in joint
ultrasound findings and adverse reactions were monitored.
5. Resear ch Methodology:
Enrollment criteria (diagnostic criteria, inclusion criteria, exclusion criteria)
(1) Diagnostic criteria
The diagnostic criteria for D2TRA refer to the definition criteria proposed by EULAR
2021：

1. Failure of ≥2b/tsDMARDs (with different mechanisms of action) after
failure of csDMARDs therapy (unless contraindicated) according to the
European Rheumatology Consortium recommended treatment.
2. Presence of ≥1 of the following signs indicative of active/progressive
disease.
a. At least moderate disease activity (based on validated composite
metrics including joint counts such as DAS28-ESR > 3.2 or CDAI > 10).
b. Signs (including acute phase reactants and imaging) and/or symptoms
(joint related or otherwise) suggestive of active disease.
b. Inability to taper glucocorticoid therapy (prednisone below 7.5 mg/day
or equivalent dose).
c. Rapid progression of imaging (with or without signs of active disease).
d. Good control of the disease according to the above criteria, but still
have RA symptoms that lead to a reduced quality of life.
3. Rheumatologists and/or patients who perceive signs and/or symptoms
as problematic in the treatment.
All three criteria need to be present in D2T RA.
b, Biological; CDAI, clinical disease activity index; cs, conventional synthesis;
DAS28-ESR, the disease activity score of 28 joints was evaluated by ESR; DMARD,
disease-modifying antirheumatic drug; mg, milligram; RA, rheumatoid arthritis; ts,
targeted synthetic.
* Unless restricted by access to treatment due to socioeconomic factors.
† If csDMARD treatment is contraindicated, failure of ≥2 b/tsDMARDs with
different mechanisms of action is sufficient.
‡ Rapid radiographic progression: change in van der Heijde-modified Sharp score ≥5
points at 1 year.
(2) Inclusion Criteria:
1.Age 18-85 years;​
​

2.Diagnosed with refractory rheumatoid arthritis according to the 2021 EULAR
(European Alliance of Associations for Rheumatology) diagnostic criteria;​
3.The traditional disease-improving rheumatic drug treatment is ineffective, and the
use of two or more biological/targeted disease-improving anti-rheumatic drugs is
ineffective, and telitacicept combined with tofacitinib is required treated patients;
4.Voluntarily provided written informed consent.​
(3) Exclusion Criteria:​
​
1.Exclusion of patients with severe diseases of major organs (e.g., heart, liver, or
lungs);​
​
2.Patients with malignancies, hematological disorders, or other autoimmune diseases
(excluding rheumatoid arthritis);​
​
3.History of allergy/hypersensitivity to the study medications (Telitacicept or
Tofacitinib);​
​
4.Active tuberculosis or active infectious diseases requiring systemic treatment;​
​
5.Pregnancy, lactation, or refusal to use contraception during the study;​
​
6.Failure to complete the prescribed Telitacicept + Tofacitinib regimen due to:Non-
adherence or Severe adverse reactions ；
7.Other conditions contraindicating participation per investigator judgment.​
​
6. Test procedure
1. Subject management
Subject recruitment method: Direct recruitment during the clinical care process
2. Informed consent process: Subjects voluntarily joined the study and voluntarily
signed the informed consent form.
7. Research Program
In this study, no additional interventions were applied to the subjects.​
A
prospective cohort of 30 patients with Difficult-to-Treat Rheumatoid Arthritis (D2T
RA) was enrolled as the observation group. These patients, attending the outpatient
and inpatient departments of Zhejiang Provincial People's Hospital between January

2026 and January 2028, had shown an inadequate response to conventional disease-
modifying antirheumatic drugs (DMARDs) and had also failed treatment with two or
more biologic/targeted DMARDs, thereby requiring therapy with a combination of
Telitacicept and Baricitinib. Telitacicept, manufactured by RemeGen Co., Ltd. (Yantai)
(National Medicine Permit No. S202110008), was administered at a dose of 160 mg
per injection subcutaneously once a week for six months. Baricitinib (Olumiant),
manufactured by Eli Lilly and Company (National Medicine Permit No. HJ20215001),
was administered orally at a dose of 2 mg once daily. Medications were prescribed
according to the maximum reimbursement duration (4 weeks) stipulated by medical
insurance. Changes in the following parameters were observed in patients before
treatment and at 4, 8, 12, 16, 20, and 24 weeks after treatment initiation: rheumatoid
factor, anti-cyclic citrullinated peptide antibody, immunoglobulins (IgG, IgA, IgM), C-
reactive protein, erythrocyte sedimentation rate, complete blood count, liver function,
renal function, tender joint count (28 joints), swollen joint count (28 joints), joint
ultrasound findings, DAS28-ESR score, and adverse reactions. Changes in laboratory
test indicators, tender joint count (28 joints), swollen joint count (28 joints), and
DAS28 scores in the Telitacicept combined with Baricitinib treatment group were
evaluated. Self-controlled comparisons were performed at weeks 0, 4, 8, 12, 16, 20,
and 24. Concurrently, changes in joint ultrasound findings and adverse reactions were
monitored to evaluate the clinical efficacy and safety of the combination therapy.
Clinical response was defined as follows: DAS28 ≤2.6 for clinical remission, 2.6 <
DAS28 ≤3.2 for low disease activity, 3.2 < DAS28 ≤5.1 for moderate disease activity,
and DAS28 > 5.1 for high disease activity.
8. Start and end of the experiment
2026.1-2028.1
9. Data Security and Monitoring Program
(This paragraph cannot be deleted, if not, fill in none. According to the requirements
of the Ministry of Health's Measures for Ethical Review of Biomedical Research
Involving Human Beings (2016), all research projects are required to have a data

security and monitoring plan, and this item is one of the criteria for the ethics
committee to review the project, please describe it specifically according to the
requirements.)
(1) Overview of data management methods
1.Data are traceable. All clinical trial data correspond to specific subjects and
investigators, and all modifications to the data are recorded in detail to create a series
of traceable verification traces.
2.Correctness of data. The correctness of data mainly includes the authenticity and
accuracy of data, all clinical trial data reflect the actual situation of the study truthfully
without any falsification, fiction and tampering; the accuracy is reflected in the
verifiable data sources, i.e. CRF, study records and entered data should be consistent
with the data obtained from the actual study.
3.Data completeness. Study data were collected completely for each subject, and
missing data due to special reasons were stated as to why they were missing.
4.Logical reasonableness of the data. To determine whether the data are logically
unreasonable from a clinical perspective.
5.Timeliness of data. The data are observed and completed in a timely manner at the
specified time points in the clinical trial.
(2) Adverse events and serious adverse events are reported and collected.
Reporting principles: 1. Report only adverse events related to the study drug. 2.
Complete the Spontaneous Adverse Event Report Form for all related adverse events
(serious and non-serious)
The following information should also be included to determine if the event is related,
possibly related, or potentially related to the drug. Determination of event-drug
relevance includes: 1. reasonable temporal sequence 2. dose-response relationship 3.
pharmacology 4. discontinuation of dosing and/or positive re-dosing.
Classification of the severity of drug-related adverse events：
Mild
The symptoms do not alter the patient's normal function.
Moderate
The symptoms result in some degree of functional

3) Medical safety measures
1. Collect information, focus on prevention. Supervise the department to report the
risk information of clinical medical research in a timely manner, so that the
information monitoring is in place and the risk prevention is effective.
2. Early warning, timely disposal. The department strengthens the monitoring of risks,
regularly monitors and inspects, and once problems are found, reports them to the
department head in a timely manner and takes decisive measures to control and
resolve the risks in a timely manner, prevent the expansion and spread of risks, and
minimize them.
3. We regularly assess risks and propose corrective measures to prevent them.
4.Before clinical research begins, the investigator must provide the subject with
information about the treatment and the subject's rights and obligations, so that the
subject fully understands and agrees to it, and signs an "informed consent" before the
clinical research experiment can begin. If one of the following situations occurs, the
emergency handling procedures should be started immediately to stop the scientific
clinical medical research and report to the Science and Education Section.
1. The research clinical medical research in the technical staff or key equipment,
facilities and other auxiliary conditions change, can not properly carry out clinical
research or may bring uncertain consequences.
2.The occurrence of serious adverse consequences directly related to the research
clinical medical study.
3.The ethical flaws in this research-based clinical medical study.
4.The medical quality and medical safety risks associated with this research-based
clinical medical
study.
impairment, but are not damaging, uncomfortable, or
embarrassing.
Severe
The symptoms are definitely detrimental to health, with
significant functional impairment or incapacity.

5. The clinical application of this research-based clinical medical study is inexact.
4) Communication with ethics committee and higher pharmacovigilance department
1.The research protocol needs to be developed and submitted to the Medical Ethics
Committee for approval prior to the start of the project.
2.The project research should be filed with the higher drug regulatory authorities in a
timely manner, and actively accept the guidance and supervision of the higher drug
regulatory authorities.
5）Internal analysis plan for data
1.Data Collection
Information about patients who met the enrollment criteria and data from laboratory-
related tests functional impairment or incapacity.were collected.
①Case collection form: includes basic information of enrolled patients, related
diseases, disease duration, treatment, and test data of related indicators for individual
data analysis.
②Summary table: includes the patient's disease and related index examination data for
overall data analysis.
2.Assessing the overall data situation
①Evaluate the integrity of each data source: timely recording of patient-related data to
ensure data integrity.
②Evaluate the accuracy and consistency of aggregated data: randomly check whether
the extracted data are consistent with those in the database to ensure data accuracy.
3.Data cleaning and collation
①Check for errors and outliers in the data that clearly defy common sense, and when
found, first check that the same patient metadata are the same, then check how this
data was collected, and finally how to assess whether it is an outlier from a technical
point of view, by using relevant statistical indicators and methods such as setting upper
and lower limits to deal with outliers.
②For special numbers, first mark "missing value", there is a perfect data dictionary to

query the actual situation of this field, if not need to promptly communicate to confirm
such issues
4.Data Collation
①Uniform formatting and naming rules for data
②Recoding of certain information to meet subsequent analysis needs
5.Data Visualization
Histograms, line graphs, scatter plots or heat maps are used to visualize the data of
patient-related indicators to show the data results and trends more clearly, so that the
study results can be presented more clearly.
6.Data Analysis
Complete the data and perform statistical analysis on those that meet the criteria
1 ）Frequency of data security and monitoring reports submitted to the ethics
committe
The research in this project is a low-risk study, so an annual review frequency is used.
Also, the principal investigator holds regular study meetings and notifies the ethics
committee if there are changes in the risk/benefit ratio of the study.
10.
Respect for ethical principles and related regulations
The study was conducted in strict compliance with international and domestic
standards and norms,including the Declaration of Helsinki ethical guidelines for
human medical research and the relevant Chinese clinical research study norms and
regulations. In the course of the study, if there is a need to revise this protocol, the
revised protocol must be submitted to the Ethics Committee again for approval before
implementation.
The Informed Consent Form for this study has been approved by the Medical
Ethics Committee. If the Informed Consent Form is amended in writing, it will be sent
to the Ethics Committee for approval to obtain the subject's consent again. Before the
start of the study, the investigator provides patients with detailed information about the
study, including the nature of the study, the purpose of the study, the possible benefits

and risks, and the rights and obligations of the patients. The patient is fully informed
and agrees, and signs the Informed Consent Form before the study can begin.
11.
Statistical analysis plan
SPSS software was used for statistical analysis. Normality tests were performed
using the Kolmogorov-Smirnov test, and measures conforming to a normal
distribution were expressed as mean ± standard deviation (x ± s), and comparisons
between groups were made using the two independent samples t-test; measures not
conforming to a normal distribution were described by median and interquartile
spacing,
i.e.,
median
(25th
percentile,
75th
percentile)
[M(
P25,P75)],
and
comparisons between groups were made using the Mann-Whitney U anecdotal test
Comparisons between groups were made using the Mann-Whitney U anecdotal sum
test; count data were expressed as percentages, and comparisons between groups were
analyzed using the chi-square test or Fisher's exact probability method, with
differences considered statistically significant at P < 0.05.
12.
Form of publication of research results
Published 1-2 papers
13.
Data Logging Form
Observed indicators
Week 0
Week 4
Week 8
Week
12
Week
16
Week
20
Week
24
Rheumatoid
factor
IU/ml
Anti-cyclic
citrullinated
peptide antibody
U/ml
Immunoglobulin
G
g/L
Immunoglobulin
A
g/L
Immunoglobulin
M
g/L
C-reactive
mg/L

protein
Blood
sedimentation
mm/h
Leukocytes
x109
/L
Blood platelets
x109
/L
Glutathione
aminotransferase
U/L
Glutathione
transaminase
U/L
Globulin
g/L
Creatinine
umol/
L
Glomerular
filtration rate
ml/mi
n
Glomerular
filtration rate
pcs
Swollen number
of 28 joints
pcs
DAS28-ESR
score
score
Ultrasound of joints
14.
Adverse reaction record form
No adverse events have
occurred
□yes
□no
Name of undesirable
events
Start date of occurrence
____Year_____month_____day
Dosing time and dosage
_____ year _____ month _____ day_____mg
Severity*
□Mild□Moderate□Severe
Whether to take measures
□yes
□no
Relationship to study
drugs
□Definitely related □Likely related □Possibly related
□Possibly
Unrelated □Definitely not related

Outcome of adverse
events that occurred
□Still exists
□Eased □No idea
Relief Date_____ year _____ month _____ day
Whether the patient
withdrew from the trial
because of the adverse
event
□yes
□no
Severity*: mild (no treatment, no discontinuation), moderate (discontinuation, no treatment),
severe(discontinuation, control treatment)