Retirement does not fade, how to let the elderly RA patients get rid of the disease and return to the art hall?

*For medical professionals only

Mo Dao Sang Yu is late, and the sky is still full of Xia
.

With the improvement of living standards and medical conditions, the average life expectancy of human beings is getting longer and longer, and the population is seriously
aging.
The elderly are an important group in society and play a key role
in the stability and harmony of society.
Paying attention to the health of the elderly and promoting the social participation of the elderly is the only way
for us to actively cope with the aging of the population.

Rheumatoid arthritis (RA) is a disease that is extremely harmful to the elderly, and symptoms such as joint swelling and deformity will lead to a decrease in the quality of life, limited mobility and dysfunction of the elderly, which is not conducive to their self-care and social participation
.
In addition, elderly patients with RA can also be accompanied by a variety of comorbidities or underlying diseases, which makes treatment and management difficult
.
In this issue, Dr.
Cao Heng of the First Affiliated Hospital of Zhejiang University School of Medicine will share with us a case of clinical application of a new small molecule drug Eramod for the treatment of geriatric onset RA, welcome to discuss and learn
together.

Classic cases take a sneak peek

▎Basic information: Female, 74 years old, retired literary and art worker
.

▎Complaint: swelling and pain in multiple joints throughout the body for 3 years
.

▎Current medical history: 3 years ago, the patient had generalized polyarticular swelling and pain without obvious causes, mainly bilateral proximal fingers, wrists, elbows, knee joint swelling and pain, mild degree, continuous non-alleviation, no fever rash, no facial erythema, no dry mouth and dry eyes, and the local hospital diagnosed "osteoarthritis", for acupuncture and traditional Chinese medicine treatment
.
Over the past 3 years, patients complained of swelling and pain in the joints gradually aggravated, the digital pain score (NRS) was about 3-4 points, accompanied by morning stiffness (lasting about 30 minutes), and there was discomfort such as limited walking, cold and fever, no fatigue and weight loss, and the outpatient clinic proposed to be admitted to the hospital
for "arthritis".

▎ Past history: history of hypertension for more than 10 years, history of type 2 diabetes for more than
2 years.

▎Physical examination:
clear consciousness, mental fitness, no yellowing of the skin sclera of the whole body, superficial lymph nodes are not enlarged, neck is soft and no resistance, thyroid is not enlarged, breathing is stable, breathing in both lungs is coarse, and there is no obvious dry and wet rally
.
The heart rhythm is uniform, the valve area has not heard pathological murmurs, the abdomen is soft, the whole abdomen is not tender, the liver and spleen are not under the ribs, the masses are not reached, and the bowel sounds are 4 times / minute
.

Spindle swelling of the proximal interphalangeal joint, swelling of the wrists and elbows with mild tenderness, NRS 3 points, swelling and tenderness of both knees, limited movement of
the left knee.
The dorsal artery beats of both lower extremities are palpable, there is no abnormal depth of sensation, and there is edema
of the inferior lower extremities.

▎Laboratory test: The examination results are shown in Table 1, and there are no abnormalities
in antistreptolysin O (ASO), HLA-B27, thyroid function, immunoglobulin, complement, myocardial enzyme spectroscopy, and bone metabolism.

Table 1: Admission laboratory test results ▎ Imaging tests:

• Ultrasound of both wrists: manifestations
  of inflammatory arthropathy.
  Swelling of the soft tissues of both wrists, synovial hyperplasia (moderate) with inflammatory changes (energy Doppler flow signal level 2), local bone destruction
  .
  
• MRI flat sweep of the right elbow joint: 1.
  Multiple myeloid edema of the lower part of the right humerus, ulna, and proximal radius are considered
  .
  2.
  Effusion in the right elbow; With swelling of surrounding soft tissues, thickening of the synovium, and edema
  of the subcutaneous tissue.
  
• Electromyography of extremities: sensory and motor nerve conduction velocities are normal
  .
  
• Bone density: L2 lumbar spine T value -3.
  6, osteoporosis
  .
  
• Orthogonal footage of both hands (Figure 1): osteoporosis of the left and right hands, degeneration of the wrist joints on both sides, and arthritis changes
  .
  Improved Sharp Score (mTSS): 97 points
  .
  

 

Figure 1: Positive oblique piece of the hands

• CT of the lungs (Figure 2): bronchial lesions of both lungs, small nodules in the left upper lung, proliferative foci considered
  .
  Interstitial changes
  in the lungs twice.
  

 

Figure 2: HRCT ▎ Assessment of lung HRCT
▎ Disease Activity DAS28-ESR: 6.
11 (High Disease Activity); Health Questionnaire Disability Index (HAQ-DI): 1.
95 (Very Difficult in Daily Life Self-care).


▎Diagnosis: rheumatoid arthritis, osteoporosis, interstitial lung disease, type 2 diabetes, hypertension, mild anemia
.

▎Treatment process:

• Treatment option 1: celecoxib 200 mg QD + methotrexate 10 mg QW + hydroxychloroquine 200 mg BID + triptolide 10 mg TID
  .
  

After 3 weeks of treatment, the patient had some relief of joint swelling and pain and decreased leukocytes, but RA remained in moderate disease activity (DAS28-ESR: 4.
67, HAQ-DI: 1.
55).

In addition, because the patient has interstitial lung disease, the consideration of methotrexate may aggravate the condition, and the treatment plan is adjusted as follows
.

• Treatment option 2: Eramoud 25 mg BID + hydroxychloroquine 200 mg BID + triptolide 10 mg TID
  .
  

After 2 weeks of treatment, the patient's joint swelling and pain continued to relieve, white blood cells returned to normal, and disease activity continued to improve
.

Laboratory tests are performed after 5 weeks of treatment: blood count, inflammatory indicators, and RF return to normal (Figure 3
).
The specific results are shown in Table 2
.
The DAS28-ESR score dropped to 3.
13 and the HAQ-DI score was 1.
25
.

Table 2: Laboratory test results
for 5 weeks of admission Figure 3: ESR levels change during treatment

Diagnosis and treatment thinking

RA is one of the main causes of labor loss and disability in our population^[1].

Depending on the age of onset, RA can be divided into RA (EORA) with geriatric onset (i.
e.
, onset at the age of > 60) and RA (YORA)
with onset in young adults.
EORA has its own characteristics in terms of clinical manifestations, diagnosis and treatment, and the choice of treatment plan, disease control and prognosis improvement deserve widespread attention and attention in clinical practice
.

EORA tends to be acutely onset with a high degree of activity, more common systemic symptoms[^1], high levels of inflammation, and more likely to be associated with pleural effusion, interstitial lung disease, venous thrombosis, hypertension, diabetes, cerebrovascular disease, coronary heart disease, peripheral atherosclerosis, cataracts, and other diseases^[2].

Compared with patients with YORA, quality of life is more degraded and the prognosis is poor[^3].

Studies have shown that a high baseline disease activity score, concomitant interstitial lung disease, and pulmonary hypertension are independent risk factors for disease remission in EORA patients ^[3
].
As a result, patients with EORA need more aggressive intervention regimens, taking into account the treatment of comorbidities to improve their survival and quality of
life.

In addition, due to the decline of bodily functions and the presence of comorbidities, drug resistance in older patients tends to be poor, adverse reactions increase, drug metabolism changes, drug therapy is slow to achieve results, the treatment experience is relatively poor, and compliance is reduced ^[4].

Based on the above characteristics, reasonable selection of therapeutic drugs to reduce adverse reactions, improve treatment compliance, and achieve both efficacy and safety is an important strategy for the clinical treatment of elderly patients with RA
.

Commonly used drugs for RA treatment include glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), traditional synthetic disease-improving antirheumatic drugs (csDMARD), and targeted drugs (b/tsDMARD) and proprietary Chinese medicines, which vary
in efficacy and safety risks in elderly patients with RA 。 Eramod is a novel small molecule DMARD that has been shown in various clinical studies, whether single-agent or combination, to significantly alleviate clinical symptoms, reduce disease activity, improve bone metabolism in elderly patients with RA ^[5-10].

In addition, the safety of Eramod is also within an acceptable range, and adverse reactions such as liver enzyme abnormalities are mild and transient, mainly appearing at the beginning of treatment, after which they gradually decrease or resolve spontaneously
.

In this case, the patient with RA began to develop in old age, with polyarticular swelling and pain, difficulty walking, and repeated dry cough
.
The patient is a retired literary and artistic worker, and his pursuit of his own quality of life, especially spiritual life, is high
.
After retirement, patients hope to continue to participate in colorful cultural activities in the art troupe and enrich their later life
.
However, due to RA, the patient's movement is limited, he cannot complete the rehearsal performance, and he needs to relieve symptoms and improve his condition
through treatment.
In addition to RA, patients also have osteoporosis and interstitial lung disease, and there are certain requirements
for bone protection and improvement of lung function during treatment.
Clinical studies have shown that Eramod can produce a good therapeutic effect on pulmonary fibrosis by influencing inflammatory infiltration and collagen deposition, and may have some effect on the stabilization or improvement of interstitial lung disease ^[11-12].

Therefore, for this patient, Eramod has both significant efficacy on RA, bone protection and good safety, and also plays a positive role
in the management of comorbidities.

After receiving treatment with Eramod combined with hydroxychloroquine and triptolide, the inflammatory indicators were effectively controlled, the joint symptoms continued to relieve, the disease activity was significantly reduced, and no obvious adverse reactions occurred
during the treatment.
This shows that Eramod in combination with other DMARDs has good efficacy and safety in the treatment of EORA patients, and has multiple application advantages
.

Expert profile
Cao Heng

• Deputy Director of the Department of Rheumatology and Immunology, First Hospital of Zhejiang University, Doctor of Medicine, Deputy Chief Physician, Master Supervisor

• Vice President and Director General of Rheumatology and Immunology Branch of Zhejiang Medical Doctor Association

• Standing Committee Member of Rheumatology Branch of Zhejiang Medical Association

• Young member of the Rheumatology Branch of the Chinese Medical Association

• Young member of the Rheumatology and Immunology Branch of the Chinese Medical Doctor Association

• Member of the Imaging Group of the Rheumatology and Immunology Branch of the Chinese Medical Doctor Association

• He is a member of the Rare Diseases Branch of Zhejiang Medical Association

• Young member of the Internal Medicine Branch of Zhejiang Medical Association

• Standing Committee Member of the Rheumatology Branch of the Association of Mathematical Medicine

• Visiting scholar at the University Hospital of Grenoble, France

References:

[1] LI Zhanguo,WANG Hui.
Progress in the diagnosis and treatment of rheumatoid arthritis in the elderly[J].
Practical Geriatrics, 2008, 22(1): 7-11.

[ZHANG JANFENG,YE Xiuling,DUAN Meng,et al.
Comparison of clinical features of rheumatoid arthritis in the elderly and young adults[J].
Chinese Medical Journal, 2020, 100(47): 3788-3792.

[3]Ke Y, Dai X, Xu D, et al.
Features and Outcomes of Elderly Rheumatoid Arthritis: Does the Age of Onset Matter? A Comparative Study From a Single Center in China[J].
Rheumatol Ther.
2021, 8(1): 243-254.

[ZHANG Qian,WANG Li,CHEN Peng,et al.
Effect of integrated nursing intervention on elderly patients with rheumatoid arthritis[J].
Yishou Baodian, 2021, 7: 75-77.

Zhu Hui, Song Liping, Liu Sha, et al.
Study on the efficacy and safety of Eramod in the treatment of rheumatoid arthritis in the elderly[J].
Journal of Chinese and Foreign Medicine, 2020 (20): 4-6.

Meng Yan, Li Mingyuan, Luo Demei, et al.
Clinical study of Eramod tablets combined with methotrexate tablets in the treatment of rheumatoid arthritis in the elderly[J].
Chinese Journal of Clinical Pharmacology, 2017, 33(12): 1098-1101.

Li Huiying.
Efficacy of Eramod on rheumatoid arthritis in the elderly and its bone metabolism analysis[J].
Chinese and Foreign Medical Journal, 2020, 20: 77-79.

[8]Mizutani S, Kodera H, Sato Y, et al.
Clinical effectiveness of iguratimod based on real-world data of patients with rheumatoid arthritis[J].
Clin Rheumatol.
2021, 40(1):123-132.

[9]Hara M, Ishiguro N, Katayama K, et al.
Iguratimod-Clinical Study Group.
Safety and efficacy of combination therapy of iguratimod with methotrexate for patients with active rheumatoid arthritis with an inadequate response to methotrexate: an open-label extension of a randomized, double-blind, placebo-controlled trial[J].
Mod Rheumatol.
2014, 24(3):410-8.

Dai Lu, Song Xinli, Qiu Xiaoming, et al.
Effect of Eramod combined with leflunomide in the treatment of moderate and severe elderly active rheumatoid arthritis[J].
JOURNAL OF PRACTICAL CLINICAL MEDICINE, 2019, 23(3): 73-77.

[11]Shu P, Shao SQ, Cai XN, et al.
Iguratimod attenuates general disease activity and improves lung function in rheumatoid arthritis-associated interstitial lung disease patients[J].
Eur Rev Med Pharmacol Sci, 2021, 25(14): 4687-4692.

[12]Han Q, Zheng Z, Liang Q, et al.
Iguratimod reduces B-cell secretion of immunoglobulin to play a protective role in interstitial lung disease[J].
Int Immunopharmacol, 2021, 97: 107596.
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