Such rare autoimmune diseases are a little difficult to treat clinically!

*It is only for medical professionals to read for reference.
Although refractory myositis is difficult to treat, there is a chance to cure it! Difficulty in climbing stairs, laborious lifting, muscle aches and weakness.
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These "small problems" did not attract attention at the beginning.
Many patients thought it was caused by overwork, and rested for a period of time to get better
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However, as the disease continues to progress, muscle weakness gradually evolves into muscle atrophy, and the symptoms may no longer be confined to muscle tissue, and a series of extramuscular features appear
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Why is this? Idiopathic inflammatory myopathy (IIMs) is a group of chronic autoimmune diseases that mainly affect the proximal muscles, usually including polymyositis (PM), dermatomyositis (DM), immune necrotizing myopathy (NAM) ), inclusion body myositis (IBM), etc.
The common feature is that chronic inflammation of skeletal muscle leads to muscle weakness-the non-specific characteristics mentioned above
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In addition, they have different clinicopathological characteristics and strong heterogeneity
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In this issue, we will learn about the exploration road of IIMs in the future
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There are few studies and difficult treatments.
IIMs are a group of relatively rare diseases.
The incidence and prevalence reported by different studies vary greatly, but they are all lower than other common rheumatic diseases (such as rheumatoid arthritis, systemic erythema).
Lupus), and there is no relevant epidemiological survey data in China [1]
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The ever-changing clinical characteristics of IIMs make it extremely difficult to evaluate the disease state and clinically related improvements
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Therefore, few large-scale treatment research results have been published, and there are no standard treatment guidelines to guide clinical decision-making [2]
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Standard therapy for IIMs usually includes high-dose glucocorticoids and immunosuppressive agents (Figure 1)
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Intravenous immunoglobulin (IVIG) can be used alone as a first-line, second-line or third-line treatment, and can also be used in combination with any drugs according to the clinical manifestations or refractory of the disease [2]
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The main purpose of clinical treatment is to restore the patient's muscle strength, relieve/eliminate inflammation, and prevent damage to other organs
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Figure 1: Commonly used therapeutic drugs for IIMs [2] (MTX: methotrexate; AZA: azathioprine; MMF: mycophenolate mofetil; TAC: tacrolimus; CsA: cyclosporine; RTX: rituximab Monoclonal antibody; CTX: cyclophosphamide) but not all patients with IIMs can benefit from standard treatment.
The response of different patients to treatment varies greatly.
A considerable number of patients do not respond well to this, and symptoms persist in muscles, skin, and lungs.
Department, leading to worsening of the condition and becoming refractory IIMs[3]
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The safety of medication has also become a major challenge-the long-term use of glucocorticoids has serious side effects and cannot be overly dependent on this
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Speeding up the exploration of disease mechanisms and looking for potential therapeutic targets for targeted agents targeting the potential pathogenic pathways of IIMs may be an effective way to overcome the current difficulties in the treatment of IIMs
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With the development of various studies, a variety of potential biological therapeutic targets and drugs that can be used in clinical trials have been identified (Figure 2) [2]
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Figure 2: Immune-related potential therapeutic targets for myositis [2] B cell targeted therapy: Rituximab (RTX) is the main mechanism of action to promote B cell depletion
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So far, only one randomized controlled trial (RIM) has studied the efficacy of RTX in the treatment of IIMs [4].
Although the study did not reach the primary and secondary endpoints, 83% of patients with refractory myositis reached the international myositis assessment And the initial definition of myositis improvement (DOI) by the Clinical Research Group (IMACS) indicates that the role of B cell depletion therapy in IIMs is still worthy of further study [5]
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Cytokine targeted therapy: Among the many inflammatory cytokines, the most well-known is tumor necrosis factor-α (TNF-α)
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Regarding TNF-α inhibitors, currently only three drugs (infliximab, adalimumab, etanercept) have IIMs-related research reports, but the results are conflicting, and the efficacy is still uncertain
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And due to the small number of studies and the limited sample size, it is difficult to evaluate their safety in the treatment of IIMs [5]
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The efficacy of other targeted agents, such as IL-6 inhibitors and JAK inhibitors, is still underway [6-9]
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With the in-depth development of these studies, we have made strides towards the goal of overcoming refractory IIMs
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What is the progress of research on the efficacy of this potential new therapeutic drug? For a long time, IIMs such as PM and DM have been considered to be T cell-mediated autoimmune diseases.
In the infiltration of inflammatory cells in the muscle tissue of patients, there are a variety of abnormal T cell subgroups.
Therefore, T cells are considered to be specific for IIMs.
Sexual treatment targets (Figure 3) [10]
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Figure 3: The adaptive immune mechanism of myositis muscle injury [11] Abatacept is a T cell costimulatory signal regulator that can inhibit the activation of T cells
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A randomized, phase IIb, open-label, delayed treatment study explored the efficacy of abatacept in the treatment of refractory DM/PM in adults
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Twenty adult patients with refractory DM/PM were randomly assigned to the active treatment group (group A) and the delayed treatment group (group B).
After 6 months of treatment, 8 patients (42%) achieved DOI, and muscle function of all patients was significantly improved And the improvement in muscle function of patients in the active treatment group was more significant than that in the delayed treatment group (Figure 4), during which no serious adverse events occurred [12]
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Figure 4: Changes in the total improvement score of the two groups of patients with treatment time.
In addition, multiple cases have reported the effectiveness and safety of abatacept in the treatment of refractory PM/DM (Table 1)
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Data show that abatacept has the effects of improving muscle strength and reducing hormone consumption in treatment, and infection events will also be reduced [13-17]
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Table 1: Abatacept treatment of myositis cases [13-17] LDH: lactate dehydrogenase; ALD: aldosterone; SRP: signal recognition particles; CMAS: Child Myositis Assessment Scale, with a total score of 52; CHAQ: children Health assessment questionnaire, with a total score of 3 points
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More and more research evidences indicate that targeted agents may be the "good medicine" for the treatment of refractory IIMs, but limited by fewer experimental data, the results are unclear
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In order to further clarify the efficacy of abatacept in IIMs, more clinical studies are being prepared or underway (Table 2, data from ClinicalTrials.
gov) [18]
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We look forward to the arrival of these results to support the clinical application of new drugs
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Table 2: Summary of ongoing research on abatacept in the treatment of myositis: The choice of drugs for refractory IIMs is a major difficulty in its treatment.
The exploration of disease mechanisms and the development of targeted drugs are the keys to overcome difficulties and achieve breakthroughs
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The preliminary research results of abatacept and small sample case reports indicate that it has a good effect on refractory IIMs and is expected to be developed for clinical treatment of the disease
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At present, more in-depth research is still in progress, let us look forward to it together
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[18] https://clinicaltrials.
gov/ct2/home*This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position
.