AS Excellent Case Sharing - Impaired Functions and Limited Activities, How to "Turn Things Around"?

*For medical professionals to read and refer to the sharing of outstanding cases of C pioneers - from clinical real cases, to discuss the first-line selection of AS biologics
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As the backbone of clinical diagnosis and treatment, young and middle-aged physicians shoulder heavy responsibilities
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"Pioneer C" focuses on the frontier progress of skin immunity and rheumatism immunity, and joins hands with big names in the field to bring together outstanding young and middle-aged physicians
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Young and middle-aged physicians incarnated as "Sherlock Holmes", with a professional and rigorous scientific attitude, they searched for the "true culprit" in "clues", "turned the tide" when the disease was "turbulent", and showed their brilliance and >
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The collision of the exchange of ideas ignites the spark of wisdom, and more excellent doctors will make their "C debut" on this stage! Ankylosing spondylitis (AS) is a relatively difficult disease faced by rheumatologists in clinical diagnosis and treatment - the large scale of the patient population, the characteristics of "long course of disease, late treatment, and high disability rate" [1] have made many newcomers of clinicians sighed: "I feel like I'm being 'squeezed' by AS diagnosis and treatment!" Let's take a look at what new ideas for diagnosis and treatment can be brought to us by the excellent cases in "Pioneers C"! The personnel are in place, and the "weapons" are upgraded again: usher in a new era of AS treatment! While improving the diagnosis and treatment capabilities of clinical medical staff, we also need to upgrade "weapons and equipment" in order to be ready to embark on a new journey of AS treatment
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IL-17 inhibitor is a new "weapon" in the current AS treatment field, and its application provides strong support for the realization of higher-level treatment goals
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 IL-17A is a key cytokine involved in the pathogenesis of AS, and is closely related to the pathological process of enthesitis, abnormal bone metabolism and osteophyte formation
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Inhibition of IL-17A is expected to inhibit the inflammatory response in the disease process, regulate abnormal bone metabolism and delay structural progression, and regulate the pathological process of AS at multiple levels [2-5]
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 Secukinumab is a fully human monoclonal antibody that specifically targets IL-17A.
Since its development and listing, it has accumulated a number of clinical research data and real-world application experience - for the use of non-steroidal anti-inflammatory drugs ( In AS patients with high disease activity after NSAIDs) treatment, secukinumab can significantly reduce disease activity, delay imaging progression, improve structural function and patient-reported outcomes, with rapid and stable efficacy [6-11] ; It has a good tolerance to common and special concern adverse events (such as tuberculosis, hepatitis B and other infection risks) [12]
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 At present, many doctors have used biological agents for AS patients in clinical practice, and the efficacy and safety of secukinumab have also been recognized by experts and doctors
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Among the cases collected by "Pioneer C", we have received many cases of the successful treatment of AS with secukinumab, and we will present two of them today
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 The cases introduced this time have certain common characteristics: 1) The patient was highly active at the time of consultation, and had already experienced pathological new bone formation or restricted movement, and it was imminent to delay the structural progress; Monoclonal antibodies are treated as first-line biologics
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So, what is the treatment effect of these two patients? For more details, see the analysis below
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In a dilemma? AS patients with epilepsy, this treatment "kills two birds with one stone"! (This case was provided by Dr.
Ding Shuang of the First Affiliated Hospital of China Medical University) Case details ▎Basic information of the patient: Male, 24 years old, was admitted to the hospital due to "five years of low back pain and aggravation for one month"
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▎History of present illness: 5 years ago, there was no obvious incentive for low back pain (obvious at night, which can be relieved after activity), and the diagnosis was not made in the local hospital, and no treatment was given; 3 years ago, the patient developed cervical stiffness and limited activity, Liaoning Hospital of Traditional Chinese Medicine was diagnosed with AS, and was given meloxicam for pain relief and traditional Chinese medicine treatment.
After taking it regularly for several months, the patient's symptoms were not significantly relieved, and the drug was discontinued on his own without regular review
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Because the pain persisted, the patient took oral analgesics to control it; 1 month ago, the patient felt that the pain was aggravated, and the conventional analgesics were not well controlled, so he was admitted to the ward for further diagnosis and treatment; the left hip and left knee joint pain at the time of illness, occasionally the knee joint Swelling and limited mobility; ▎Past history: when the patient was about 10 years old, there was a sudden disturbance of consciousness and foaming at the mouth, which resolved spontaneously after 1 minute, and was diagnosed as "epilepsy" in the local hospital; after that, symptoms occasionally occurred, and oral administration Sodium valproate sustained-release tablet treatment
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In the past two months, the attacks were more frequent than before
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 ▎Physical examination: slightly hunched back, limited cervical and lumbar spine movement, slightly swollen left knee joint, positive for tenderness; positive double "4" test, 20 cm from the ground and 8 cm from the ear wall
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 ▎Auxiliary tests: Laboratory tests: erythrocyte sedimentation rate (ESR) 32 mm/h, C-reactive protein (CRP) 46.
5 mg/L, HLA-B27 (+), IL-6: 7.
27 pg/mL, IL-17: 35.
69 pg/mL, other laboratory tests were basically normal; sacroiliac joint MRI: bilateral sacroiliac joint space was significantly narrowed, articular surfaces were irregular and blurred, local articular surfaces were unclear, and strips were seen under the sacral and ilium articular surfaces Blurred long T2 signal shadows
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Diagnosis: bilateral sacroiliitis, joint stiffness; Figure 1: MRI results of sacroiliac joints Cervical spine MRI and X-ray: cervical vertebra physiological curvature is straightened, slightly inverted arch, vertebral body bone hyperplasia and sharpening, The anterior edge of the C2-7 vertebral body is short and the T1 bright angle sign changes, the C2-3 intervertebral disc protrudes posteriorly, the anterior edge of the dural sac is compressed, and the C4-7 intervertebral disc is slightly kyphosis
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Diagnosis: C2-7 vertebral spondylitis, part of the prevertebral ligament calcification; Figure 2: Cervical spine MRI and X-ray examination results Lumbar spine MRI: lumbar curvature is straightened, bone hyperplasia can be seen at the edge of some vertebral bodies, T12-L2 vertebrae Anterior and superior border of the body with short T1 mixed signal
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Diagnosis: T12-L2 vertebral anterior and superior border spondylitis; Figure 3: Lumbar MRI results of femoral head CT: left acetabulum, subarticular surface of femoral head increased bone density, and small cystic degeneration can be seen on the left side The joint space is slightly narrow and the articular surface is slightly rough
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Diagnosis opinion: arthritis of the left hip; Figure 4: CT of the femoral head and B-ultrasound of the left knee joint: the synovial membrane of the joint is thickened by about 0.
19cm, and the power Doppler shows dot-like color blood flow (level 1 blood flow); Figure 5 : B-ultrasound brain-enhanced MRI of the left knee joint: scattered speckled and slightly long T2 signal shadows can be seen under the left parietal lobe and right frontal lobe, and the FLAIR sequence shows high signal, indicating small ischemic foci in the brain
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 Figure 6: Brain MRI + enhanced results ▎Admission diagnosis: ankylosing spondylitis, epilepsy
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▎Assessment of AS disease activity: AS disease activity score (ASDAS) 3.
8, Bath AS disease activity index (BASDAI) 4.
1, indicating high disease activity; Bath AS functional index (BASFI) 3, Bath AS measurement index (BASMI) 3 , suggesting that the patient has certain functional impairment and limited activity
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▎Therapeutic regimen: secukinumab 150 mg qw, sulfasalazine 1 g tid, sodium valproate sustained-release tablet 250 mg bid
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▎Efficacy evaluation: After 1 week of treatment, the patient's low back pain and joint swelling and pain were significantly relieved; after 4 weeks of treatment, the CRP and ESR levels were reduced to 4 mg/L and 3 mm/h respectively (upper Figure 7), ASDAS score After 24 weeks of treatment, the CRP and ESR levels were 5 mg/L and 5 mm/h, respectively (lower figure 7), the ASDAS score was 1.
3, and the disease activity was low; epilepsy did not recur
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 Figure 7: Analysis and thinking of changes in CRP and ESR levels during 4 and 24 weeks of treatment -B27 positive, and accompanied by imaging changes such as sacroiliitis, the diagnosis of AS is clear, and the assessment is highly active, with structural progress, functional impairment and limited activity; and epilepsy
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 ▎Treatment and medication: The patient suffers from two diseases at the same time, and the medication should be considered: ① AS: The patient's previous use of NSAIDs has not been effective, and biologics therapy should be initiated in time; the patient is more willing to relieve symptoms and restore and improve structure and function
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The current evidence-based evidence shows that secukinumab has outstanding advantages in delaying the long-term imaging progression of AS and maintaining structure and function, and secukinumab treatment in patients may better meet their treatment needs
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② Epilepsy: Studies have shown that IL-17A may be related to the pathogenesis of various neuroimmune diseases [13]; its expression level is not only significantly correlated with the frequency of seizures, but also highly correlated with the severity of epilepsy [14]
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In conclusion, the IL-17 signaling pathway may be involved in the pathogenesis of epilepsy, and secukinumab treatment may potentially improve the epilepsy condition of patients
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 For the above two considerations, the IL-17A inhibitor secukinumab was selected as the first-line biological agent for this AS patient with epilepsy
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In addition, the scheme is combined with sulfasalazine (a traditional synthetic disease-modifying anti-rheumatic drug, which has a certain effect on peripheral arthritis) and sodium valproate sustained-release tablets (anti-epileptic drug), in order to achieve a more ideal treatment in clinical practice effect
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 ▎Treatment evaluation: After receiving treatment, the patient's symptoms and activity were improved, and the level of inflammatory indicators was significantly reduced.
The overall effect was fast and the effect was significant; at the same time, epilepsy was also effectively controlled during the treatment
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Low back pain + osteophyte formation, how can AS patients who are troubled by the disease regain hope? Case details ▎Basic information of the patient: Male, 31 years old, admitted to hospital because of "8 years of low back pain and 6 years of hip pain"
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▎History of present illness: 8 years ago, there was no obvious incentive for persistent low back pain (mainly below the waist), with joint stiffness (worsening after getting up in the morning and sitting for a long time, improving after activities, especially at night)
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CT of the sacroiliac joint showed "rough sacroiliac joint surface", irregular diagnosis and treatment, and intermittent use of NSAIDs was effective; pain in both hips and knees with no obvious cause 6 years ago; spinal mobility limitation occurred 1 year ago; since the disease , patients with poor mental sleep
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▎Personal and family history: 10-year smoking history; no family history
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▎Physical examination: chronic disease appearance, abnormal gait; positive “4” test on both sides, hip tenderness; limited cervical spine movement, neck rotation 35°, occipital wall distance 12 cm; lumbar spine flexion and extension, left and right lateral flexion , limited rotation, finger-to-ground distance of 25 cm, positive Schober test (2 cm), and lumbar scoliosis of 5 cm
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▎Auxiliary examination: Laboratory examination: ESR 56.
0 mm/L, CRP 78.
10 mg/L; HLA-B27 positive; hepatitis B core antibody (HBcAb) positive, other negative, HBV-DNA negative; sacroiliac joint CT: bilateral sacroiliac Focal bone destruction on the articular surface, increased edge density, narrowing of the joint space, and partial fusion
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Similar changes were seen in the facet joints of the spine and bilateral hip joints
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It indicates spondyloarthropathy with bilateral hip joint involvement; Figure 8: CT of sacroiliac joints and enhanced MRI of sacroiliac joints: bilateral sacroiliac joint space is obviously narrowed, part of bony fusion, and patchy slightly longer T1, slightly longer T1, slightly fused under the articular surface.
Long T2 signal shadow, blurred articular surfaces
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There are multiple cystic long T1 and long T2 signal shadows in bilateral acetabulum (the above-mentioned changes in bilateral sacroiliac joints, most of which are AS)
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 Figure 9: Enhanced MRI of sacroiliac joint▎Admission diagnosis: ankylosing spondylitis
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▎AS disease activity assessment: ASDAS-CRP 4.
1, BASDAI 4.
7, highly active disease; activity function score: BASMI 4, BASFI 0.
5
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▎Therapeutic regimen: Irecoxib (NSAID) 0.
1 g bid orally, secukinumab 150 mg qw
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▎Follow-up and re-examination: After treatment, the patient's inflammatory index decreased to a stable level; the visual analogue scale (VAS) decreased, and the pain was relieved; the ASDAS-CRP disease activity decreased, and the disease activity was in a state of low disease activity; the limitation of joint activity was significantly improved compared with the previous one; the patient reignited Hope for life, to be able to work and live normally
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Analysis and thinking▎Clinical and pathological features of the patient: the patient had both axial and peripheral joint lesions; no synovitis was found in both knees and hip joints; no Achilles tendon attachment, plantar fascia, and tendons in both knee joints were found Enthesitis; however, osteophytes were present in both hips and right knee, and pathological new bone formation was present
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According to the patient's various examination results, the diagnosis of AS is clear, and the patient is in a high disease activity state
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Give aggressive treatment to inhibit further structural progression and avoid disability
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▎Therapeutic drugs: Consider from two perspectives of efficacy and safety: ① Efficacy: Considering that the patient's condition is highly active, spinal joint movement is limited, and there is pathological new bone formation, NSAIDs alone is not enough to improve disease progression.
The clinical efficacy of peripheral joint manifestations is also not significant, and it is necessary to initiate biologic therapy to achieve full control
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Among biological agents, the mechanism and clinical research data of IL-17A inhibitors in inhibiting new bone formation and delaying the progression of AS imaging are relatively substantial and prominent, and may play a greater role
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② Safety: When the patient was admitted to the hospital, the HBcAb was positive (indicating that he may have been infected with hepatitis B in the past but still in the recovery period), and the HBV-DNA was negative (the viral load was very low and not within the measurement range; viral replication may have been inhibited), As far as possible, safer biologics should be selected for patients to prevent hepatitis B virus (HBV) reactivation during treatment
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Compared with TNF-α inhibitors, the IL-17A inhibitor secukinumab has a lower probability of causing HBV reactivation, and no reports of increased risk of HBV reactivation have been found in previous studies [12]
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Therefore, considering the specific situation of this patient, it is an ideal choice to use secukinumab as a first-line biologic therapy
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 ▎Treatment evaluation: After treatment, the patient's inflammatory indicators were controlled; the joint pain and limitation of activities were significantly improved, and he was able to live, study and work normally
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As a first-line biological agent for this AS patient, secukinumab has demonstrated good efficacy and safety
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Expert Comments Professor Dai Shengming, Chief Physician and Doctoral Supervisor of the Department of Rheumatology and Immunology, Shanghai Sixth People's Hospital The patients in these two cases are both young males.
Before receiving standard treatment, partial fusion of the sacroiliac joints and spinal ligaments and bones had appeared.
Growth and hip joint damage, the body function was significantly damaged
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 The patient of case 1 missed the optimal treatment time window because he did not receive timely and accurate diagnosis
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Although the CT scan of the sacroiliac joint 8 years ago showed "rough sacroiliac joint surface" in the patient of case 2, it may be because the patient did not pay attention to it, the doctor was inexperienced, or the doctor did not explain it clearly to the patient.
It can be seen that, The patient did not adhere to the follow-up visit and missed the optimal treatment time window
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The above phenomena are common in the country
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It is hoped that through the sharing of these two cases, both our clinicians and patients can learn the following four lessons: 1.
Early diagnosis is very important.
The onset of AS is relatively insidious, and patients often do not pay attention to it in the early stage, and do not seek medical treatment in time; Due to the late development of rheumatology and immunology in China, and the influence of most disciplines is not large, there are still many tertiary hospitals that do not have rheumatology and immunology departments.
Patients often choose orthopedics as the first consultation department after low back pain, but most orthopaedics doctors Without knowing the early symptoms of AS, patients are often misdiagnosed as "lumbar muscle strain", "lumbar disc herniation or herniation", "hip tuberculosis", etc.
, and even receive surgical treatment by mistake
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To improve this phenomenon, we also need to vigorously strengthen multidisciplinary communication and popular science education, so as to promote the awareness and understanding of AS among orthopaedic surgeons and the majority of patients
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 2.
It is very important to insist on follow-up visits.
AS is a chronic progressive disease.
It usually takes about 10 years from the onset of symptoms to the appearance of joint structure deformation, and the symptoms are often intermittent.
Patients are prone to paralysis and do not receive standardized treatment
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If the patient insists on regular follow-up visits, the doctor can timely determine whether drug treatment is needed and whether the treatment plan needs to be adjusted according to the condition, so as to help the patient obtain a better prognosis and prevent damage to the joint structure as much as possible
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 3 Pay close attention to juvenile onset patients with concomitant hip damage There is a lot of clinical evidence that juvenile onset patients are at high risk for hip damage
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Hip ankylosis has a far greater negative impact on patients' quality of life and labor capacity than spinal ankylosis
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The receiving doctor should pay attention to whether there is any abnormality in hip pain or squatting movements of adolescent patients, and if necessary, check hip MRI for identification and verification
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As soon as evidence of hip involvement is found, an aggressive treatment plan should be instituted
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 4 Timely initiation of biologics The advent of biologics has greatly improved the clinical symptoms of patients with active AS
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The currently marketed biological agents that can be used for the treatment of AS include TNF-α inhibitors and IL-17 inhibitors
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For those patients with no clear effect after 2-4 weeks of NSAIDs treatment, or patients with symptomatic improvement after 12 weeks of NSAIDs treatment but still no clinical remission or low disease activity, or patients with active hip arthritis For patients, after exclusion of contraindications, biologics with a relatively clear effect of delaying the structural progression of AS should be initiated in a timely manner, such as IL-17A inhibitor secukinumab
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Summary The treatment process of the two cases in this issue reflects the actual effect of the IL-17A inhibitor secukinumab in the treatment of AS in the real world
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AS patients with high disease activity should start biologics in a timely manner
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According to the advantages of secukinumab, it can be used as a first-line biological treatment for AS patients with or about to develop osteophytes and need to inhibit new bone formation, which can not only rapidly control symptoms, reduce disease activity, but also It inhibits the formation of new bone, effectively delays the structural progress, and brings hope for the maintenance of the patient's functional state
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Did the case diagnosis and treatment shared in this issue help you? Did the incisive comments of the experts give you a new understanding and thinking about AS diagnosis and treatment? Do you want to learn more standardized diagnosis and treatment skills of AS, and understand the medication experience and experience of young and middle-aged doctors? More exciting contents in the "C Pioneer" case library are waiting for you to discover! See you next time! Comment expert Professor Dai Shengming Director of the Department of Rheumatology and Immunology, Shanghai Sixth People's Hospital, Chief Physician, Professor and Doctoral Supervisor In 2012, he was promoted to Chief Physician in the army, and the professor has successively presided over 1 project of the National 973 Program and 6 projects of the National Natural Science Foundation of China.
As the first author or corresponding author, he has published more than 20 SCI papers with a cumulative impact factor of more than 110 points, and edited works such as "Psoriatic Arthritis" as the first author or main author and won the National Science and Technology Progress Award 1 second prize, 1 first prize of Shanghai Science and Technology Progress Award, 2 second prizes of military medical achievements, 1 second prize of Shanghai Medical Science and Technology Award, and 3 third prizes of Shanghai or military achievements.
Rising Star of Science and Technology", the first prize of "Silver Snake Award", the highest honor of Shanghai medical and health system, "Excellent Doctor" in Shanghai, "Pujiang Talent" in Shanghai, etc.
He is also the vice chairman of Shanghai Rheumatology Branch and a member of Chinese Rheumatology Association.
, Member of Rheumatology and Immunology Branch of Chinese Medical Doctor Association, member of Rheumatology and Immunology Branch of Shanghai Medical Doctor Association and other case experts Professor Ding Shuang, MD, Deputy Chief Physician and Associate Professor of Rheumatology and Immunology Department of the First Affiliated Hospital of China Medical University, New York University Lange Member and Secretary of the Rheumatology Youth Committee of the Liaoning Medical Association, Visiting Scholar, Liaoning Medical Center, Executive Director of the Cell Research and Treatment Professional Committee of the Liaoning Provincial Society of Cell Biology, Member of the Rheumatology Professional Committee of the Liaoning Chinese Medicine Association Member, Member of the General Education Group of Rheumatology and Immunology, Cross-Strait Medical and Health Exchange Association References: [1] Lin Zhiming, et al.
Chinese Journal of Rheumatology.
2008, 12(6): 375-378.
[2]Schett G, et al.
Nat Rev Rheumatol.
2017, 13: 731-41.
[3] Suzuki E, et al.
Autoimmun Rev.
2014, 13(0): 496–502.
[4] Ellen M Gravallese, et al.
Nat Rev Rheumatol.
2018, 14(11):
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