ABSTRACT
Introduction: Efgartigimod is effective and well-tolerated in patients with anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG). However, the therapeutic potential and the safety profile of efgartigimod in myasthenic crisis (MC) remained largely unknown. Methods: This is an observational, prospective, multicenter, real-world study to follow 2 MC patients who initiated efgartigimod as a first-line rescue therapy and 8 cases who used it as an add-on therapy. Baseline demographic features and immunotherapies were collected, and the MG-activities of daily living (MG-ADL) scale was evaluated every week since efgartigimod treatment for 8 weeks. Additionally, serum IgG and anti-AChR antibody levels and the peripheral CD4+ T lymphocytes were measured before and after one cycle of treatment. Results: Ten patients with MC were enrolled in the study, including 9 anti-AChR antibody positive and 1 anti-muscle-specific kinase (MuSK) positive. All patients were successfully weaned from the ventilation after receiving efgartigimod treatment, with a length of 10.44 ± 4.30 days. After one cycle of infusions, the MG-ADL score reduced from 15.6 ± 4.4 at the baseline to 3.4 ± 2.2, while the corticosteroid dose was tapered from 55.0 ± 20.7 mg to 26.0 ± 14.1 mg. The proportions of regulatory T cells and naïve T cells (% in CD4+ T) significantly decreased post-efgartigimod treatment (5.48 ± 1.23 vs. 6.90 ± 1.80, P=0.0313, and 34.98 ± 6.47 vs. 43.68 ± 6.54, P=0.0313, respectively). Conclusion: These findings validated the rapid action of efgartigimod in facilitating the weaning process with a good safety profile in patients with MC.
Subject(s)
Myasthenia Gravis , Humans , Female , Male , Myasthenia Gravis/drug therapy , Myasthenia Gravis/immunology , Middle Aged , Prospective Studies , Adult , Aged , Treatment Outcome , Autoantibodies/blood , Autoantibodies/immunology , Receptors, Cholinergic/immunology , Drug Therapy, Combination , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/drug effectsABSTRACT
Background: Efgartigimod (Efgartigimod alpha fcab, Vyvgart™) is a pioneering neonatal Fc receptor (FcRn) antagonist for the treatment of severe autoimmune diseases mediated by pathogenic immunoglobulin G (IgG) autoantibodies, including myasthenia gravis (MG). It is a well-tolerated drug with minor side effects, such as headache and upper respiratory (lung) and urinary tract infections. Here, we present a case of Kaposi's varicelliform eruption (KVE) and herpetic conjunctivitis related to efgartigimod in a 60-year-old patient with ocular MG (OMG). Case description: A 60-year-old Chinese male suffered from acetylcholine receptor antibody positive (AChR Ab+) OMG for 8 years. During this period, he underwent first-line treatment with systemic corticosteroids, cyclosporine, cyclophosphamide, and so on, but had poor symptom improvement. On the recommendation of his attending neurologist, he received one cycle of intravenous efgartigimod (10mg/kg, once weekly for 4 weeks). The patient experienced fever, widespread painful blisters, and edema on the face on the third day after his last intravenous infusion. The patient also complained of increased secretions and a foreign body sensation in both eyes. Laboratory tests confirmed infection with herpes simplex virus (HSV). A diagnosis of efgartigimod-associated KVE and herpetic conjunctivitis was made. After intravenous administration (5mg/kg, 3 times a day, every 8 hours) for 10 days, the patient was cured without residual complications. Conclusions: This case is the first report of a patient with KVE and herpetic conjunctivitis related to efgartigimod in PubMed. This is rare and unusual. Clinicians should be alert to the rare symptoms related to efgartigimod.
Subject(s)
Kaposi Varicelliform Eruption , Myasthenia Gravis , Humans , Male , Middle Aged , Myasthenia Gravis/drug therapy , Myasthenia Gravis/chemically induced , Myasthenia Gravis/immunology , Myasthenia Gravis/diagnosis , Kaposi Varicelliform Eruption/drug therapy , Herpes Simplex/drug therapy , Herpes Simplex/diagnosis , Herpes Simplex/immunology , Conjunctivitis, Viral/drug therapy , Conjunctivitis, Viral/diagnosisABSTRACT
Therapeutic plasma exchange (TPE) is used as an effective treatment modality for a variety of autoimmune disorders. Apart from its desired effect of removing pathological blood components, it also can remove coagulation factors and drugs. Currently, there is an insufficient amount of information regarding the use of direct oral anticoagulants in this setting. In this article, we present a case report of a patient with myasthenia gravis and chronic anticoagulation with apixaban who underwent a series of TPE while continuing apixaban treatment. We observed that only 10% of daily dose was removed by the procedure and plasma levels of apixaban corresponded with expected range. TPE was not associated with shortened drug plasma half-life. We did not observe any significant alteration of apixaban pharmacokinetics during the period of TPE therapy, as well as no thrombotic or bleeding events. This case report supports the use of apixaban in patients treated by TPE, nevertheless, to firmly establish apixaban efficacy and safety profile in this clinical setting further research is needed.
Subject(s)
Factor Xa Inhibitors , Plasma Exchange , Pyrazoles , Pyridones , Humans , Pyridones/administration & dosage , Pyrazoles/administration & dosage , Pyrazoles/pharmacokinetics , Plasma Exchange/methods , Factor Xa Inhibitors/administration & dosage , Myasthenia Gravis/drug therapy , Myasthenia Gravis/therapy , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Female , Middle Aged , Half-Life , Male , AgedABSTRACT
Myasthenia gravis (MG) is an autoimmune disease that targets neuromuscular junctions. While immunotherapy remains the cornerstone of treatment, the effects of Janus kinase (JAK) inhibitors on MG remain underexplored. In this report, we describe the case of a 58-year-old woman with ocular myasthenia gravis who received treatment with the JAK inhibitor, baricitinib for alopecia areata. The patient presented with left eyelid ptosis and an inadequate response to steroids and pyridostigmine, along with symptoms of alopecia areata. Following diagnosis, we initiated a treatment regimen consisting of baricitinib for six months. After initiation of baricitinib, we observed a complete resolution of the patient's MG symptoms, accompanied by hair regrowth, even when steroids were tapered and pyridostigmine was discontinued. Furthermore, the titer of the anti-acetylcholine receptor antibody was decreased. This report represents the first reported case of anti-acetylcholine receptor antibody-positive MG that was successfully treated through the inhibition of JAK activity.
Subject(s)
Azetidines , Myasthenia Gravis , Purines , Pyrazoles , Sulfonamides , Humans , Myasthenia Gravis/drug therapy , Azetidines/therapeutic use , Female , Middle Aged , Sulfonamides/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Treatment Outcome , Receptors, Cholinergic/immunologyABSTRACT
OBJECTIVE: Efgartigimod, a neonatal Fc receptor antagonist, facilitates antibody degradation including pathogenic IgGs. The ADAPT study demonstrated the tolerability and efficacy of efgartigimod in the treatment of generalized myasthenia gravis (gMG). However, very limited evidence is available for the Chinese population, and it remains inconclusive about which kind of patients are selected to preferentially receive efgartigimod in real-world settings. METHODS: This multicenter cohort study included gMG patients treated at 14 neuromuscular reference centers in China. The Myasthenia Gravis Activities of Daily Living (MG-ADL) score, immunosuppressants, and the incidence of treatment-emergent adverse events (TEAEs) were prospectively collected. RESULTS: Of the 1640 gMG admitted between September and December 2023, 61 (3.7%) received efgartigimod for at least one treatment cycle. Among them, 56 cases (92%) were anti-AChR antibody-positive, 4 were anti-MuSK antibody-positive, and 1 was seronegative. Thymoma-associated myasthenia gravis accounted for most cases (44%, 27 out of 61). The principal causes of efgartigimod initiation included MG acute exacerbation (MGAE) (48%, 29 out of 61) and myasthenic crisis (MC) (15%, 9 out of 61). Clinically meaningful improvement was rapidly achieved in 97% (58 out of 61) of patients at 1.3 ± 0.7 weeks. By week 12, the MG-ADL score reduced to 3.8 ± 4.1 (baseline:10.5 ± 5.2) for all participants, while it reduced to 4.0 ± 4.7 for MGAE and 3.8 ± 4.2 for MC, respectively. All but one TMG patient required no additional rescue therapies after efgartigimod initiation. 11.5% (7 out of 61) reported ≥1 TEAEs. INTERPRETATION: This multicenter cohort study demonstrated the efficacy of efgartigimod in rapid control of gMG. Patients with MGAE or MC would benefit from efgartigimod treatment.
Subject(s)
Myasthenia Gravis , Humans , Myasthenia Gravis/drug therapy , Male , Middle Aged , Female , China , Adult , Cohort Studies , Aged , Receptors, Fc , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic useABSTRACT
BACKGROUNDS AND OBJECTIVES: Early use of immunosuppression has been suggested to prevent generalization of ocular myasthenia gravis (OMG), but high-quality evidence is limited in this regard. We examined whether treatment with prednisone and other immunosuppressants reduce the risk of generalization in OMG. METHODS: This is a retrospective study of consecutive adults with pure OMG who had a minimum 6 months of follow-up. The main outcome was the time to developing generalized symptoms. We used propensity scores to create matched data sets of patients treated with prednisone or any immunosuppressant vs controls. We also used unmatched models with inverse probability of treatment weights (IPTW) and variable exposure times. We used Cox proportional hazards model to estimate hazard ratio (HR) for generalization, comparing treated patients vs controls. RESULTS: A total of 154 patients were included, with a mean follow-up of 87.4 ± 73 months since onset. Forty-three (28%) were generalized, and mean time to generalization from diagnosis was 24.2 ± 24.1 months. Patients who received prednisone had lower risk of generalization than controls, with pooled HR 0.43 (95% CI 0.19-1.06) for the matched model, HR 0.46 (95% CI 0.21-0.89) for the IPTW model, and for HR 0.44 (95% CI 0.23-0.81) for the time-dependent exposure model. Patients who received any immunosuppressant had lower risk of generalization, with HR 0.30 (95% CI 0.11-0.77), 0.32 (95% CI 0.14-0.70), and 0.35 (95% CI 0.15-0.80) for the matched, IPTW, and IPTW-varying exposure models, respectively. DISCUSSION: Our study provides evidence that steroidal and nonsteroidal immunosuppression in patients with OMG is associated with a reduced risk of developing generalized symptoms over time. This supports the early use of immunosuppression in this population. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that treatment of OMG with corticosteroids or nonsteroidal immunosuppressants reduces the risk of generalization.
Subject(s)
Immunosuppressive Agents , Myasthenia Gravis , Prednisone , Humans , Myasthenia Gravis/drug therapy , Male , Female , Retrospective Studies , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Middle Aged , Prednisone/therapeutic use , Adult , Aged , Cohort Studies , Follow-Up Studies , Immunosuppression Therapy/adverse effects , Proportional Hazards ModelsABSTRACT
Paraneoplastic syndrome is a broad spectrum of signs and symptoms due to neoplasm, attributed to substances produced by tumor cells, or in response to it. Myasthenia gravis (MG) is a well-known paraneoplastic neurological syndrome (PNS), frequently associated with thymic abnormalities, but rarely reported in patients with lymphoplasmacytic lymphoma.This study presents the case of a 52-year-old Indonesian male patient who was diagnosed with Waldenstrom macroglobulinemia (WM), a rare B-cell neoplasm, after developing a new onset of MG with myasthenic crisis. the patient's MG features improved with Ibrutinib as a treatment targeted toward cancer. This is the first case report presenting the treatment response of Ibrutinib in WM with myasthenic crisis. The literature was reviewed to explain the possibility of MG as a paraneoplastic syndrome of WM and the treatment response of Ibrutinib for this patient, as well as summarizing previous case reports of concomitant MG and WM.MG should be considered a paraneoplastic malignancy syndrome, including WM, during diagnostic workup. Ibrutinib should also be considered when available to patients, due to its adequate response in both previously treated and treatment naïve patients.
Subject(s)
Adenine , Myasthenia Gravis , Piperidines , Pyrazoles , Pyrimidines , Waldenstrom Macroglobulinemia , Humans , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/complications , Male , Adenine/analogs & derivatives , Adenine/therapeutic use , Middle Aged , Piperidines/therapeutic use , Myasthenia Gravis/drug therapy , Myasthenia Gravis/complications , Myasthenia Gravis/diagnosis , Pyrimidines/therapeutic use , Pyrazoles/therapeutic use , Paraneoplastic Syndromes, Nervous System/drug therapy , Paraneoplastic Syndromes, Nervous System/etiology , Treatment OutcomeABSTRACT
Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who experience acute exacerbations and do not respond to conventional treatments, there is an urgent need to find more suitable treatment options. With the advent of biologic agents, efgartigimod has shown promising results in the treatment of MG. We report a 65-year-old MuSK-MG patient who presented with impaired eye movements initially, and the symptoms rapidly worsened within a week, affecting the limbs and neck muscles, and had difficulties in chewing and swallowing. Lymphoplasmapheresis did not achieve satisfactory results, but after a cycle of efgartigimod treatment, the patient's symptoms gradually improved and remained in a good clinical state for several months.
Subject(s)
Myasthenia Gravis , Receptors, Cholinergic , Humans , Myasthenia Gravis/drug therapy , Aged , Receptors, Cholinergic/immunology , Treatment Outcome , Receptor Protein-Tyrosine Kinases/immunology , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Autoantibodies/immunology , Autoantibodies/blood , Male , FemaleABSTRACT
BACKGROUND: Myasthenia gravis (MG) is a long-term autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue as its primary clinical features. Vitamin D is crucial for both the autoimmune response and skeletal muscle function. CASE PRESENTATION: Here, we presented a case report documenting the substantial improvement in symptoms experienced by a patient who underwent subtotal gastrectomy for gastric cancer following high-dose Vitamin D supplementation. The patient developed generalized MG two months after the surgery and did not respond adequately to pyridostigmine therapy, experiencing a progressive deterioration of the condition. A significant reduction in vitamin D concentration was observed following subtotal gastrectomy. In response, high-dose vitamin D supplementation was administered to the patient. Within one week of treatment, swallowing symptoms improved, enabling the consumption of a small amount of liquid food. By the second week, substantial swallowing and neck function improvements were evident. After one month, the patient regained the ability to straighten the neck while walking and consumed a regular diet despite persistent difficulties chewing hard food. CONCLUSIONS: This case underscores the therapeutic potential of vitamin D in alleviating MG symptoms, particularly in individuals with compromised vitamin D levels following gastrectomy. The observed improvements present a new perspective on the possible involvement of vitamin D supplementation in the management of postoperative MG cases.
Subject(s)
Gastrectomy , Myasthenia Gravis , Vitamin D , Humans , Gastrectomy/adverse effects , Myasthenia Gravis/surgery , Myasthenia Gravis/drug therapy , Vitamin D/therapeutic use , Vitamin D/administration & dosage , Stomach Neoplasms/surgery , Male , Female , Aged , Middle Aged , Dietary SupplementsABSTRACT
BACKGROUND: Eculizumab and efgartigimod were approved to treat anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (anti-AChR Ab-positive gMG). These relatively new biological treatments provide a more rapid onset of action and improved efficacy compared with conventional immunosuppressive treatments, but at a higher cost. OBJECTIVE: To assess the cost-effectiveness of eculizumab and, separately, efgartigimod, each added to conventional therapy vs conventional therapy alone, among patients with refractory anti-AChR Ab-positive gMG and those with anti-AChR Ab-positive gMG, respectively. METHODS: A Markov model with 4 health states was developed, evaluating costs and utility with a 4-week cycle length and lifetime time horizon from a health care system perspective and a modified societal perspective including productivity losses from patients and caregiver burden. Model inputs were informed by key clinical trials and relevant publications identified from targeted literature reviews, and drug costs were identified from Micromedex Red Book. Costs and outcomes were discounted at 3% per year. Incremental cost-effectiveness ratios (ICERs; cost per quality-adjusted life-year [QALY] gained) were calculated for each comparison. RESULTS: Among the corresponding populations, lifetime costs and QALYs, respectively, for eculizumab were $5,515,000 and 11.85, and for conventional therapy, $308,000 and 10.29, resulting in an ICER of $3,338,000/QALY gained. For efgartigimod, lifetime costs and QALYs, respectively, were $6,773,000 and 13.22, and for conventional therapy, $322,000 and 9.98, yielding an ICER of $1,987,000/QALY gained. After applying indirect costs in a modified societal perspective, the ICERs were reduced to $3,310,000/QALY gained for eculizumab and $1,959,000/QALY gained for efgartigimod. CONCLUSIONS: Eculizumab and efgartigimod are rapidly acting and effective treatments for myasthenia gravis. However, at their current price, both therapies greatly exceeded common cost-effectiveness thresholds, likely limiting patient access to these therapies.
Subject(s)
Antibodies, Monoclonal, Humanized , Cost-Benefit Analysis , Markov Chains , Myasthenia Gravis , Quality-Adjusted Life Years , Receptors, Cholinergic , Humans , Myasthenia Gravis/drug therapy , Myasthenia Gravis/economics , Myasthenia Gravis/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/economics , Receptors, Cholinergic/immunology , Female , Male , Middle Aged , Drug Costs , Adult , AutoantibodiesABSTRACT
INTRODUCTION/AIMS: Efgartigimod, a neonatal Fc-receptor inhibitor, has recently been approved as treatment for myasthenia gravis (MG). In this retrospective cohort study, we aimed to systematically assess short- and long-term effectiveness of efgartigimod in patients with refractory MG. METHODS: Sixteen patients with refractory autoimmune acetylcholine receptor MG were treated with efgartigimod. Data were collected from January 2021 to March 2023 on Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis score (QMG), Myasthenia Gravis Composite score (MGC) and the 15-item revised version of the Myasthenia Gravis Quality of Life questionnaire (MG-QoL15r). RESULTS: A favorable outcome was seen in 56% of patients at the last measurement. Out of 16 patients, 50% were an MG-ADL responder after the first treatment cycle. After 4 weeks, a clinically meaningful improvement compared to baseline was seen on the MG-ADL, QMG, and MGC. There was a statistically significant improvement on the MGQoL15r from baseline to week 4. The improvement was maintained until the last measurement for the MGC and the MGQoL15r. At the last visit, all patients had discontinued 4-weekly dosages, shifting to administration frequencies of 1, 2, or 3 weeks. Drug doses could be decreased for prednisolone (n = 7), azathioprine (n = 2), and intravenous immunoglobulin (n = 9). Frequency of plasma exchange was decreased in nine patients. DISCUSSION: In patients with refractory MG, efgartigimod was effective for at least half of all patients. Patients required more frequent dosing compared to the ADAPT phase 3 trial. In 80% of the patients concurrent medication could be reduced or discontinued.
Subject(s)
Myasthenia Gravis , Quality of Life , Humans , Myasthenia Gravis/drug therapy , Male , Female , Middle Aged , Retrospective Studies , Adult , Aged , Activities of Daily Living , Treatment Outcome , Cohort StudiesABSTRACT
INTRODUCTION/AIMS: The impact of treatment expectations on active treatment outcomes has not been specifically investigated in neuromuscular disorders. We thus explored in myasthenia gravis (MG) the contribution of patients' pre-treatment expectations combined with an immunosuppressant drug on treatment outcomes. METHODS: This pilot correlational study involved 17 patients with generalized MG, scheduled to start immunosuppressant azathioprine. At baseline, a healthcare professional administered: (i) the Stanford Expectations of Treatment Scale; (ii) a structured checklist paper form asking patients which side-effects they expected to develop after starting azathioprine, coupled with a standardized framing of statements. Quantitative Myasthenia Gravis (QMG) score and daily dose of concomitant drugs were assessed by neurologists as clinical outcomes. Clinical outcomes and side-effects were re-assessed at 3 and 6 months, and clinical outcomes were monitored at 18 months. RESULTS: Clinically significant improvement in the QMG scores was achieved at 3 or 6 months. The level of state anxiety appeared to act as moderator of pre-treatment negative expectations (strong, positive, indicative correlation, rs = .733, p = .001). The latter were, in turn, associated with the fulfillment of side-effects that patients expected to develop with the new treatment (moderate, positive, indicative correlation, rs = .699, p = .002). No significant correlation emerged between positive and negative expectations. DISCUSSION: Our findings show a very quick clinical response and also suggest that patients' expectations and anxiety contributed to treatment outcomes, highlighting the importance of promoting safety messages and education strategies around newly introduced treatments. Future goals include evaluating a larger cohort that includes a matched control group.
Subject(s)
Azathioprine , Immunosuppressive Agents , Myasthenia Gravis , Humans , Myasthenia Gravis/drug therapy , Myasthenia Gravis/psychology , Pilot Projects , Male , Female , Middle Aged , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Treatment Outcome , Adult , Aged , Azathioprine/therapeutic use , Anxiety/etiology , Anxiety/psychologyABSTRACT
INTRODUCTION: Rituximab (RTX) has been proven effective in managing refractory generalized myasthenia gravis (MG), and its use is increasing worldwide. MG stabilization may initially require oral corticosteroid (CS) therapy, but its long-term side effects require the shortest duration of treatment. We studied the clinical effectiveness and usefulness of corticosteroids associated with RTX compared to RTX alone on MG remission. METHODS: In a monocentric retrospective cohort in the Nice University Hospital, we compared naïve MG patients treated with RTX as first-line therapy alone (G1) or associated with CS (G2). After the RTX induction, we evaluated efficacy with the Osserman score (OS) and the requirement for any rescue therapy (IVIg or plasmapheresis). RESULTS: Sixty-eight patients were treated with RTX, of which 19 (27.94%) benefited from an association with at least 0.5 mg/kg of corticosteroids. RTX-CS patients were more severe than RTX alone (OS for G1: 74.1 and G2: 64.94, p = 0.044). However, OS at 3 (83.44 and 83.12, p = 0.993), 6 (88.69 and 86.36, p = 0.545), 9 (82.91 and 85.73, p = 0.563), and 12 months (86.6 and 88.69, p = 0.761) from the treatment induction were similar. Rescue therapy following RTX induction was significantly higher for the RTX-CS (20.41% and 47.37%, p = 0.037). Regarding safety, adverse event rates were similar in the two groups (0% and 14.29%, p = 0.178). CONCLUSION: We suggest that RTX alone is as effective as RTX-CS in MG patients, indicating that avoiding steroids could reduce side effects, decrease rescue therapies, and not affect MG outcomes.
Subject(s)
Adrenal Cortex Hormones , Myasthenia Gravis , Rituximab , Humans , Myasthenia Gravis/drug therapy , Rituximab/pharmacology , Rituximab/administration & dosage , Rituximab/therapeutic use , Rituximab/adverse effects , Male , Female , Middle Aged , Adult , Retrospective Studies , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Drug Therapy, Combination , Immunologic Factors/administration & dosage , Immunologic Factors/pharmacology , Aged , Treatment Outcome , Young AdultABSTRACT
With the advancement of cancer treatment technologies, immunotherapy has begun to be widely utilized. Colon cancer is one of the most common types of cancer, with metastasis being a frequent occurrence in late-stage patients. Hence, immunotherapy, as an emerging and potentially effective treatment modality, merits exploration to enhance patient survival rates and clinical benefits. However, various immune-related adverse events cannot be entirely avoided. Myasthenia gravis induced by immunotherapy serves as a rare but potentially lethal adverse event, and it has been increasingly reported. Understanding the mechanisms of irAEs can aid in controlling the side effects induced by treatment. Here, we reported a case of myasthenia gravis occurring after anti-PD-1 therapy for late-stage colon cancer.
Subject(s)
Colonic Neoplasms , Immune Checkpoint Inhibitors , Myasthenia Gravis , Humans , Myasthenia Gravis/chemically induced , Myasthenia Gravis/drug therapy , Colonic Neoplasms/drug therapy , Immune Checkpoint Inhibitors/adverse effects , Male , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Middle Aged , Programmed Cell Death 1 Receptor/antagonists & inhibitorsABSTRACT
BACKGROUND: Immune checkpoint inhibitors are a relatively new advancement in the world of cancer therapy. As such, their adverse effects have yet to be fully understood, with only recent literature documenting autoimmune phenomena secondary to their utilization. Specific immune checkpoint inhibitors have recently been linked with the development of myasthenia gravis, which is classically known to manifest spontaneously in patients. Given the relative rarity of this presentation, the risk of misdiagnosis and subsequent mortality and morbidity is concerning. CASE PRESENTATION: We discuss the case of a 73-year-old male who presented with clinical symptoms of myasthenia gravis and myositis shortly after beginning treatment with Pembrolizumab. The diagnosis of myasthenia gravis was initially missed at an outside hospital, which delayed initiation of proper treatment. CONCLUSION: While the incidence of "de-novo" diseases secondary to immune checkpoint inhibitors might be increasing, guidelines regarding best treatment options do not yet exist, leaving many providers at a loss when faced with making clinical decisions surrounding patients with De novo myasthenia gravis. Thus, our goal is to underscore the importance of early recognition of this disease, and emphasize the need for a standard of care as immune checkpoint inhibitors usage becomes more prevalent.
Subject(s)
Antibodies, Monoclonal, Humanized , Myasthenia Gravis , Myositis , Humans , Myasthenia Gravis/chemically induced , Myasthenia Gravis/drug therapy , Myasthenia Gravis/diagnosis , Male , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Myositis/chemically induced , Myositis/diagnosis , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Immune Checkpoint Inhibitors/adverse effectsABSTRACT
BACKGROUND: We aimed to compare the efficacy of tocilizumab with conventional immunotherapy in refractory patients with acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). METHODS: This single-center prospective cohort study was based on patients from an MG registry study in China and conducted from February 10, 2021 to March 31, 2022. Adult refractory patients with AChR-Ab+ gMG were assigned to tocilizumab or conventional immunotherapy groups. The primary efficacy outcome was the mean difference of MG activities of daily living (MG-ADL) change at weeks 4, 8, 12, 16, 20, 24 corresponding to that at the baseline between the two groups. A generalized estimating equation model was used for the primary outcome analysis. Safety was assessed based on adverse events. RESULTS: Of 34 eligible patients, 20 (mean [standard deviation] age, 53.8 [21.9] years; 12 [60.0%] female) received tocilizumab and 14 received conventional immunotherapy (45.8 [18.0] years; 8 [57.1%] female). The tocilizumab group had greater reduction in MG-ADL score at week 4 (adjusted mean difference, -3.4; 95% CI, -4.7 to -2.0; p < 0.001) than the conventional immunotherapy group, with significant differences sustained through week 24 (adjusted mean difference, -4.5; 95% CI, -6.4 to -2.6; p < 0.001). At week 24, the proportion of patients achieving higher levels of MG-ADL (up to 7-point reduction) and QMG (up to 11-point reduction) scores improvement was significantly greater with tocilizumab. Tocilizumab had acceptable safety profiles without severe or unexpected safety issues. CONCLUSION: Tocilizumab is safe and effective in improving the MG-ADL score and reducing prednisone dose in refractory AChR-Ab+ gMG, suggesting tocilizumab has the potential to be a valuable therapeutic option for such patients.