FREQUENTLY ASKED QUESTIONS (FAQs)
Managing generalized myasthenia gravis (gMG)
In gMG, pathogenic immunoglobulin G (IgG) autoantibodies attack key proteins on the postsynaptic membrane involved in signal transmission at the neuromuscular junction. This impairs signal transduction and muscle contraction, which leads to debilitating muscle weakness and fatigue.1,2
Learn more about the pathophysiology of gMG.
gMG=generalized myasthenia gravis.
gMG is a chronic, unpredictable, neuromuscular autoimmune disease. It is characterized by muscle weakness and fatigue that worsens with activity and improves with rest.3,4
Learn more about the symptoms of gMG.
gMG=generalized myasthenia gravis.
Patient treatment goals center around symptom management.5
See how tracking MG-ADL can help your patients communicate their progress to you.
gMG=generalized myasthenia gravis; MG-ADL=Myasthenia Gravis Activities of Daily Living.
The majority (95%) of patients with gMG have anti-AChR or anti-MuSK antibodies.6
Learn more about the antibody types in gMG.
AChR=acetylcholine receptor; gMG=generalized myasthenia gravis; MuSK=muscle-specific tyrosine kinase.
AChR and MuSK are among the key proteins in the postsynaptic membrane that are affected in gMG.2
- AChR autoantibodies result in pathology through any of the following 3 mechanisms: preventing acetylcholine from binding, reducing receptor density, and activating the complement system2
- MuSK autoantibodies also exert a pathogenic effect in gMG. While MuSK autoantibodies do not activate the complement pathway as with AChR autoantibodies, they contribute to a progressive loss of acetylcholine receptors and subsequent synaptic failure—and are often associated with more severe manifestations of the disease2,7
Gain a better understanding of AChR and MuSK autoantibodies.
Ab+=antibody positive; AChR=acetylcholine receptor; gMG=generalized myasthenia gravis; MuSK=muscle-specific tyrosine kinase.
Patients with anti-MuSK Ab+ gMG are primarily female, with onset of disease occurring in their late 20s and 30s, with higher rates in African Americans and Asians.7-9
Learn more about anti-MuSK Ab+ gMG.
Ab+=antibody positive; gMG=generalized myasthenia gravis; MuSK=muscle-specific tyrosine kinase.
Symptoms of anti-MuSK Ab+ gMG may be associated with a more severe manifestation of gMG because bulbar muscle involvement is predominant. Symptoms of anti-MuSK gMG include ptosis, diplopia, dysarthria, dysphonia with nasal voice, dysphagia, masticatory difficulty, muscle atrophy in face and tongue, and jaw muscle fatigue.7,8
Understand more about anti-MuSK Ab+ gMG.
Ab+=antibody positive; gMG=generalized myasthenia gravis; MuSK=muscle-specific tyrosine kinase.
Targeted therapies for gMG address the mechanism of disease. In recent years, therapies that target the disease pathophysiology of gMG, like FcRn blockers and complement inhibitors, have begun to emerge in the gMG treatment landscape. Although more real-world experience is needed with these treatments, they have the potential to positively impact treatment of patients with gMG.10,11
FcRn=neonatal Fc receptor; gMG=generalized myasthenia gravis.
In recent years, MSE has become a treatment goal for patients with gMG. It is defined as an MG-ADL score of 0 to 1 and is a useful tool to measure treatment effectiveness.12,13
gMG=generalized myasthenia gravis; MG-ADL=Myasthenia Gravis Activities of Daily Living.
Treatment with RYSTIGGO
RYSTIGGO is the first and only FDA-approved targeted treatment for adults with either anti-AChR Ab+ or anti-MuSK Ab+ gMG. In a Phase 3 clinical trial, RYSTIGGO demonstrated statistically significant improvements vs placebo in MG-ADL total score to Week 6 (-3.4 vs -0.8; P<0.001), with improvement observed as early as Week 1.3,14
Ab+=antibody positive; AChR=acetylcholine receptor; gMG=generalized myasthenia gravis; MG-ADL=Myasthenia Gravis Activities of Daily Living; MuSK=muscle-specific tyrosine kinase.
Yes. RYSTIGGO was evaluated in a subgroup of patients with anti-MuSK Ab+ gMG. It is the first and only FDA-approved treatment for adults with either anti-MuSK Ab+ or anti-AChR Ab+ gMG.14
See anti-MuSK Ab+ subgroup analysis.
Ab+=antibody positive; AChR=acetylcholine receptor; gMG=generalized myasthenia gravis; MuSK=muscle-specific tyrosine kinase.
RYSTIGGO is an FcRn blocker and a targeted therapy for gMG. It is a monoclonal antibody, or mAb, specifically designed to bind to FcRn with high affinity in adults with either anti-AChR Ab+ or anti-MuSK Ab+ gMG. High-affinity binding allows RYSTIGGO to compete with other IgGs—including AChR and MuSK pathogenic autoantibodies for the binding site on FcRn. IgGs bound to FcRn are protected from lysosomal degradation. Unbound autoantibodies are vulnerable to lysosomal degradation.1,14,15*
*The precise mechanism through which RYSTIGGO exerts therapeutic effects in gMG is unknown.
Learn more about the mechanism of action of RYSTIGGO.
Ab+=antibody positive; AChR=acetylcholine receptor; FcRn=neonatal Fc receptor; gMG=generalized myasthenia gravis; IgG=immunoglobulin G; MuSK=muscle-specific tyrosine kinase.
The efficacy of RYSTIGGO for the treatment of adults with either anti-AChR Ab+ or anti-MuSK Ab+ gMG was established in a Phase 3, randomized, double-blind, placebo-controlled study. The primary endpoint was the change from baseline between treatment groups in the MG-ADL total score to Week 6 (Day 43). QMG, MGC, and MG Symptoms PRO were also evaluated during the RYSTIGGO pivotal study.3,14*
See the Clinical Trial Results for RYSTIGGO.
*During the treatment period, RYSTIGGO or placebo were administered subcutaneously once a week for 6 weeks.14
Ab+=antibody positive; AChR=acetylcholine receptor; gMG=generalized myasthenia gravis; MG-ADL=Myasthenia Gravis Activities of Daily Living; MGC=myasthenia gravis composite; MG Symptoms PRO=Myasthenia Gravis Symptoms Patient-Reported Outcomes; MuSK=muscle-specific tyrosine kinase; QMG=quantitative myasthenia gravis.
Yes. MSE was assessed in the overall population of the RYSTIGGO pivotal study.3
MSE was an exploratory endpoint and not controlled for multiplicity. Therefore, data should be interpreted with caution and conclusions cannot be drawn.
MG Symptoms PRO is a novel outcome measure developed by UCB that complements established clinical outcome measures and was a secondary endpoint evaluated in the RYSTIGGO clinical trials. It is the only MG clinical outcome measure to have a standalone assessment of physical fatigue. In the RYSTIGGO pivotal study, 3 domains from the MG Symptoms PRO were evaluated: muscle weakness fatigability, physical fatigue, and bulbar muscle weakness.3,16,17
See the Clinical Trial Results for RYSTIGGO.
MG=myasthenia gravis; MG Symptoms PRO=Myasthenia Gravis Symptoms Patient-Reported Outcomes.
In a clinical study, adults taking RYSTIGGO experienced statistically significant improvement vs placebo in MG-ADL total score at Week 6 (-3.4 vs -0.8, P<0.001), with improvements observed as early as Week 1.14
See the Clinical Trial Results for RYSTIGGO.
MG-ADL=Myasthenia Gravis Activities of Daily Living.
In the pivotal study, RYSTIGGO achieved maximum efficacy at Week 6. These results are based on the primary endpoint, which evaluated the change from baseline to Week 6 (Day 43) in MG-ADL total score.14*
*During the treatment period, RYSTIGGO or placebo were administered subcutaneously once a week for 6 weeks.14
MG-ADL=Myasthenia Gravis Activities of Daily Living.
Yes. Patients from the RYSTIGGO treatment groups in the pivotal study (MycarinG) were eligible to enroll in 2 extension studies (MG0004 and MG0007).3,18,19
MG0004 was a 60-week, multicenter, randomized, Phase 3 extension study that included 71 adult patients from MycarinG who met eligibility criteria. Patients received RYSTIGGO once weekly for a period of 52 weeks, followed by 8 weeks of observation. MG0004 enrollment was closed upon the initiation of study MG0007.18,20
MG0007 was a Phase 3, multicenter study that included 165 adults from MycarinG and MG0004, which assessed the long-term safety, tolerability, and efficacy of RYSTIGGO given in repeated 6-week cycles, based on the manifestations of gMG symptoms.19,20
See the long-term safety data.
See the long-term efficacy data.
gMG=generalized myasthenia gravis.
Safety and Dosing of RYSTIGGO
The safety of RYSTIGGO was demonstrated in a Phase 3 clinical study. The most common adverse reactions (≥10%) reported by adults treated with RYSTIGGO were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea.3,14
Based on the Phase 3 clinical study, RYSTIGGO may increase the risk of infection and serious adverse reactions of aseptic meningitis have been reported. Hypersensitivity reactions, including angioedema and rash, were also observed.3,14
Concomitant use of RYSTIGGO with medications that bind to the human neonatal FcRn receptor (immunoglobulin products, monoclonal antibodies, or antibody derivatives containing the human Fc domain of the IgG subclass) may lower systemic exposure and reduce effectiveness of these medications.14
FcRn=neonatal Fc receptor; IgG=immunoglobulin G.
There are no contraindications associated with RYSTIGGO.14
Yes. Concomitant medications were permitted during the clinical study. At baseline in each treatment group (RYSTIGGO 7 mg/kg or 10 mg/kg or placebo), over 83% of patients were taking AChE inhibitors, over 56% of patients were taking steroids, and ~50% of patients were taking NSISTs, at stable doses.3,14
AChE=acetylcholinesterase; MG=myasthenia gravis; NSISTs=non-steroidal immunosuppressive therapies.
RYSTIGGO is a once-weekly, subcutaneous infusion that is administered in a 6-week treatment cycle, with every cycle followed by an individualized break in treatment.14
RYSTIGGO is given once weekly by a healthcare professional in 6-week cycles, with every cycle followed by an individualized break in treatment. An individualized dosing schedule for subsequent cycles is based on the clinical evaluation of the patient.14
Yes. RYSTIGGO can be administered in the physician's office infusion suite, at independent infusion centers, via home infusion, or in the hospital outpatient department.
RYSTIGGO is given once-weekly in 6-week cycles, with every cycle followed by a break in treatment. An individualized dosing schedule for subsequent cycles is based on the clinical evaluation of each patient. In the RYSTIGGO clinical studies, 4 treatment cycles were initiated per year on average, with a range of 1 to 7 cycles.14
The safety of initiating subsequent cycles sooner than 9 weeks (63 days) from the start of the previous treatment cycle has not been established.14
RYSTIGGO is dosed based on the body weight of each individual patient.14
In a Phase 3 clinical study, 8% of patients treated with RYSTIGGO experienced infusion site reactions versus 3% on placebo. Local reactions at the administration site occurred within 1 to 3 days after the most recent RYSTIGGO infusion.3,14
RYSTIGGO is a once-weekly subcutaneous infusion administered in approximately 15 minutes once preparation is complete.14
Administration14
- Time of administration may vary by patient. Duration of infusion may be longer based on infusion flow rate and patient weight
- RYSTIGGO is intended to be infused in the lower right or lower left part of the abdomen below the navel
- Rotate infusion sites for subsequent administrations
- Do not infuse where the skin is tender, bruised, red, or hard. Avoid infusing into tattoos, scars, or stretch marks
Observation14
- Monitor patients during treatment with RYSTIGGO and for 15 minutes after completion for clinical signs and symptoms of hypersensitivity reactions. If a reaction occurs, discontinue administration of RYSTIGGO and institute appropriate measures if needed
- Dosing schedule for subsequent cycles is based on clinical evaluation for each patient. In clinical trials, hypersensitivity reactions occurred within 1 day to 2 weeks of administration. One patient discontinued RYSTIGGO due to a hypersensitivity reaction. Local reactions at the administration site occurred within 1 to 3 days after the most recent RYSTIGGO infusion
Yes. Patients need to be monitored during the infusion of RYSTIGGO and for 15 minutes after completion of treatment to assess for clinical signs and symptoms of hypersensitivity reactions.14
Start adult patients on RYSTIGGO by enrolling them in ONWARD™. This is a personalized support experience built to help patients through every step of the treatment process with RYSTIGGO. Patients enrolled in ONWARD will be paired with a dedicated, medically trained Care Coordinator who will provide tailored support based on each patient's unique needs.*†
To get started, download the Start Form to enroll or e-enroll with the online portal.
*ONWARD is provided as a service of UCB and is intended to support the appropriate use of UCB medicines. ONWARD may be amended or canceled at any time without notice. Some program and eligibility restrictions may apply.
†ONWARD does not provide medical advice and does not replace the care of the healthcare provider. Care Coordinators will refer patients to their healthcare provider for any treatment-related questions.
The Infusion Center Locator can help identify sites of care with the ability to administer RYSTIGGO and connect them with your appropriate patients based on their ZIP code location.
RYSTIGGO vials should be refrigerated at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light until the time of use. Do not freeze. Do not shake. If needed, vials may be stored at room temperature up to 77°F (25°C) for a single period of up to 30 days in the original carton to protect the vial from light. Once a vial has been stored at room temperature, it should not be returned to the refrigerator. The discard date is 30 days after removal of the vial from the refrigerator. Write the discard date in the space provided on the carton. Discard the vial if not used within 30 days or if the expiration date has passed, whichever occurs first.14
RYSTIGGO Support
Yes. The J-code for RYSTIGGO is J9333.
You can download helpful reference materials here, which contain information on required codes, sample claim forms, and coding and billing information for RYSTIGGO.
Patients enrolled in ONWARD have access to a dedicated, medically trained Care Coordinator to provide personalized support. In addition, patients can access tools and resources to start and continue treatment, get assistance reviewing insurance coverage and potential financial assistance options, and help on how to track symptoms.*†
*ONWARD is provided as a service of UCB and is intended to support the appropriate use of UCB medicines. ONWARD may be amended or canceled at any time without notice. Some program and eligibility restrictions may apply.
†ONWARD does not provide medical advice and does not replace the care of the healthcare provider. Care Coordinators will refer patients to their healthcare provider for any treatment-related questions.
Get downloadable resources to help your patients access RYSTIGGO. These resources include: How to Acquire RYSTIGGO, Guide to Writing a Letter of Medical Necessity, Fulfillment Resource Guide, Prior Authorization/Predetermination Checklist, Guide to Writing a Letter of Appeal, and a Coding and Billing Guide (J-code: J9333).
References:
- Gable KL, Guptill JT. Antagonism of the neonatal Fc receptor as an emerging treatment for myasthenia gravis. Front Immunol. 2020;10(3052):1-9. doi:10.3389/fimmu.2019.03052
- Wolfe GI, Ward ES, de Haard H, et al. IgG regulation through FcRn blocking: a novel mechanism for the treatment of myasthenia gravis. J Neurol Sci. 2021;430:1-10. doi:10.1016/j.jns.2021.118074
- Bril V, Drużdż A, Grosskreutz J, et al. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023;22(5):383-394. doi:10.1016/S1474-4422(23)00077-7
- Trouth AJ, Dabi A, Solieman N, et al. Myasthenia gravis: a review. Autoimmune Dis. 2012;2012:1-10. doi:10.1155/2012/874680
- Jackson K, Parthan A, Lauher-Charest M, et al. Understanding the symptom burden and impact of myasthenia gravis from the patient's perspective: a qualitative study. Neurol Ther. 2023;12(1):107-128. doi:10.1007/s40120-022-00408-x
- Gambino CM, Agnello L, Ciaccio AM, et al. Detection of antibodies against the acetylcholine receptor in patients with myasthenia gravis: a comparison of two enzyme immunoassays and a fixed cell-based assay. J Clin Med. 2023;12(14):4781. doi:10.3390/jcm12144781
- Rodolico C, Bonanno C, Toscano A, et al. MuSK-associated myasthenia gravis: clinical features and management. Front Neurol. 2020;11(660):1-5. doi:10.3389/fneur.2020.00660
- Vakrakou AG, Karachaliou E, Chroni E, et al. Immunotherapies in MuSK-positive myasthenia gravis; an IgG4 antibody-mediated disease. Front Immunol. 2023;14:1212757. doi:10.3389/fimmu.2023.1212757
- Morren JA, Li Y. Myasthenia gravis: frequently asked questions. Cleve Clin J Med. 2023;90(2):103-113. doi:10.3949/ccjm.90a.22017
- Nair SS, Jacob S. Novel immunotherapies for myasthenia gravis. Immunotargets Ther. 2023;12:25-45. doi:10.2147/ITT.S377056
- Mahic M, Bozorg AM, DeCourcy JJ, et al. Physician-reported perspectives on myasthenia gravis in the United States: a real-world survey. Neurol Ther. 2022;11(4):1535-1551. doi:10.1007/s40120-022-00383-3
- Uzawa A, Ozawa Y, Yasuda M, et al. Minimal symptom expression achievement over time in generalized myasthenia gravis. Acta Neurol Belg. 2023;123(3):979-982. doi:10.1007/ s13760-022-02162-1
- Muppidi S, Silvestri NJ, Tan R, et al. Utilization of MG-ADL in myasthenia gravis clinical research and care. Muscle Nerve. 2022;65(6):630-639. doi:10.1002/mus.27476
- RYSTIGGO [Prescribing Information]. Smyrna, GA: UCB, Inc.
- Smith B, Kiessling A, Lledo-Garcia R, et al. Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. MAbs. 2018;10(7):1111-1130. doi:10.1080/19420862.2018.1505464
- Regnault A, Morel T, de la Loge C, et al. Measuring overall severity of myasthenia gravis (MG): evidence for the added value of the MG Symptoms PRO. Neurol Ther. 2023:1-18. doi:10.1007/s40120-023-00464-x
- Cleanthous S, Mork AC, Regnault A, et al. Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease. Orphanet J Rare Dis. 2021;16(1):457. doi:10.1186/s13023-021-02064-0
- A study to evaluate rozanolixizumab in study participants with generalized myasthenia gravis. NCT04650854. Updated February 26, 2024. Accessed June 10, 2024. https://clinicaltrials.gov/study/NCT04650854
- A study to investigate the long-term safety, tolerability, and efficacy of rozanolixizumab in adult patients with generalized myasthenia gravis. Updated September 5, 2023. Accessed June 10, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04124965
- Data on file. UCB Inc., Smyrna, GA.
