Treatment Options and Promising Research for Refractory Myositis Cases

Sometimes there may be loss of efficacy after a particular immunosuppressant agent, such as Imuran, has been used. There may have been a trigger to have caused your recent flare. I am glad to hear that you have now responded to the CellCept and IVIg.

I generally use caution with methotrexate if there is underlying ILD because of the incidence of pneumonitis as a possible side effect from methotrexate. That being said, if you have been on it for four years without any changes to your PFTs, then it is likely okay to continue it as long as your doctors are keeping track of your PFTs and lung imaging studies on a routine basis. We are limited in epidemiological studies that give us accurate numbers due to the rarity of inflammatory muscle disease. Overall incidence of IIM is 6-10 per million, but incidence of Jo-1-positive IIM may be 1.2-2.0 per million. Average age at diagnosis is 50 years (22-74 years). Predominantly female, 2:1 ratio, may be higher in some series. You can look to see if there are any recent epidemiological studies available. I do not know of a single reference source for patients available for antisynthetase syndrome, but there are many articles in the pulmonary and rheumatology literature.

I also use IVIg for treatment of necrotizing myopathy. There are different ways to prescribe the IVIg. For example, rheumatologists often dose the IVIg as 2 g/kg of ideal body weight split over two days once a month (so 2 infusions of 1 gram/kg for 2 consecutive days once monthly). Treatment durations (such as up to 3-6 months or longer) vary with response and tolerability. Some rheumatologists and neurologists use a dosing schedule of 0.4 g/kg of ideal body weight split over 3-5 consecutive days once monthly. We often start the IVIg at a very slow rate and gradually increase the rate pending tolerability. You are correct that infusion reactions can occur. An IgA will need to be obtained prior to prescribing IVIg, because up to 5% of the general population has an IgA deficiency, and if you have it and you receive a preparation with IgA antibodies, then reactions, including anaphylaxis (a severe allergic reaction), may occur. If there is an IgA deficiency detected, then IVIg preparations that do not have IgA in them are administered. Another common side effect is headache. We pre-treat often with acetaminophen and Benadryl. Sometimes IV steroids are given to reduce the incidence of infusion reactions.

Rituximab is an infusion (usually given as a dose of 1000 mg for two doses every six months) that may be helpful in the treatment of the rash and weakness from the inflammatory muscle disease. It suppresses your “B” cells and remains in your system for up to six months and sometimes longer. There is a high risk of infections including serious and atypical infections, so please speak to your doctor to see if this is the right medicine for you. You would need to be screened for TB prior to starting as well as hepatitis B, hepatitis C, and HIV. It also may cause an allergic and/or infusion reaction. Onset of action is about 2-3 months. If you are not responding to the methotrexate and prednisone, it is reasonable to consider rituximab if you do not have any contraindications to it.

I do not have much experience with using Acthar. It is recognized to have anti-inflammatory and immunomodulatory properties that may help to lower the dose of prednisone. Acthar has similar side effects to prednisone, including weight gain, acne, thin skin, depression, or mood disorder, hypertension and osteoporosis.

Patients with the SRP antibody often have a necrotizing myopathy that is refractory to standard immunosuppressive medications. There may be a higher incidence of swallowing difficulties (“dysphagia”) with SRP positive antibody and a higher incidence of heart involvement from the myopathy. We are limited by a lack of randomized, controlled studies to guide us about what is the most successful treatment for anti-SRP antibody patients, but I have prescribed methotrexate, CellCept, IVIg, and rituximab for treatment. Please look at the website, clinicaltrials.gov to see if there are any open trials recruiting patients who have SRP antibody.

If you are experiencing irregular heartbeats, ask your doctor about ordering a 24- or 48-hour Holter monitor to assess your heart rhythm. Necrotizing myopathy may affect the heart. If the echocardiogram is normal, but there remains a high suspicion for heart involvement from the myopathy, then a referral to a cardiologist may be appropriate. The cardiologist may do more advance testing, such as a cardiac MRI if there are no contraindications. IVIg may cause a racing heartbeat, but if it is the cause of it, then the racing or irregular heartbeat would occur during the infusions or right after the infusions. If you think that the IVIg is the cause, one way to tell is to stop the IVIg to see if the irregular heartbeats go away.

In general, high CK levels are reflective of active inflammatory muscle disease. However, if you have large muscle bulk, then the CK may register as higher than expected and may not necessarily mean active muscle disease. Additional testing for muscle disease activity may be appropriate to determine if the high CK is reflective of active muscle disease in your case, such as an MRI of the thighs or a test called an EMG.

Muscle cramping and burning sensations may be caused from active DM. Sometimes medications such as gabapentin (Neurontin) or pregabalin (Lyrica) are helpful for treatment of the burning and cramping pain. Please be aware that these medications have side effects such as sleepiness. These sensations may also be caused from neuropathies or certain vitamin deficiencies such as iron, vitamin D or vitamin B12. Please make sure that your doctor has checked for neuropathies and vitamin deficiencies. Regular physical therapy with routine calf or thigh muscle stretching is also helpful for alleviating the discomfort. Talk to your doctor about a referral if appropriate to a physical therapist.

Acthar is recognized as having anti-inflammatory and immunomodulatory properties. It stimulates the adrenal gland to make cortisol, so the glucocorticoids such as prednisone can be lowered. I do not have much experience with prescribing Acthar, although some of my colleagues use it with their patients. Side effects vary and are similar to the side effects of prednisone. Some side effects include but are not limited to the following: high blood pressure, fluid retention, weight gain, thin skin, easy bruising, acne, mood disorder such as depression, and osteoporosis. It also has been associated with a complication called “adrenal insufficiency” (when the adrenal glands get sluggish or stop working) if Acthar is used long-term. This complication requires the expertise of an endocrinologist to help with treatment if adrenal insufficiency occurs.

Some patients with PM/DM may have an “overlap” with another autoimmune disease, such as scleroderma, that puts them at higher risk for malabsorption and malnutrition because of slowed bowel transit and subsequent complications such as small bowel bacterial overgrowth. Difficulty swallowing (i.e. dysphagia) also may occur in active PM/DM due to inflammation in the pharyngeal (throat) muscles. If severe, it may lead to significant weight loss and possible malnutrition. Assessment of malabsorption and malnutrition requires the expertise of a gastroenterologist, so I ask them to assist in the work-up.

The CK levels may not always be an accurate reflection of inflammatory muscle disease if you have been on steroid and/or immunosuppressive treatment. Sometimes, I will get an MRI of the muscles to check for muscle inflammation and/or muscle damage. If you have low CK levels, then it may be because you have reduced muscle mass from chronic muscle damage. Guided physical therapy to build up your muscle tissue and core body strength is also very important to prevent falls; please make sure that you are doing physical therapy on a routine basis. Finally, ask your provider if you have been checked for inclusion body myositis. Sometimes, this muscle disease can be missed on a muscle biopsy due to sampling error but can lead to frequent falls. In inclusion body myositis, the CK is typically low such as in the 200s. Regarding the debilitating fatigue that you describe, it may not all be coming from polymyositis. I often see fatigue as a symptom of multiple causes such as endocrine disorders, non-restorative sleep habits, sleep apnea, pain syndromes, mood disorder, side effects of medications (particularly pain medications), or serious heart or lung diseases. Make sure that you have been checked for these disorders. Regarding CK levels and treatment success, it varies on the individual and the treatments used. In general, the higher the CK level, the more likely that treatment needs to be aggressive; as a result, the higher the likelihood of side effects.

A dermatologist is very helpful to ask about topical remedies for itchy scalp and darkened skin tone (i.e. hyperpigmentation). I have prescribed steroid shampoos, such as Clobetasol, for itchy scalp. I do not prescribe hormone replacement therapy for darkened skin, but a dermatologist would have more insight. Please consider asking your provider for a dermatology referral.

Rituximab is a medication that treats both inflammatory arthritis and inflammatory myositis. If you do not have any contraindications to receiving it (such as exposure to TB, hepatitis B, hepatitis C, or HIV), then it may be an option to explore. Keep in mind that you would have to stop the Orencia if it’s decided to choose rituximab. Also, keep in mind that rituximab is a biologic therapy; as with any biologic, there is a higher risk for infections, including serious and atypical infections. Ask your doctor if it is right for you.

I also prescribe IVIg and methotrexate for necrotizing myopathy. If your CK is significantly high and you are not responding, then your doctor may consider using a higher dose of IVIg and/or methotrexate if tolerated. Unfortunately, there are no controlled trials that guide us in choosing therapies after you have been on the “standard” medications to treat myopathy as you have listed above. Cyclosporine or tacrolimus may be effective, particularly if you have interstitial lung disease, but they also may result in significant side effects that require close monitoring by your providers. There are novel therapies currently under investigation such as tocilizumab and abatacept, but they are not used as standard of care of treatment of necrotizing myopathy at this time.

It depends. Sometimes, it is warranted to use steroids and several medications at once (such as combined with IVIg and methotrexate) if there are serious manifestations of dermatomyositis such as severe weakness, trouble swallowing, trouble breathing, or other serious organ complications. The more immunosuppressive medicines that are used at once and at higher doses, then the higher likelihood that side effects, drug interactions, or serious infections may occur. Other times, if the dermatomyositis is not as severe, a single drug may be effective. There is variability with respect to insurance companies approving certain drug therapies; often, I have to go through an appeal process to get them to approve certain therapies. You are correct that it may take up to 2-6 months for medications to work, so there may be a delay in finding a drug that works for you. You are not alone. This is frustrating to many patients.

It is unusual not to respond with improvement to the higher dose of prednisone after you have been on a daily dose of 7.5 mg. Ask your doctor to check your heart for pulmonary hypertension and to check your lungs for pulmonary fibrosis. Both can be complications of dermatomyositis. If your tests do not show these complications or any other serious organ complications, then ask your doctor to consider other therapies instead of methotrexate, such as mycophenolate mofetil (CellCept) or rituximab, as long as there are no contraindications to them and you have not had serious infections. These medications are also associated with increasing your risk for experiencing certain infections, including serious infections. Ask your doctor if either of these medications is right for you. These therapies take a couple of weeks to a couple of months to reach efficacy, so you may need to remain on a higher dose of prednisone for a while until either of them start working effectively.

The diagnosis of dermatomyositis requires at least four out of the of the following five elements: a rash typical of dermatomyositis (such as Gottron’s papules and/or heliotrope rash), elevated muscle enzymes, weakness of the proximal muscles, abnormal results on a test called an EMG showing myopathy, and a muscle biopsy. If you do not fulfill these requirements, then you may not have dermatomyositis, although certainly the Mi-2 antibody is seen in dermatomyositis. Ask your doctors to consider additional work-up for dermatomyositis such as a muscle biopsy if you have not had one (or another muscle biopsy if you already had one), or a referral to a neuromuscular specialist. The quality and intensity of the pain that you describe seems a bit atypical for dermatomyositis. Ask you doctors if you have been checked for other neurologic disorders such as large and/or small fiber neuropathy.