LAS VEGAS – Corticosteroids remain the initial treatment of choice for myositis and myositis-associated interstitial lung disease, but immunosuppressive agents, intravenous immunoglobulin, and biologics can also play a role in the treatment of one or both of these conditions, according to Dr. Chester V. Oddis.
For myositis in general, Dr. Oddis, professor of medicine and associate director of the rheumatology fellowship training program at the University of Pittsburgh, recommends an initial divided dose of 30 mg of prednisone twice daily, continued until serum creatine kinase (CK) levels fall to normal. At that time, the total daily prednisone dose can be consolidated into a single morning dose, he said at Perspectives in Rheumatic Diseases 2013.
The prednisone can then be tapered by 25% every 3-4 weeks down to a 5- to 10-mg daily maintenance dose that is continued until active disease is suppressed for 12 months. This is a general guideline that helps prevent disease flares, he noted.
Keep in mind that improvement in strength generally lags behind improvement in CK levels, he added.
Nonsteroidal immunosuppressives
Not all patients will need an additional immunosuppressive agent, but for those who do, methotrexate is a good option, Dr. Oddis said, noting that methotrexate is the drug he is most comfortable using in those cases.
The literature also supports the combined use of methotrexate and azathioprine, which when given together have been shown to be effective in treatment-resistant myositis and in those who failed either of the drugs alone.
Dr. Chester Oddis
"So that’s a regimen you might want to think about," he said.
Another immunosuppressive option is mycophenolate mofetil (MMF), which has been shown in several small studies and case series to be of benefit. In one study, 6 of 10 patients with dermatomyositis successfully tapered corticosteroids with MMF, and 10 of 12 in another study experienced improvement in cutaneous features of the disease.
The use of intravenous immunoglobulin (IVIg) as add-on therapy with MMF was effective in severe refractory patients, including four with polymyositis and three with dermatomyositis. In a retrospective review of 50 patients with juvenile dermatomyositis, MMF for 12 months was well tolerated, improved skin and muscle, and proved to be steroid-sparing, Dr. Oddis said.
Cyclosporine, tacrolimus, and cyclophosphamide are other immunosuppressive options.
While cyclophosphamide is more often used for myositis-associated interstitial lung disease (ILD), it can be of benefit for refractory skin disease, and can be useful in non-ILD myositis cases that involve severe skin disease.
The only available controlled data for IVIg alone are from a study published more than 20 years ago, but that randomized, double-blind, placebo-controlled study showed that treatment was safe, effective, and steroid sparing in 15 patients with dermatomyositis, he said.
Biologics
As for biologics, anti–tumor necrosis factor–alpha (anti-TNF-alpha) therapy and B-cell therapy have both been considered. Anti-TNF-alpha therapy makes sense because TNF-alpha and other proinflammatory cytokines are increased in muscle tissue of myositis patients; TNF-alpha is toxic to myofibers and prevents their regeneration; and TNF-alpha enhances other inflammatory cytokines in both dermatomyositis and polymyositis, but data are lacking on whether targeting TNF-alpha is worthwhile.
B cell therapy, on the other hand, is showing promise. In one open-label pilot study, rituximab was effective in seven patients with refractory dermatomyositis, and in others it was effective in anti-synthetase syndrome. Rituximab also was effective in two studies for refractory myositis and dermatomyositis rash, and it induced longstanding remission in some of the patients. In another study, however, rituximab was not effective for dermatomyositis rash.
The multicenter Rituximab in Myositis (RIM) study, the largest ever done in myositis, evaluated rituximab for the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis patients.
Although the primary and secondary endpoints of the RIM study were not achieved, 83% of refractory adult and juvenile myositis patients met the definition of improvement, there was a significant corticosteroid sparing effect between the baseline dose and the dose at study conclusion, and treatment was generally well tolerated, he said.
Other targets that are being explored include interleukin-6 and type 1 IFN genes. Findings suggest that coordinated dysregulation of type 1 IFN signaling and IL-6 production are contributors to dermatomyositis pathogenesis, he explained.
Treating myositis patients with ILD
The treatment approach to these patients is somewhat similar to those without ILD, with corticosteroids as initial treatment, Dr. Oddis said.
Cyclophosphamide and azathioprine have been used early on, and also in corticosteroid resistant cases, but with variable results. Cyclophosphamide can be given orally or by IV for 3-6 months.
MMF has been used with success in connective tissue disease–associated ILD, and based on small studies it appears to be effective in myositis-associated ILD as well.