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Rituximab might have edge on conventional treatment of myasthenia gravis
Will Boggs MD
NEW YORK (Reuters Health) - Rituximab appears to outperform conventional immunosuppressive therapy in patients with myasthenia gravis, especially those with new-onset disease, according to a retrospective study.
“I was not so surprised to see that rituximab seemingly worked better in new-onset compared to refractory disease,” Dr. Fredrik Piehl of Karolinska University Hospital and Karolinska Institutet, in Stockholm, told Reuters Health by email. “What was more surprising was that conventional treatments performed so poorly over time; these patients had much higher rates of relapses, need of rescue therapies, but also switched therapies due to problems with tolerability.”
Rituximab, a B-cell-depleting monoclonal antibody approved for treating B-cell lymphoma, rheumatoid arthritis and systemic vasculitis, has shown encouraging results in patients with refractory myasthenia gravis.
Dr. Piehl and colleagues compared outcomes with rituximab versus conventional immunosuppressants in new-onset generalized myasthenia gravis (gMG) patients who lacked muscle-specific tyrosine kinase (MuSK) antibodies and compared outcomes with rituximab started early or late after disease onset.
The study included 72 patients who received rituximab (24 with new-onset disease, 34 with treatment-refractory disease, and 14 treated the first time more than 12 months after disease onset) and 26 patients with new-onset disease received conventional treatment.
During a mean follow-up of 97 months, 55 rituximab-treated patients achieved clinical remission. Time to remission was significantly shorter in the new-onset group (seven months) than in the refractory patients (16 months), the researchers report in JAMA Neurology.
Shorter time from onset of generalized disease to initiation of rituximab therapy was the only significant predictor of attaining remission.
At six months after rituximab treatment, CD19+ B-cell counts were below the detection limit in 53% of patients, were below 30 million/L in 28% and were greater than 30 million/L in 19%. But there was no clear association between attaining remission or time to remission and B-cell counts before the start of rituximab therapy, at the administration of the drug, or rituximab dose.
In the comparison of new-onset gMG patients, the proportion of patients in clinical remission at 12 and 24 months was significantly larger with rituximab (87% and 96%, respectively) than with conventional immunotherapies (58% and 62%).
Patients receiving rituximab went into clinical remission significantly faster than did patients receiving conventional immunotherapies (seven vs. 11 months), required fewer rescue therapies during the first 24 months of observation, and were tapered off immunomodulatory drugs more rapidly.
Only 3% of rituximab-treated patients discontinued treatment because of adverse events, compared with 46% of patients treated with conventional immunotherapies.
“In current treatment guidelines rituximab is mentioned as a possible third-line option, which based on our results might not be the best positioning of this agent,” Dr. Piehl said. “While these results have to be regarded as preliminary, they indicate that rituximab might be a promising therapy for those newly diagnosed with MG.”
“A significant proportion of patients with generalized MG continues to have symptoms fluctuating over time, affecting quality of life and necessitating regular medication,” he said. “In my opinion, we should consider efforts to treat with more effective therapies right from disease onset, which may curb more chronic changes to the immune system and thereby providing long-term benefits.”
Dr. Piehl added, “Here it is valuable to know that the effects we saw came with a low-dose protocol (one single 500-mg infusion, compared to the most frequently used protocol in MG of 4 weekly infusions of about 500 mg over a month), which certainly reduces costs, but potentially also improves safety.”
Dr. Raffi Topakian of Academic Teaching Hospital Wels-Grieskirchen, in Wels, Austria, who recently reported high efficacy of rituximab in myasthenia gravis, told Reuters Health by email, “Rituximab can be a powerful drug for MG: efficacious, safe, and relatively fast acting. Early treatment with rituximab should be considered: we, too, detected a signal that longer disease duration/late treatment with rituximab in patients with non-MuSK+ MG was associated with lower probability to achieve remission.”
“We give rituximab at low dose only due to safety concerns, as higher doses could lead to very prolonged B-cell depletion with issues regarding susceptibility to infections (think of COVID-19) and the timing of much-needed vaccinations,” he said.
Dr. Zaeem Siddiqi of the University of Alberta, in Edmonton, Canada, who recently reviewed myasthenia gravis therapies directed against B cells, told Reuters Health by email, “The study is timely, as the negative results reported from the recent phase-2 clinical trial in acetylcholine receptor antibody (AChR Ab)-positive MG (BeatMG) were surprising, as several large cases series had shown rituximab to be quite effective in MG, even in refractory disease.”
“In my opinion, the results of this study make a strong case for the use of rituximab earlier in the course of AChR Ab-positive MG, as currently done in patients with anti-MuSK MG, possibly as an initial steroid-sparing agent,” he said.
“Rituximab is more effective and tolerated better, has a convenient dosing regimen, i.e., every 6 months, lacks need for regular blood monitoring, and has a favorable side effect profile,” Dr. Siddiqi said. “The study results also provide further clarity on rituximab dosing, i.e., 500 mg every 6 months.”
The study had no commercial funding.
SOURCE: bit.ly/3fmp14i JAMA Neurology, online May 4, 2020.
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