KYOTO, Japan — Subcutaneous (SC) immunoglobulin offers several benefits compared with intravenous (IV) infusion as maintenance treatment for chronic inflammatory demyelinating polyneuropathy (CIDP), including medical, personal, and possibly financial advantages, a new study suggests.
IV immunoglobulin is an established treatment for CIDP, but infusions have to be administered by a healthcare professional whereas at-home treatment with SC immunoglobulin can offer increased autonomy, convenience, and quality of life for patients, as well as potential cost savings. The SC route may also provide more stable immunoglobulin levels.
However, weekly SC administration has not previously been studied in CIDP in an adequately powered randomized clinical trial with appropriate disability outcome measures, said Ivo van Schaik, MD, PhD, University of Amsterdam Academic Medical Center, the Netherlands, so the Polyneuropathy and Treatment with Hizentra (PATH) trial (NCT01545076) trial was designed for this purpose.
The results were presented here at the XXIII World Congress of Neurology.
This multicenter, international, double-blind, randomized, placebo-controlled trial enrolled adult patients with definite or probable CIDP between March 2012 and November 2015. Immunoglobulin treatment at study entry was withdrawn for up to 12 weeks to establish that patients were dependent on the treatment in order to keep the disease in check (ie, that they worsened without it). Those who were not immunoglobulin dependent were withdrawn from the study.
Patients shown to be immunoglobulin dependent were then restarted on IV immunoglobulin for up to 13 weeks to “restabilize” them. Those who achieved restabilization could stay in the trial. They were then randomly assigned to weekly placebo (n = 57) or to SC immunoglobulin (IgPro20 immune globulin SC 20% liquid; Hizentra, CSL Behring) at a low dose of 0.2 g/kg (n = 57) or a high dose of 0.4 g/kg (n = 58) for 24 weeks.
The primary endpoint of the trial was the proportion of patients with a CIDP relapse or who withdrew for any reason during 24 weeks of treatment. Relapse was defined as at least a 1-point drop in the Inflammatory Neuropathy Cause and Treatment (INCAT) score, which measures degree of arm and leg disabilities, on a 0 to 5 scale for upper or lower extremities, for a potential score of 0 to 10. Higher scores represent increased disability.
The primary endpoint scores showed that SC immunoglobulin reduced the number of relapses and withdrawals compared with placebo, and both doses also reduced the number of relapses alone compared with placebo. Both the 0.4-g/kg (P < .001) and the 0.2-g/kg (P = .007) doses were significantly better than placebo but were not significantly different than each other (P = .323).
Table. Primary Endpoint: Reduction in CIDP Relapse or Withdrawal for Any Reason
| Endpoint | Placebo (n = 57) | 0.2 g/kg SC Immunoglobulin (n = 57) | 0.4 g/kg SC Immunoglobulin (n = 58) |
|---|---|---|---|
| CIDP relapse or withdrawal for any reason (%) | 63 | 39 | 33 |
| CIDP relapse (%) | 56 | 33 | 19 |
The median INCAT score increased by 1 point between baseline and the end of the 24 weeks for the placebo group but did not change in either SC immunoglobulin group. Muscle strength on placebo worsened by 2 points on the 0 to 5 point Medical Research Council Scale for Muscle Strength. Again, both doses of SC immunoglobulin protected against deterioration.
Adverse events were somewhat higher in the SC immunoglobulin groups (52% to 58%) compared with the placebo group (37%), but they were largely mild to moderate, consisting of local infusion site reactions (placebo, 7.0%; low dose, 19.3%; high dose, 29.3%).
“There was no patient who had to stop because of those reactions,” Dr van Schaik said. “Also of note is that those reactions were very high at the beginning of the trial, during the first 8 infusions, and then quickly decreased as patients became used to this kind of therapy.”
When surveyed, most patients (88%) said they found the SC therapy “extremely” easy, “very” easy, easy, or “somewhat” easy to use.
“The data from this study support a weekly subcutaneous dose of 0.2 to 0.4 grams per kilogram,” Dr van Schaik said, with maintenance dosing individualized based on the patient disease situation and the previous IV dose and frequency.
When asked by Medscape Medical News how the efficacy of SC maintenance compares with IV dosing, he said the trial did not directly compare them, but he showed a back-up slide with data from PATH and a previous trial using IV immunoglobulin at 1 g/kg every 3 weeks.
Absolute risk reductions were very similar and even were slightly higher with high-dose SC immunoglobulin (24% risk reduction with low-dose and 37% risk reduction with high-dose SC immunoglobulin vs 29.4% with IV immunoglobulin). Also, the numbers needed to treat were similar: 4.2, 2.7, and 3.4, respectively.
Session chair, Katsuhisa Ogata, MD, National Higashisaitama Hospital, Hasuda, Saitama, Japan, commented to Medscape Medical News that he sees the results as supporting a new form of maintenance therapy for CIDP. He cautioned about the local infusion site reactions, but very few were more serious than mild to moderate.
“So I hope this therapy will be a very good option for maintenance therapy for CIDP,” he said. Right now, he said only IV immunoglobulin is approved in Japan for CIDP maintenance therapy, but he predicted that if SC immunoglobulin becomes available, “the patients will be very happy to be able [to use it for] good maintenance for CIDP.”
CSL Behring sponsored the PATH trial. Dr van Schaik is chair of the PATH steering committee for CSL Behring and has received departmental honoraria for serving on scientific advisory boards for CSL Behring, Baxter/Baxalta, and UCB. Dr Ogata has disclosed no relevant financial relationships.
XXIII World Congress of Neurology. Abstract 84. Presented September 17, 2017.
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