Treatment with high-dose recombinant human hyaluronidase-facilitated subcutaneous immune globulins in patients with juvenile dermatomyositis who are intolerant to intravenous immune globulins: a report of 5 cases.
BACKGROUND
High-dose intravenous immune globulins (IVIg) are frequently used in refractory juvenile dermatomyositis (JDM) but are often poorly tolerated. High-dose recombinant human hyaluronidase-facilitated subcutaneous immune globulins (fSCIg) allow the administration of much higher doses of immune globulins than conventional subcutaneous immune globulin therapy and may be an alternative to IVIg. The safety and efficacy of fSCIg therapy in JDM is unknown.


METHODS
In this retrospective case series, five patients with steroid-refractory severe JDM were treated with high-dose fSCIg due to IVIg adverse effects (severe headaches, nausea, vomiting, difficult venous access). Peak serum IgG levels, muscle enzymes, the childhood myositis assessment scale and adverse effects were retrieved for at least 6 months following intiation of fSCIg. Data were analyzed by descriptive statistics. Patients initially received fSCIg 1 g/kg every 14 days, resulting in median IgG peak levels of 1901 mg/dl (1606-2719 mg/dl), compared to median IgG peak and trough levels while previously receiving IVIg of 2741 mg/dl (2429-2849 mg/dl) and 1351 mg/dl (1156-1710 mg/dl). Additional antirheumatic therapies consisted of low-dose glucocorticoid therapy, methotrexate, mycophenolate mofetil and/or rituximab. Two patients maintained clinically inactive disease and three patients had only a partial treatment response. In the three patients with partial treatment response, fSCIg 1 g/kg was then given on days 1 and 6 of every 28-day cycle resulting in IgG peak levels of between 2300-2846 mg/dl (previously 1606-1901 mg/dl on the biweekly regimen), resulting in clinically inactive disease in two of the three patients. There were no relevant adverse effects that limited continuation of fSCIg treatment.


CONCLUSIONS
High-dose fSCIg is well-tolerated in patients with JDM and high peak serum IgG levels can be achieved which may be important for treatment success. High-dose fSCIg may therefore be an alternative to high-dose IVIg and deserves further study.


BACKGROUND
This is a case series and data were retrospectively registered.
Deutsches Zentrum für Kinder- und Jugendrheumatologie, Garmisch-Partenkirchen, Germany.
Fabian
F
Speth
Deutsches Zentrum für Kinder- und Jugendrheumatologie, Garmisch-Partenkirchen, Germany.
Johannes-Peter
JP
Haas
Klinik für Pädiatrische Rheumatologie und Immunologie, Universitätsklinikum Münster, Münster, Germany. claas.hinze@ukmuenster.de.
Claas H
http://orcid.org/0000-0001-9247-4729
CH
Hinze
D002463:Cell Membrane Permeability / Q000187:drug effects; D002648:Child; D003882:Dermatomyositis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage / Q000493:pharmacokinetics; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D056747:Immunomodulation; D008297:Male; D015166:Monitoring, Immunologic / Q000379:methods; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D011994:Recombinant Proteins; D006821:Hyaluronoglucosaminidase
Intravenous immune globulins; Juvenile dermatomyositis; Recombinant human hyaluronidase; Subcutaneous immune globulins