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November 14th, 2003
Experts recommend the use of IVIG in the treatment of blistering diseases
Consensus Statement
A multinational collaborative group of specialist physicians has recently produced a Consensus Statement on the use of intravenous immunoglobulins in the treatment of autoimmune mucocutaneous blistering diseases (AMBDs).
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| Pemphigus Vulgaris |
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Although rare, this group of diseases including: pemphigus vulgaris, bullous pemphigoid, cicatricial pemphigoid and epidermolysis bullosa acquisita, can cause serious sequalae that significantly diminish quality of life and may even cause death.
Conventional Therapy
Until recently, such conditions have only been treated with long-term systemic corticosteroids and / or immunosuppressive agents. Although these drugs may be effective in some patients, it is well recognised that they have numerous side-effects, some of which may be irreversible.
Serious side-effects
Adverse-effects of long-term corticosteroids such as prednisone include:
Immune suppression, severe infection, diabetes mellitus, osteoporosis, bone fractures, cataracts, glaucoma, hypertension and psychological disturbances.
Similarly, immunosuppressant agents such as cyclophosphamide, cyclosporine and azathioprine have a number of common but serious side effects. These include: bone marrow suppression, bacterial sepsis, hypertension, renal failure, hyperlipidemia, haemorrhagic cystitis, bladder cancer, lymphomas, skin cancers and infertility.
With conventional therapy, mortality from AMBDs ranges from 5-30%. Opportunistic infections, secondary to prolonged immune suppression, are frequently the cause of death. In pemphigus vulgaris, fewer than 30% of patients ever achieve a sustained medication free remission.
IVIG - an important addition to therapeutic options?
Given the clear limitations of conventional therapy, some physicians have started to use intravenous immunoglobulin for the management of such diseases, and have reported a number of successful outcomes.
Although the number of case reports and publications are growing, there have been few high quality randomised, double-blind, multi-center studies performed in AMBDs.
As such, the choice of optimal therapy is frequently controversial.
Reviewing the evidence
Recognising the dilemma facing clinicians, a Consensus Development Group was convened to critically evaluate the current published data on the use of IVIG therapy in AMBDs. Participants in this group included dermatologists, immunologists, ophtalmologists and oral medicine specialists.
Following their review of the literature the Consensus Development Group has produced guidelines which recommend the use of IVIG for AMBD´s in the following circumstances:
| INDICATION |
DEFINITION / COMMENTS |
| Failure of conventional therapy |
Failure to respond to 60mg/day (or 1mg/kg/ day) prednisone for 6 weeks with concurrent immune suppressant agent |
| Significant adverse effects from conventional therapy |
Any potentially life-threatening effect that may cause morbidity, mortality or interferes with activities of daily living |
| Contraindications to conventional therapy |
Any absolute or relative contraindications |
| Progressive disease |
When disease is progressing despite maximum conventional therapy |
| Uncontrolled rapid debilitating progressive disease |
When conventional therapy is unable to control disease |
| Rapid progressive epidermolysis bullosa acquisita |
With or without multiple mucosal involvement |
| Age of patient & pregnancy |
These factors do not contraindicate the use of IVIG |
The Consensus Group suggest that a dose of 2g / kg per cycle is most likely to produce the desired results in AMBDs. Initially, a cycle frequency of every three to four weeks is suggested for most patients. In aggressive disease such as ocular cicatricial pemphigoid, infusions every 2 weeks may be more appropriate.
Once effective control of the disease has been obtained, a reduction in either the dose or the frequency of infusions may be attempted. A suggested approach is to taper IVIG treatment by maintaining the dose but gradually increasing the time interval between infusions i.e. from 4 to 6, 8,10,12,14 and 16 weeks. The proposed end point is 2 infusions given 16 weeks apart.
Remission is defined as the cessation of all systemic therapy and the absence of clinical disease.
The Consensus Development Group pointed out that there are few side-effects associated with the use of IVIG (<1%) and those that do occur are usually mild and self-limiting.
All IVIG´s are not created equal
The Group also noted that although there are no comparative studies among the various commercial immunoglobulin preparations – there are differences and these may affect both the efficacy and safety of therapy:
Safety & Efficacy
They advised the selection of products that include complementary state-of-the-art viral inactivation steps that do not affect the integrity or biological activity of the molecule. An intact IgG molecule is important for efficacy of the product and therefore it is recommended that prescribers select IVIG preparations that employ fewer precipitation steps in their manufacture and avoid the use of those preparations that undergo proteolytic enzyme treatments.
Convenience
Liquid products offer the advantage of ready to use convenience, whereas powder preparations require time-consuming reconstitution.
Tolerability
Other important differentiating features include IgA content, and osmolarity as well as sugar and sodium content of the finished preparation. The use of sucrose as an IVIG stabiliser has been associated with significant adverse renal events including death.
Conclusions
The Consensus Development Group concluded that IVIG therapy represents a potentially important addition to the therapeutic options available to treat AMBDs. However, they suggest that a multicentre trial be undertaken to provide additional objective data on a larger cohort of patients.
The full Consensus Statement was published in the August 2003 edition of the Archives of Dermatology (Vol 139 pages 1051-1059). An abstract of this can be obtained by clicking here.
Please note that clicking this link will take you outside of the Octapharma homepage.
Further information on the use of IVIG in dermatology and Octapharma´s IVIG preparation - Octagam® can be obtained from Peter Schulte International Business Manager (Immunoglobulins)
© Octapharma AG, 2003
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