PUBLIC CONSULTATION 2017 – Sjogren’s syndrome
2017 (v3.0) Proposed changes to v2.1 of the Criteria for the clinical use of intravenous immunoglobulin in Australia
v2.1 CONDITION NAME: Sjogren’s syndrome /v3.0 CONDITION NAME: Sjogren’s syndrome associated neuropathy /
PROPOSED APPROACH:
To retain Sjogren’s syndrome associated neuropathy in Exceptional circumstances only with the changes as outlined. / SUMMARY OF RATIONALE:
The recommendation is supported by factors including that:
- Neurological manifestations in Sjogren’s syndrome are rare, and the only indication for Ig therapy for patients with Sjogren’s syndrome is neuropathy. There are a number of neuropathy subtypes which can occur including:
- sensory ataxic neuropathy,
- painful sensory neuropathy without ataxia,
- multiple mononeuropathies,
- cranial neuropathies including trigeminal neuropathy and
- autonomic neuropathy.
- While the evidence base for use of Ig in this condition is weak, some response has been reported in small case series of patients with some forms of sensory neuropathy.
- Approximately 20 patients have received maintenance therapy nationally over the last 2 years, and it is understood that some are receiving demonstrable benefit from this treatment that is being regularly assessed.
- Alternative, more effective therapies are available for vasculitic neuropathy. As such, this neuropathy subtype is excluded.
- It is proposed to formally consult with Australian and New Zealand Association of Neurologists (ANZAN), Australasian Society for Clinical Immunology & Allergy (ASCIA) and the Australian Rheumatology Association (ARA) regarding the proposed criteria during the Public Consultation period. As a result, these proposed criteria may change.
-
- Sjogren’s neuropathy is not listed in the Guidelines for IVIg use in Canada (Ontario Regional Blood Coordinating Network, 2016), or the United Kingdom (UK Department of Health, 2011). /
v2.1 CONDITION CATEGORY: Condition for which Ig use is in exceptional circumstances only (Chapter 7)
v3.0 CONDITION CATEGORY: Condition for which Ig use is in exceptional circumstances only (Chapter 7) /
Role of Ig therapy: Multiple treatments have been trialled for treatment of Sjogren’s syndrome associated neuropathy, with corticosteroids in association with immunosuppressant medications demonstrating the best outcomes. However, where patients are refractory to or unable to tolerate first-line therapy, Ig has been reported to be effective in a few patient series with a variety of neuropathy subtypes and in one study, the majority successfully achieved a 30% reduction in steroid therapy dose (Rist, 2011).
The exact mechanism of action of Ig in the context of Sjogren’s syndrome associated sensory neuropathy is unknown. /
ITEM / CRITERIA v2.1 / PROPOSED REVISIONS TO THE CRITERIA / SPECIALIST WORKING GROUP RATIONALE FOR ADDITIONS/CLARIFICATIONS /
Condition Name / Sjögren’s syndrome / Sjogren’s syndrome associated neuropathy / Condition name revised to more appropriately reflect the specific diagnosis where evidence suggests some benefit of Ig therapy and is consistent with use in exceptional circumstances.
Specialty / Immunology / Neurology / The specialty is more appropriately Neurology given that the indication for Ig therapy will only be for Sjogren’s syndrome associated neuopathy and not other manifestations of Sjogren’s disease
Category / Exceptional circumstances only / Exceptional circumstances only / Unchanged
Specific Conditions / Sjögren’s syndrome / · Small fibre neuropathy
· Autonomic neuropathy
· Sensory neuropathy/neuronopathy / Relevant specific conditions are defined to support data analysis
Level of Evidence / Insufficient data (Category 4a) / Insufficient data (Category 4a) / Unchanged
Justification for Evidence Category / Sjogren’s syndrome associated neuropathy comprises a heterogeneous group of neuropathies. There is a very low level of evidence for IVIg use in this condition, with conflicting reports of efficacy. Improvement has been reported in small case series of patients with some forms of sensory neuropathy (Pereira 2016, Rist 2011, Yamashita 2013). Conflicting reports exist for patients with ataxic sensory neuronopathy, with one study reporting benefit (Takahashi 2003) but most studies (Rist 2011, Pereira 2016) and clinical experience suggesting it is ineffective for this patient group.
Approximately twenty patients have received maintenance therapy nationally over the last five years, and it is understood that some are receiving demonstrable benefit from this treatment that is being regularly assessed. The Specialist Working Groups (Immunology and Neurology) of the Immunoglobulin Governance Program recommend to retain the condition within the Criteria as an interim measure, in order to better understand the exact nature of the clinical benefit and collect data on the existing patients. However, if no demonstrable benefit can be identified, patients will not be eligible to remain on Ig therapy under these criteria. / This section has been developed following consultation of recent literature and by SWG consensus. It is proposed to formally consult with Australian and New Zealand Association of Neurologists, ASCIA and the Australian Rheumatology Association regarding the proposed criteria during the Public Consultation period.
Indications / Severe, primary Sjogren’s syndrome associated neuropathy that is unresponsive to corticosteroid and immunosuppressant therapy.
Relapse of Sjogren’s syndrome associated neuropathy within six months of trial off Ig therapy / Two indications have been developed, the second to manage treatment of responding patients that relapse on a trial of weaning from Ig therapy.
Description and Diagnostic Criteria / IVIg may be indicated in patients with some forms of neuropathy associated with Sjogren’s syndrome that is not caused by necrotising vasculitis where other treatments have not been effective. / Script developed to reflect the limitation of Ig therapy to patients with autonomic, small fibre or sensory neuropathy/neuronopathy.
Diagnosis is required / Yes / By which specialty / Clinical Immunology
Neurology
Rheumatology / Patients are most likely to be treated by any of the listed specialists.
Diagnosis must be verified / No / By which specialty
Exclusion Criteria / Sjogren’s syndrome associated vasculitic neuropathy / Vasculitic neuropathy in association with Sjogren’s syndrome is excluded as there is no evidence of benefit and alternative treatments are available.
Qualifying Criteria / Severe, primary Sjogren’s syndrome associated neuropathy that is unresponsive to corticosteroid and immunosuppressant therapy.
· Primary Sjogren’s syndrome with proven sensory or autonomic neuropathy
AND
· Significant disability due to neuropathy as measured by Modified Rankin Score (MRS) of at least 4 points
AND
· No response to an appropriate trial of corticosteroids
OR
· Corticosteroids are contraindicated
AND
· No response to at least one immunosuppressant agent
OR
· Immunosuppressant medication is contraindicated.
Relapse of Sjogren’s syndrome associated neuropathy within six months of trial off Ig therapy
· Deterioration of neuropathy (formally assessed) and Modified Rankin Score (by at least one point) in a previously stable patient as compared to the previous review score
AND
· Relapse occurs within six months of the last immunoglobulin dose / Qualifying criteria have been developed and evidence items will capture the type of neuropathy (proven diagnosis) and the formal method of assessment that will be used to measure the clinical response and level of neuropathy at qualifying (and that will be applied for comparison at the initial and continuing reviews).
The types of assessment methods expected to be used in new and existing patients include clinical examination together with investigations including nerve conduction studies, nerve biopsy, skin biopsy (IENFD), quantitative sensory testing, autonomic function tests or gastric emptying studies.
It is recognised that a Modified Rankin Score (MRS) is an insensitive scale for measurement of disability in this condition and alternative methods will be considered during the consultation process. If the MRS is used, a drop down menu will display a description of the rating levels.
The immunosuppressant agents might include:
i. Cyclophosphamide
ii. Azathiaprine
iii. Chlorambucil
iv. Methotraxate
v. Cyclosporin
vi. Rituximab
Previously responding patients are eligible to recommence Ig therapy if they relapse within 6 months of a trial of weaning.
Review Criteria / Severe, primary Sjogren’s syndrome associated neuropathy that is unresponsive to corticosteroid and immunosuppressant therapy.
IVIg should be used for a maximum period of four months (induction plus 3 maintenance cycles) before determining whether the patient has responded. If there is no benefit after this treatment, IVIg therapy should be abandoned.
Review by a Neurologist, Rheumatologist or Clinical Immunologist is required within 4 months of treatment to determine whether the patient has responded, and annually thereafter.
Documentation of clinical effectiveness is necessary for continuation of IVIg therapy.
On review of the initial authorisation period
Clinical effectiveness of Ig therapy can be demonstrated by:
· Improvement of neuropathy (formally assessed) compared to the qualifying assessment
AND
· Improvement in disability as measured by a decrease of at least 1 point or no deterioration in the Modified Rankin Score compared to the qualifying assessment
On review of a continuing authorisation period
For stable patients on maintenance treatment, review by a Neurologist, Rheumatologist or Clinical Immunologist is required at least annually.
Clinical effectiveness of Ig therapy can be demonstrated by:
· Improvement in or stabilisation of neuropathy (formally assessed) compared to the previous review assessment
AND
· Improvement in or stabilisation of the degree of disability as measured by the Modified Rankin Score compared to the previous review assessment
AND
· A trial of Ig weaning should be attempted after a year of therapy unless there is a contraindication to doing so.
Relapse of Sjogren’s syndrome associated neuropathy within six months of trial off Ig therapy
IVIg should be used for a maximum period of four months (induction plus 3 maintenance cycles) before determining whether the patient has responded. If there is no benefit after this treatment, IVIg therapy should be abandoned.
Review by a Neurologist, Rheumatologist or Clinical Immunologist is required within 4 months of treatment to determine whether the patient has responded, and annually thereafter.
Documentation of clinical effectiveness is necessary for continuation of IVIg therapy.
Once a patient has relapsed when trialled off Ig treatment, a second line immunomodulatory agent should be strongly considered as additional therapy.
IVIg should be used for a maximum period of four months (induction plus 3 maintenance cycles) before determining whether the patient has responded. If there is no benefit after this treatment, IVIg therapy should be abandoned.
Review by a Neurologist, Rheumatologist or Clinical Immunologist is required within 4 months of treatment to determine whether the patient has responded, and annually thereafter.
Documentation of clinical effectiveness is necessary for continuation of IVIg therapy.
On review of the initial authorisation period
Clinical effectiveness of Ig therapy can be demonstrated by:
· Improvement of neuropathy (formally assessed) compared to the qualifying assessment
AND
· Improvement in disability as measured by a decrease of at least 1 point or no deterioration in the Modified Rankin Score compared to the qualifying assessment
On review of a continuing authorisation period
For stable patients on maintenance treatment, review by a Neurologist, Rheumatologist or Clinical Immunologist is required at least annually.
Clinical effectiveness of Ig therapy can be demonstrated by:
· Improvement in or stabilisation of neuropathy (formally assessed) compared to the previous review assessment
AND
· Improvement in or stabilisation of the degree of disability as measured by the Modified Rankin Score compared to the previous review assessment
AND
· A trial of Ig weaning should be attempted after two years of therapy in patients that have previously relapsed after an earlier trial of withdrawal of IVIg, unless there is a contraindication to doing so.
Once a patient has relapsed in the first six months of a trial off therapy, a further trial might be considered after at least two years. / Review criteria have been developed by SWG consensus.
Clinical review of patients will require documentation of the assessment method and a description of the improvement after at least 4 months of Ig therapy.
A text description of the improvement in disability will be captured. It is recognised that the Modified Rankin Score may not be sufficiently sensitive to measure a change.
A text description of the improvement in disability will be captured. It is recognised that the Modified Rankin Score may not be sufficiently sensitive to measure a change.
A trial of weaning should be undertaken after 12 months treatment in most patients.
If a patient relapses following a trial of weaning, a second line immunosuppressant agent is recommended as additional therapy.
The formal assessment method being used to assess response is required to be documented together with the improvement in symptoms following Ig therapy.
A text description of the improvement in disability will be captured. It is recognised that the Modified Rankin Score may not be sufficiently sensitive to measure a change.
Two years after relapse, a trial of weaning from Ig therapy should be commenced in most patients.
Dose / Severe, primary Sjogren’s syndrome associated neuropathy that is unresponsive to corticosteroid and immunosuppressant therapy.
Induction Dose – 1- 2 g/kg in 2-5 divided doses
Maintenance Dose – 0.4 -1 g/kg, 4-6 weekly. The amount per dose should be titrated to the individual’s response. A maximum dose of 1 g/kg may be given in any 4 week period. This might be small doses more frequently than fortnightly.
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
Refer to the current product information sheet for further information on dose, administration and contraindications.
Relapse of Sjogren’s syndrome associated neuropathy within six months of trial off Ig therapy
Induction Dose – 1- 2 g/kg in 2-5 divided doses
Maintenance Dose – 0.4 -1 g/kg, 4-6 weekly. The amount per dose should be titrated to the individual’s response. A maximum dose of 1 g/kg may be given in any 4 week period. This might be small doses more frequently than fortnightly.
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
Refer to the current product information sheet for further information on dose, administration and contraindications / Dosing has been developed by consultation of the literature and by SWG consensus. Some flexibility in dosing has been supported to enable weaning from Ig therapy.
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PUBLIC CONSULTATION 2017 – Sjogren’s syndrome
References(most recent update: February 2016)
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http://www.clinexprheumatol.org/abstract.asp?a=5938
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https://www.ncbi.nlm.nih.gov/pubmed/19168191
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902517/
Rist S, Sellam J, Hachulla E, et al (2011) Experience of intravenous immunoglobulin therapy in neuropathy associated with primary Sjogren’s syndrome: A national, multicentric retrospective study. Arthritis Care Res, 63(9):1339-1344.
https://www.ncbi.nlm.nih.gov/pubmed/21584943
Takahashi Y, Takata T, Hoshino M, et al (2003) Benefit of IVIg for long-standing ataxic sensory neuronopathy with Sjogren’s syndrome. Neurology, 60:503-505.
https://www.ncbi.nlm.nih.gov/pubmed/12578938
Wakasugi D, Kato T, Gono T, et al (2009) Extreme efficacy of intravenous immunoglobulin therapy for severe burning pain in a patient with small fiber neuropathy associated with primary Sjogren’s syndrome. Mod Rheumatol, 19: 437-440.
https://www.ncbi.nlm.nih.gov/pubmed/19458906
Smith A, Jackson M, Wang F, et al (2005) Neutralisation of muscarinic receptor autoantibodies by intravenous immunoglobulin in Sjögren’s syndrome, Human Immunology, 66(4):411–6.
UK Department of Health (2011) Clinical Guidelines for Immunoglobulin Use: Second Edition Update. Available at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/216671/dh_131107.pdf
UK Department of Health (2011) Clinical Guidelines for Immunoglobulin Use: Second Edition Update: Summary Poster. Available at: https://www.igd.nhs.uk/wp-content/uploads/2016/04/DemandManagementPoster_v4_February2016.pdf
Yamashita H, Ueda Y, Ozaki T, et al (2013) Diagnosis and treatment of primary Sjogren Syndrome-associated peripheral neuropathy: a six-case series. Modern Rheumatology, 23:925.
http://link.springer.com/article/10.1007/s10165-012-0767-x
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