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Immunosuppression protocols

There are many protocols described in the literature for different immune-mediated diseases and it is essential that the regimen should be individualized with consideration of the animal’s weight, body condition, previous exposure/response to glucocorticoids and responsiveness once treatment has started. Three examples are provided here. It is vitally important that the diagnosis of immune-mediated disease is confirmed before undertaking any of these protocols.

Prednisolone 40 mg/m2 (or 2 mg/kg if <15 kg) p.o. q24h, with or without: - Azathioprine 2 mg/kg p.o. q24h - Ciclosporin 5 mg/kg p.o. q12h - Mycophenolate mofetil 8–10 mg/kg p.o. q12h

See Appendix I for safety and handling of chemotherapeutic agents.

Dexamethasone (0.4 mg/kg i.v. q24h) may be substituted for prednisolone if the patient is unable to tolerate oral medications. Mycophenolate mofetil (MMF) (7–10 mg/kg i.v. q12h) can be used where oral medication is not tolerated. Once patient is able to tolerate oral medications, then substitute prednisolone for dexamethasone and switch to oral dosing of mycophenolate mofetil (8 mg/kg p.o. q12h) or, if preferred, azathioprine at the above doses. A single dose of vincristine (0.02 mg/kg i.v.) may be used in cases of IMTP, as it is may increase platelet number but extent of its benefits are unclear. Dyserythropoiesis may be seen in such cases but is clinically insignificant.

: Clopidogrel 1–2 mg/kg per day is indicated for dogs with IMHA, with or without low molecular weight heparins (dalteparin 150–175 IU/kg q8h) if there is clinical evidence of thromboembolic disease. Discontinue on remission (or once the prednisolone is discontinued).

: Not required unless there is a documented infection or known risk of infection (e.g. previous endocarditis). Empirical treatment with doxycycline (10 mg/kg p.o. q24h) may be indicated pending tests for tick-borne diseases in dogs with a history of travel or known tick exposure.

: In general, not required. In cases with known or suspected GI bleeding (melaena, haematemesis), omeprazole (1 mg/kg p.o. or i.v. q12h) offers effective suppression of gastric acid secretion. The practice of administering ranitidine etc. to every animal receiving high doses of steroids is not necessary and likely ineffective.

If a mild relapse (e.g. a fall in PCV of <5% without any clinical signs of anaemia) occurs following documented remission, this may be treated by reinstigating the drug dosages used at the last visit when the patient was in remission. Severe relapses should be treated by reinstigation of induction doses of all drugs used initially. If this is ineffective, or if rescue is to be attempted during initial induction phase of treatment (due to progressive deterioration), then additional immunosuppressants may be added. In cases of poor disease control, three immunosuppressive drugs may be used concurrently, with a risk of opportunistic (fungal) infections. An infusion of immunoglobulin (0.5-1.0 g/kg i.v. over 6-8 hours) may be administered in dogs not responding to other forms of treatment, but clinical benefit is not proven. In the non-acute setting, or if long-term control is necessary in a patient that has previously failed all other orally administered drugs, then consider leflunomide (2 mg/kg p.o. q24h).

Principles for dose reduction: Consider reduction of the prednisolone dose as soon as clinical response is apparent (resolution of agglutination, spherocytosis, hyperbilirubinaemia/haemolysed plasma and the PCV is stable or increasing). Decrease the prednisolone dose by 25–33% every 2–3 weeks, depending on severity of side effects and if features of disease are well controlled. Expected overall duration of treatment is approximately 3–5 months provided there is no relapse.

Week Glucocorticoid Azathioprine/ MMF Immunosuppressant 3 (if used) GI protectants (if used)
Remission 1 mg/kg q24h UC UC UC
2 0.5 mg/kg q24h UC UC STOP
4 0.5 mg/kg every other day 50% dose reduction STOP  
6 0.25 mg/kg every other day UC    
8 STOP      
10   UC    
12   UC    
14   STOP    

UC = dose unchanged.

Haematology to be rechecked at each visit (including 4 and 8 weeks after cessation of therapy) and remission confirmed prior to each dose reduction. Liver parameters should be rechecked at remission and monthly if on azathioprine.

Prednisolone: 3-4 mg/kg p.o. q24h, with or without:

• Chlorambucil: >4 kg body weight, 2 mg p.o. q48h; <4 kg body weight, 2 mg p.o. q72h • Ciclosporin: 5 mg/kg p.o. q12h • Mycophenolic acid (MPA): 10 mg/kg p.o. q12h

• See Appendix I for safety and handling of chemotherapeutic agents. If the patient is unable to tolerate oral medications, then dexamethasone (0.6–1.0 mg/kg i.v. q24h) may be substituted for prednisolone and mycophenolate mofetil (MMF) (7–10 mg/kg i.v. q12h) may be substituted for mycophenolic acid.

: Avoid in cats as there is no evidence of a risk of thrombosis in cats with IMHA currently, and risk of side effects.

: Not required unless there is a documented infection or known risk of infection (e.g. previous endocarditis) or known exposure to ticks. Empirical treatment with doxycycline (10 mg/kg p.o. q24h) may be indicated pending tests for Mycoplasma spp.

: Not required unless GI bleeding has been diagnosed. Effective suppression of gastric acid production is then required. Current evidence suggests that only famotidine and omeprazole will provide this. The practice of administering ranitidine etc. to every animal receiving high doses of steroids is not necessary and likely ineffective.

See Protocol 1: Canine immune-mediated haemolytic anaemia and immune-mediated thrombocytopenia for details.

See Protocol 1: Canine immune-mediated haemolytic anaemia and immune-mediated thrombocytopenia for details.

(NB: reports of feline immune-mediated thrombocytopenia are too rare to provide a protocol for treatment, but it is likely that a similar approach should be adopted.)

Protocol 3: Steroid-responsive meningitisProtocol 3: Steroid-responsive meningitis

: Prednisolone: 2 mg/kg p.o. q24h (as single dose or divided) for 7-14 days. Dexamethasone (0.4 mg/kg i.v. q24h) may be substituted for prednisolone for the first 2 days if the patient is unable to tolerate oral medications.

: If remission is achieved, then 1 mg/kg p.o. q24h for 6 weeks followed by 0.5 mg/kg p.o. q24h for 6 weeks, followed by 0.5 mg/kg p.o. q48h for 6 weeks, followed by 0.5 mg/kg p.o. q72h for 6 weeks, then stop.

: In the event of a relapse during or after completion of the protocol (or if remission is not achieved), then 2 mg/kg p.o. q24h can be reinstigated (or continued if remission not achieved) for a further 2 weeks, and then continued as the 24-week remission protocol.

: Not required unless there is a documented infection, known risk of infection (e.g. previous endocarditis) or known exposure to ticks.

: In general, not required.

Fig_immunosuppression_protocols.png

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