1. CYCLOPHOSPHAMIDE AND METHYLPREDNISOLONE AS AN ALTERNATIVE TREATMENT IN SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS
Tania Gabriela Hernández Mojica.
UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO

2. Degenerative, inflammatory and demyelinating disease of the CNS.
It is the most frequent cause of permanent disability in young adults worldwide.
Mean onset age of MS ranges from 28 to 31 years.
MS affects more women than men (ratio 1.4:1 to 2.3:1)
MULTIPLE SCLEROSIS
Ramagopalan SV, Sadovnick AD. Epidemiology of multiple sclerosis. Neurol Clin May;29(2):
Goodin DS. The epidemiology of multiple sclerosis: insights to disease pathogenesis. Handb Clin Neurol. 2014;122:
Alonso A, Hernán MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology. 2008;71(2):129.

3. MULTIPLE SCLEROSIS

4. MULTIPLE SCLEROSIS MODALITIES
Relapsing-remitting multiple sclerosis (RRMS): clearly defined relapses, no progression in between.
Secondary progressive multiple sclerosis (SPMS): constant progression of disability, eventually no relapses. The mean age of convertion is 40 to 49 years.
MULTIPLE SCLEROSIS MODALITIES
Esclerosis Múltiple España
Lublin FD, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014; 83:278
Goodin DS. The epidemiology of multiple sclerosis: insights to disease pathogenesis. Handb Clin Neurol. 2014;122: .

5. SPMS TREATMENT INTERFERON β1a
Low efficacy: it only halts progression of the disease in 28-30% of patients.
High cost: 20,000-30,000 mexican pesos/month (1,200-1,800 euro)
Minimum wage: 2100 mexican pesos/month (125 euro)
Low adherence to treatment: subcutaneus injection every other day.
SPMS TREATMENT

6. CYCLOPHOSPHAMIDE Alchilation and cross-bonding of nucleic acid chains
Adverse effects: nausea, vomiting, alopecia, infections, gonadal supression, menstrual irregularities, myelosupression, haemorragic cystitis.
CYCLOPHOSPHAMIDE
Díaz C. Mecanismo de acción de los fármacos inmunosupresores. Revista Chilena de Reumatología 2008; 24(2):73-88

7. To determine the eficacy and safety of cyclophosphamide in secondary progressive multiple sclerosis patients.
OBJECTIVE

8. EFICACY AND SAFETY Eficacy: slowing the progression of the disability.
EDSS: expanded disability status scale (1-10, considering piramidal functions, cerebellum, brain stem, sensitivity, bladder and bowel control, sight and cognition).
AAR (annualized relapse rate): relapses per year = 0.8
PI (progression index): EDSS points divided by years of evolution =
Safety: adverse effects
EFICACY AND SAFETY
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33:

9. We conducted a clinical, retrospective, longitudinal trial in the Demyelinating Diseases clinic of the National Institute of Neurology and Neurosurgery with patients seen between january 2002 and august 2014.
The sampling was consecutive for convenience.
Inclusion criteria:
Diagnosed SPMS
No disease modifying treatment or failure to treatment.
EDSS <7.5
METHODS

10. METHODS Signing of informed consent
Complete neurological and physical examination, calculation of EDSS, PI and ARR, and laboratory and imaging studies.
Administration of CPM IV 1gr + methylprednisolone IV 1 gr monthly for 6 months (6 applications)
Administration of CPM IV 1gr + MP IV 1 gr every other month for 6 months (3 applications)
Clinical and paraclinical follow-up every three months
Statistical analysis withs Wilcoxon’s test, considering statistically significant a value of p < 0.05
METHODS

11. RESULTS: DEMOGRAPHIC CHARACTERISTICS

12. RESULTS: EFICACY
p = 0.977
p = 0.007
p = 0.005

13. RESULTS: SAFETY

14. The difference in PI indicates a minor disability and the stabilization of the disease.
The difference in ARR translates in fewer relapses, higher quality of life, reducing health care costs and less sick days at work.
There was not statistical significant difference in disability, however, the clinical significance was evident.
No adverse effect put the life at stake, nor did they caused drop-outs from the trial.
There were no cases of haemorragic cystitis reported
DISCUSSION

15. Cyclophosphamide is an effective treatment for SPMS, reducing PI and ARR.
The EDSS mean remained the same. Considering the natural history of SPMS, we can affirm that it stabilized the progression of the disease.
Cyclophosphamide is safe to use, since the adverse effects were uncommon and mild.
Although cyclophosphamide is not considered a first-line treatment for SPMS, it is a good alternative for patients with limited resourses or lack of response to interferon therapy.
CONCLUSION