086 Clinical, investigational and treatment factors do not determine prognosis of patients with inflammatory neuropathies

IntroductionIdentifying patients who need long-term immunoglobulin (IVIg) treatment in patient with inflammatory neuropathies is essential as recent treatment trials show a remission rate of up to 40%.AimsCompare retrospective data on clinical, investigational and treatment factors in patients who have ceased IVIg with patients who have failed a cessation trial.Methods15 patients who successfully suspended IVIg infusions were compared with 15 in whom decreasing or stopping IVIg was unsuccessful.Results30 patients (12 with CIDP and 3 with MMN in both groups) were diagnosed 39.5 months from onset of symptoms in the successful group vs. 40.7 months in the unsuccessful group (p=0.953). There was a significant difference in the summed upper limb sensory amplitudes on electrophysiology prior to starting IVIg between the patients with CIDP (17.4 mV vs. 9.8mV p=0.007). There was no difference in the average doses between the groups. A successful cessation trial was attempted at a mean of 60.5 months post starting treatment, compared with 60 months in the unsuccessful patients.ConclusionThere is a need for objective biomarker to measure disease activity because other than one neurophysiology marker, other factors did not help predict a successful cessation trial of IVIg.

Relationship Between Polymorphisms in Methotrexate Pathway Genes and Outcome of Methotrexate Treatment in a Cohort of 119 Patients with Juvenile Idiopathic Arthritis

Objective.To identify clinical and pharmacogenetic determinants of efficacy and toxicity of methotrexate (MTX) in juvenile idiopathic arthritis (JIA) over time.Methods.A cohort of 119 consecutive patients with JIA treated with MTX was reviewed. The Juvenile Arthritis Disease Activity Score including 71 joints was used to measure disease activity. Nonresponders were patients who did not reach a minimum of 30% improvement after 6 months of treatment or were switched to biologic drugs in the first 6 months because of inefficacy. All adverse events (AE) were noted. Genotyping of single-nucleotide polymorphisms (SNP) in the genes coding for MTX transporters, folate pathway, and adenosine pathway was performed using real-time PCR methods. Univariate and multivariable penalized logistic and Cox regression were used to analyze data.Results.Thirty patients (25.8%) were defined as nonresponders and 55 (47.2%) were switched to biologics during the followup. Sixty-five patients (54.5%) reported AE in a total of 405 patient-years, and 10 patients (8.4%) discontinued MTX because of AE. AMPD1 rs17602729 and MTHFD1 rs2236225 were associated with gastrointestinal AE while the latter together with MTRR rs1801394 also demonstrated associations with developing hepatoxicity. MTHFR rs1801131, ABCG2 rs2231137, wild-type of MTR rs1805087, and wild-type of ABCC2 rs2273697 were identified as potential markers for discontinuing MTX treatment because of AE. MTHFR rs1801133, MTRR rs1801394, and ABCC2 rs2273697 were associated with switching to biologics.Conclusion.SNP in different MTX metabolic pathways influence treatment with MTX. Genetic variability is a better marker for toxicity than efficacy.