6 ID 1 2 3 4 5 6 7 ID 1 2 3 4 5 6 7 P value∗† †P value∗ Autism Research and Treatment Table 3: Language and autism behavior ratings over the course of the study for each study participant. Expressive Language Baseline Week 6 Week 12 0.0 0.0 0.0 1.0 1.0 2.0 85.0 67.0 76.0 38.0 36.0 38.0 35.0 46.0 0.0 59.0 65.0 1.00 na†† Receptive Language Baseline Week 6 Week 12 9.0 10.0 5.0 14.0 13.0 20.0 72.0 79.0 60.0 27.0 36.0 46.0 48.0 49.0 0.0 62.0 67.0 0.110 na†† Childhood Autism Rating Scale∗ Baseline Week 6 Week 12 51.0 51.0 51.0 44.0 43.0 43.0 33.0 30.0 27.0 42.0 41.5 39.0 35.0 33.0 39.5 39.5 33.5 0.043 0.109 ∗Decreasing scores reﬂect increased improvement. †P values represent the results of the diﬀerences between baseline values and 6 and 12-month values using the Wilcoxon Signed Ranks Test. ††Insuﬃcient data to compute. Table 4: Individual clinical global impression ratings over the 12-week study period. Language Expressive∗ Baseline Week 6 Week 12 7.0 6.0 6.0 7.0 6.5 6.0 4.0 1.5 2.0 5.0 5.0 4.0 4.0 3.0 3.0 6.0 4.0 5.0 2.0 0.042 0.023 Receptive Language∗ Baseline Week 6 Week 12 6.0 4.0 6.0 5.5 4.0 4.0 2.0 1.5 2.0 4.0 2.0 2.0 3.0 2.0 2.0 6.0 4.0 5.0 1.5 0.027 0.066 Baseline 7.0 4.0 4.0 4.0 5.0 5.0 Social Skills∗ Week 6 4.0 2.0 3.0 2.0 1.5 0.066 Week 12 4.0 4.0 1.0 2.0 4.0 0.066 ∗Decreasing scores reﬂect increased improvement. †P values represent the results of the diﬀerences between baseline values and 6 and 12-month values using the Wilcoxon Signed Ranks Test. weeks in all patients, so we felt the values were valid for analysis in this study—especially serum levels which reﬂected true baseline versus end of treatment changes. In addition, serum level values could be correlated to behavioral and language scoring. Consistent testing standards are necessary and timing of samples before true meaningful cytokine data in autism can be assessed in treatment protocols. Patients’ repeated exposure to the tests and developmen- tal maturation are potential limitations to the research ﬁnd- ings. Further, some patients completed neuropsychological testing after lab work, the medical appointment with the physician, and additional wait time, which led to behavior noncompliance that likely aﬀected test results. No patients suﬀered severe adverse reactions and all three patients who dropped out of study recovered fully from ANC levels and rashes. Despite the limitations, to our knowledge, this open-label study represents the ﬁrst attempt to treat autism by speciﬁ- cally targeting elevated innate inﬂammatory cytokine levels. Safety monitoring and pharmacokinetic data were success- fully completed during this pilot study and exploratory observations of clinical and cytokine changes suggest a trend towards improvement. Correlating treatment outcomes with cytokine level changes may be a target in future autism spectrum treatment, especially in those with known maternal or postnatal immunological risk factors. Larger blinded and placebo-controlled studies assessing cytokine measurement and cytokine-targeted treatment in autism patients with TNF-α or other inﬂammatory cytokine elevation are war- ranted. References [1] J. Baio, “Prevalence of autism spectrum disorders-autism and developmental disabilities monitoring network, 14 sites, United States, 2008,” MMWR Surveillance Summaries, vol. 61, no. 3, pp. 1–19, 2012. [2] American Psychological Association, Diagnostic and Statistical Manual of Mental Disorders, Skyscape, Washington, DC, USA, 4th edition, 1994. [3] P. T. Shattuck, “The contribution of diagnostic substitution to the growing administrative prevalence of autism in US special education,” Pediatrics, vol. 117, no. 4, pp. 1028–1037, 2006. [4] A. Cavagnaro, Autistic Spectrum Disorders: Changes in the Cal- ifornia Caseload An Update: June 1987–June 2007, Department of Developmental Services, Sacramento, Calif, USA. [5] L. A. Croen, J. K. Grether, J. Hoogstrate, and S. Selvin, “The changing prevalence of autism in california,” Journal of Autism and Developmental Disorders, vol. 32, no. 3, pp. 207–215, 2002. [6] M.I.N.D. Institute, Report to the Legislature on the Principle Findings from the Epidemiology of autism in California, Uni- versity of California, Davis, Sacramento, Calif, USA, 2002.