PURPOSE OF REVIEW: Since the introduction of biologic therapies into the 
treatment paradigm of rheumatoid arthritis (RA), there has been hope that oral 
small molecule immune modulators would be developed that would have a 
risk : benefit profile at least similar to biologic therapies, be more 
convenient for the patient and, hopefully, be less expensive. This article 
reviews the progress made in the development of these compounds over the past 
year.
RECENT FINDINGS: Additional information has become available in the past year on 
five oral compounds including kinase inhibitors (tofacitinib, fostamatinib, 
VX-509), an S1P lyase inhibitor (LX 3305) and a chemokine receptor-1 antagonist 
(CCX354-C). Efficacy has been shown in phase III with tofacitinib and in phase 
II with fostamatinib and VX-509; safety was the primary endpoint of the trials 
of CCX354-C and LX3305. Regarding side effects, liver test elevation and 
neutropenia occurred with tofacitinib, VX-509 and fostamatinib; lipid elevation 
with tofacitinib and VX-509; creatinine elevation and anemia with tofacitinib, 
and hypertension and diarrhea with fostamatinib.
SUMMARY: Compounds that inhibit tyrosine kinase pathways involved in cellular 
signalling have been shown to be effective in the treatment of RA with a 
reasonable risk : benefit ratio. It is too early to tell about inhibitors of 
other pathways.