Arundathi Jayatilleke, MD
Iguratimod (IGU) is a novel small-molecule synthetic DMARD being studied for RA; its exact mechanism is unknown, but it inhibits NF-kB activation and seems to reduce bone resorption via RANKL and cartilage erosion via matrix metalloproteinases. Currently, it is approved in Japan and China for treatment of RA; initial studies from 2008-2010 showed improved ACR20 rates compared to placebo and comparable rates with methotrexate monotherapy; combination therapy with methotrexate appears to be more effective than either methotrexate or IGU monotherapy. Yoshikawa et al present a small study of 47 patients receiving methotrexate or methotrexate with IGU and show promising results regarding tapering of methotrexate with sustained remission/low disease activity and decrease in ultrasound evidence of synovitis in patients receiving IGU, suggesting that it is a reasonable longer-term option for RA patients. However, the medication is not approved in the US, nor have studies in patients in the US been published, so generalizability in patients outside of Japan and China is uncertain, in addition to concerns related to the small sample size.
In contrast, tocilizumab is an established therapy for RA; Pappas et al present real-world clinical practice data from the Corrona RA registry. Among nearly 1800 RA patients who initiated tocilizumab therapy, the mean durability of response was over 3 years in terms of maintaining minimum clinically important difference (MCID) over baseline CDAI and over 1 year in terms of maintaining low disease activity. Most patients in the study had previously received biologic therapy. Though the observational nature of the study limits its generalizability, the addition of efficacy data to persistence on therapy lend weight to this evidence regarding durability of response to tocilizumab, as the proportion of patients maintaining MCID was >50% at 3 years.
Treatment options are limited for RA patients who have ILD or other pulmonary complications. The fear of causing or exacerbating pulmonary toxicity limits the use of methotrexate, leflunomide, and anti-TNF biologics. Some data support the safety of rituximab and abatacept. A retrospective observational study looked at outcomes in RA patients on rituximab and JAK inhibitors. Reassuringly, respiratory event rates were no different between the two groups though number of patients and trial design prevents wider generalization; it is also unknown whether RA-ILD improves with ritixumab or JAK-inhibition. However, given these results, studying JAK inhibitors in larger prospective studies would be reasonable.