TNFi and Methotrexate Together or Not?

The common practice of tapering methotrexate doses in rheumatoid arthritis patients who also take tumor necrosis factor inhibitors (TNFi) does not adversely affect disease activity or long-term survival, according to a new observational study. Clinical guidelines recommend the addition of methotrexate to TNFi to improve the effectiveness of TNFi alone. However, half of rheumatoid arthritis patients experience discomfort from or are inconvenienced by adverse events due to methotrexate. When the combination of methotrexate and TNFi results in significant clinical improvement, some patients request to be tapered off or to discontinue methotrexate to avoid adverse events rather than to taper or discontinue TNFi.[[{"type":"media","view_mode":"media_crop","fid":"42433","attributes":{"alt":"©R.Badowski/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_2901176935993","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4593","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":" ","typeof":"foaf:Image"}}]] Dutch researchers explored how frequently methotrexate is tapered or discontinued in daily clinical practice and what effect this might have on disease activity and on TNFi drug survival. They analyzed data from the Dutch Rheumatoid Arthritis Monitoring registry on 1,331 patients who started their first TNFi. Treatment effectiveness after methotrexate tapering or discontinuation was analyzed using Disease Activity Score of 28 joints (DAS28). The results show that one-third of the patients had methotrexate tapering and 10% discontinued the drug. On average, DAS28 improved after tapering methotrexate and after stopping the drug at 6 and 12 months. About one-quarter of the patients in both the taper and discontinuation groups relapsed (DAS28 increase >0.6). There was no influence of tapering or discontinuation of methotrexate on long-term drug survival of TNFi. In fact, TNFi drug survival of the taper group tended to be better than that in the continuation group. "In daily practice, patients with rheumatoid arthritis do taper and discontinue their methotrexate dose. This does not seem to influence DAS28 over time or the long-term TNFi drug survival,” the researchers stated. They suggest that long-term drug survival is still better in the patients who taper methotrexate because the patients still use a low dose of methotrexate.  Another explanation may be that rheumatologists chose the right patients to taper or discontinue methotrexate, which may explain “the remarkable finding that DAS28 still decreases after tapering or stopping methotrexate.” Another possible explanation, they state, is that there is still some effect of the TNFi treatment, so the decrease in DAS28 is still due to the effect of the TNFi. The implication is perhaps some rheumatoid arthritis patients taking TNFi can reduce the discomfort/inconvenience of adverse events due to methotrexate and improve their quality of life. 

References:

Manders SHM, van de Laar MAFJ, et al.

"Tapering and discontinuation of methotrexate in patients with RA treated with TNF inhibitors: data from the DREAM registry,"

RMD Open

2015;1:e000147. doi:10.1136/rmdopen-2015-000147.