Second, low-dose-methotrexate (LD-MTX) intolerance was becoming a major problem above the 15 mg/week dose. From oncology colleagues, we learned that a moderate dose of GC prior to chemotherapy prevents nausea and other unpleasant sensations of chemotherapy. We started giving MP, varying from 4 to 16 mg weekly about 30 minutes before the LD-MTX dose. Whether it prevented or reduced LD-MTX intolerance was not studied systematically, but unexpectedly it was noted, on withdrawing the weekly MP dose, that several patients soon returned, complaining of increased pain and/or swelling in the joints. We then systematically analyzed patients who had been taken off the weekly MP dose. On reinitiating the weekly dose of MP, symptoms subsided quickly.
This work on 74 RA patients was presented at the annual meeting of the Indian Rheumatology Association in 2010.4 The patient group included 66 women (median age 49 years) with rheumatoid factor and ACPA positivity in 80% and 60%, respectively. The median disease duration was 76 months (range 19–300 months). They were under regular follow-up in the clinic. All of them were prescribed MP, varying from 4 to 16 mg/week, synchronized with LD-MTX weekly. The additional drugs included hydroxychloroquine, folic acid, calcium and vitamin D3. At the baseline, 60 patients (81%) had high or moderate disease activity (DAS28). In their follow-up, all the patients who had achieved remission or low disease activity state were advised to discontinue weekly MP doses. At that time, 65 patients (83.78%) were in remission, 12 patients (16.2%) were in low disease activity state and none had moderate or high disease activity. At follow-up after discontinuation of the weekly MP, 27 patients (36.49%) reported increased symptoms within a few weeks. Among them, 24 (88.8%) had objective joint swelling, with raised ESR and CRP in 13 (48%) and four (15%), respectively.
On reinitiating their original weekly MP dose, 21 patients (87.5%) again achieved remission or low disease activity. The three other patients required higher than their original weekly MP dose to achieve remission or low disease activity state. The routine monitoring for any adverse effects of this treatment, especially for markers of metabolic syndrome (e.g., blood glucose, lipid profile, hypertension) and DEXA-scans, did not show any significant change from the baseline levels.
I mentioned this work during my presentation at the 2013 ACR/ARHP Annual Meeting in San Diego with the warning that it was possibly based on a grade IV evidence and mostly experience and/or eminence (ACR Master observation) and should be used judiciously.5
