Long-term effect of intravenous alfacalcidol on secondary hyperparathyroidism in uremic patients on hemodialysis

Uremic patients almost have secondary hyperplasia of the prarathyoid glands. Many clinical trials have demonstrated the benefit of treatment with active vitamin D metabolites. Intravenous preparations seem to be more effective. However, there is paucity of data regarding the effect of various medical therapeutic modalities in uremic patients with severe secondary hyperparathyroidism [HPT]. To evaluate the long-term efficacy of intravenous 1 a-hydroxycholecalciferol [alfacalcidol] treatment in severe secondary HPT, in uremic patients on regular hemodialysis [HD]. Patients and 20 uremic patients on regular HD and suffering from severe secondary HPT were treated by intravenous alfacalcidol after each HD session, thrice weekly, for a period of 2 years. Alfacalcidol doses were carefully titrated according to the biochemical values. The dialysate calcium concentration was set to 1 mmol/l and calcium carbonate tablets were given at doses modulated to guard against hypercalcemic episodes. Patients were subjected to baseline and follow up laboratory tests especially s. intact PTH, s. calcium, s. inorganic phosphorus and s. bone alkaline phosphatase, as well as imaging procedures includinggg U/S examination of the neck, thallium-technetium scintigraphy and plain radiographs of the skeleton. S. intact PTH showed a rebound increase, and reached a mean value comparable to the basesline on the long-term [P=0.895 at 24th month], after an initial response to alfacalcidol therapy. The s. iPTH response to treatment was also heterogeneous and showed no correlation with the given dose. 74% of patients had at least one clinical episode of hypercalcemia versus 65% for hyperphosphatemia. This resulted in limitation of the alfacalcidol dose. The parathyroid gland size at end of study was significantly inccreased compared to the baseline [P=0.042]. Long-term intravenous alfacalcidol pulse therapy was not effective in controlling severe secondary HPT in HD patients. It also failed to correct the increased parathyoid gland size

Rheumatoid arthritis: early induction of disease remission

To evaluate the efficacy of tumor necrosis factor-alpha [TNF-alpha] blockade as bridge-therapy combined with methotrexate [MTX] in induction of early remission in rheumatoid arthritis patients. Patients and Sixty six patients with rheumatoid arthritis with poor prognostic disease features were enrolled in the current study. All had moderate to severe disease activity with unsatisfactory response to disease modifying antirheumatic drugs [DMARDs] mono-therapy. Patients were randomized into 3 groups: Group 1 were the patients who received TNF-alpha blockade therapy in combination with methotrexate [MTX] for 6 weeks than they were maintained on MTX alone for 18 weeks, group 2 included patients who received MTX mono-therapy and patients in group 3 who received prednisolone according to micro-dose regimen with MTX. All patients underwent initial full clinical examination as well as laboratory investigations [baseline evaluation]. The following disease activity parameters were determined at baseline, 6 weeks and 24 weeks after being enrolled in the study: Global patieny's and global physician's assessment scores, patients's pain score, number of tender as well as swollen joints, Health assessment questionnaire, serum C-reactive protein, erythrocyte sedimentation rate as well as morning stiffness duration. Standard plain X-rays were carried out for both hands, wrists, ankles as well as the forefeet. Joint erosions were assessed according to Larsen's score. Induction of disease remission after the 1st 6 weeks of therapy occurred in 45.45%, 27.27%, 36.36% in group1, 2 and 3 respectively, reflecting the higher efficacy of TNF-alpha blockade therapy in induction of early disease remission. After 18 weeks of stopping TNF-alpha blockad and maintaining the patients of group1 on MTX [24 weeks from start of the study], the 3 study groups showed comparable disease control revealing the absence of superiority of TNF-alpha blockade therapy compared with prednisolone-MTX combination as well as MTX monotherapy. On the other hand radiological evaluation of joint damage showed comparable incidence of joint erosions in the 3 groups reflecting equal efficacy of the 3 treatment regimens in controlling joint destruction. In view of results of the current study it can be concluded that TNF-alpha blockade is an effective therapy in RA that can induce early disease remission, however, this induced remission was not associated with superior efficacy in protection of joint damage compared with MTX mono-therapy and combined MTX-steroid therapy