H. Malin Prupas

OBJECTIVE: To assess safety and clinical outcomes in patients with inflammatory arthritis after intraarticular (IA) injection of rAAV2-TNFR:Fc, a recombinant adeno-associated viral vector containing the human tumor necrosis factor (TNF) receptor-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) gene. METHODS: In this phase 1/2 randomized study, adults with persistent moderate or severe inflammation in a target joint, being treated with or without systemic anti-TNF therapy, received a single IA injection of either rAAV2-TNFR:Fc (1 x 10(11), 1 x 10(12), or 1 x 10(13) DNase-resistant particles/ml joint volume) or placebo, followed by open-label rAAV2-TNFR:Fc 12-30 weeks later, depending on when the target joint met predetermined criteria for reinjection. RESULTS: 127 subjects received the first injection of blinded study drug; 95 subjects received open-label rAAV2-TNFR:Fc. Administration site reactions, consisting of transient mild to moderate increases in tenderness and swelling of the injected joint, occurred after 23/191 (12%) rAAV2-TNFR:Fc injections and were dose-dependent. Rates of other adverse events were not dose-dependent. Notable serious adverse events (SAE) included culture-negative septic arthritis in a subject receiving leflunomide and fatal disseminated histoplasmosis considered unrelated to rAAV2-TNFR:Fc in a subject receiving adalimumab. In the phase 2 portion of the study, a 30% decrease in target joint global visual analog scale was observed in 21/50 (42%) rAAV2-TNFR:Fc subjects and 3/16 (19%) placebo subjects 12 weeks after first injection (p = 0.14). CONCLUSION: IA rAAV2-TNFR:Fc resulted in administration site reactions after 12% of injections. A fatal SAE, disseminated histoplasmosis, was considered not related to study agent. Patient-reported outcome measures of clinical response showed greater improvement in treated patients than placebo patients.

OBJECTIVE: To compare the clinical efficacy, effect on serum C-reactive protein (CRP), serum amyloid A (SAA), and plasma interleukin-6 (IL-6) levels, and safety of tenidap with a combination of hydroxychloroquine-plus-piroxicam, and piroxicam alone, in the treatment of rheumatoid arthritis (RA) patients. METHODS: A double-blind, randomized, multicenter study in which patients with active RA were treated with tenidap 120 mg/day, hydroxychloroquine 400 mg/day and piroxicam 20 mg/day, or piroxicam alone 20 mg/day, for 24 weeks. RESULTS: At weeks 12 and 24, tenidap produced greater improvements than piroxicam based on 5 primary efficacy parameters; this improvement showed statistical significance in 4 of the 5 measures at week 12, and in 3 of the 5 measures at week 24. Clinical improvements in the hydroxychloroquine-plus-piroxicam-treated with tenidap. Compared with piroxicam, tenidap was associated with significantly greater reductions in serum CRP concentrations at 4, 12, and 24 weeks, and significantly greater reductions in SAA concentrations at weeks 12 and 24. The decrease in SAA concentrations was also significantly greater at weeks 4 and 24 in the tenidap-treated group than in the hydroxychloroquine-plus-piroxicam-treated group. Significant reductions in plasma IL-6 levels were observed at weeks 4, 12, and 24 within the tenidap group, and at week 24 within the hydroxychloroquine-plus-piroxicam-treated group. The overall occurrence of side effects, including gastrointestinal side effects, was similar in all 3 treatment groups. A small proportion of tenidap-treated patients (6.4%) manifested mild, nonprogressive, reversible proteinuria of presumed renal proximal tubular origin, and 3-4% of patients had elevated transaminase levels. CONCLUSION: In the treatment of patients with RA, tenidap is as effective as the combination of hydroxychloroquine-plus-piroxicam, and is more effective than piroxicam alone; moreover, tenidap's safety profile is comparable to that observed with piroxicam alone, and with hydroxychloroquine-plus-piroxicam. The clinical response observed in this study, as well as the prompt decreases in acute-phase protein levels of CRP and SAA, and in plasma IL-6 levels, suggest that tenidap represents a new type of antiarthritic medication, with properties similar to, but not identical to, a therapeutic combination of a nonsteroidal antiinflammatory drug with disease-modifying antirheumatic drugs.

Abstract An unusual complication of tonsillectomy is tissue emphysema and/or pneumomediastinitis. A patient is described with both of these conditions, which probably resulted directly from the introduction of air into the tonsillar bed either during the surgical procedure itself or in the postoperative recovery period. The possible etiologies and recognition of this problem are discussed.

Six patients with systemic lupus erythematosus and avascular necrosis of the femoral head were treated by total hip arthroplasty (THA). The primary indication for surgery was persistent hip pain despite conservative therapy. Postoperatively, pain was relieved with corresponding improvement in range of motion in all six patients. There were no serious complications. At follow-up ranging from 23 to 76 months after surgery there was no recurrence of hip pain. These results suggest that THA is indicated in selected SLE patients.

ADMINISTRATION OF THIAZIDE DIURETICS has been re- ported to produce various idiosyncratic reactions in- cluding skin rash,' urticaria, photosensitivity,' jaundice, necrotizing vasculitis' and bone marrow depression.- There have been six reported cases of idiosyncratic pulmonary edema reactions immediately following the ingestion of hydrochlorothiazide.8-12These previously reported cases have not been associated with bone mar- row depression.We report a case of hydrochlorothiazide-induced acute pulmonary edema and associated severe leukopenia and thrombocytopenia in a patient shortly after she ingested a single 50-mg tablet of hydrochlorothiazide.