chlortetracycline and Arthritis--Rheumatoid

To determine the potential clinical efficacy of combination antibiotic therapy in treating rheumatoid arthritis (RA).. Twenty-one patients with active RA despite second-line treatment were randomized to receive either combination antibiotic therapy (treatment group, n = 11) or no additional therapy (control group, n = 10). Antibiotic therapy was given for 12 months and comprised oral tetracycline 250 mg twice daily, 3 times per week, and intravenous clindamycin infused on 5 consecutive days (300, 300, 600, 600, and 900 mg) followed by weekly infusions of 900 mg for 3 weeks and then fortnightly infusions for the remainder of the 12 months. The primary outcome measure was the American College of Rheumatology 20% (ACR20) response at the end of the initial treatment period of 12 months.. Five patients in the treatment group (45%) achieved an ACR20 response at 1 year compared to none in the control group (p = 0.04). Eight patients in the treatment group and 1 in the control group had a greater than 20% improvement in tender joint count (p = 0.008). There were also significant differences between the groups in physician and patient global assessments. Nine patients in the treatment group completed the 6 months' followup; of these, 3 sustained the ACR20 response.. Combined antibiotic therapy with intravenous clindamycin and oral tetracycline may be useful in the management of active RA. A double-blind, placebo-controlled trial of therapy is justified.

Topics: Administration, Oral; Anti-Bacterial Agents; Arthritis, Rheumatoid; Chlortetracycline; Clindamycin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Health Status; Humans; Injections, Intravenous; Male; Middle Aged; Pilot Projects; Severity of Illness Index; Single-Blind Method; Surveys and Questionnaires; Treatment Outcome

Protein Arginine Deiminase 4 (PAD4) has emerged as a leading target for the development of a Rheumatoid Arthritis (RA) pharmaceutical. Herein, we describe the development of a novel screen for PAD4 inhibitors that is based on a PAD4-targeted Activity-Based Protein Profiling reagent, denoted Rhodamine-conjugated F-Amidine (RFA). This screen was validated by screening 10 Disease Modifying Anti-Rheumatic Drugs (DMARDs) and identified streptomycin, minocycline, and chlortetracycline as micromolar inhibitors of PAD4 activity.

Topics: Arthritis, Rheumatoid; Chlortetracycline; Combinatorial Chemistry Techniques; Enzyme Inhibitors; Fluorescent Dyes; Hydrolases; Minocycline; Models, Biological; Molecular Structure; Protein-Arginine Deiminase Type 4; Protein-Arginine Deiminases; Streptomycin; Tetracycline

Topics: Aminopyrine; Analgesics; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antipyretics; Antirheumatic Agents; Arthritis; Arthritis, Rheumatoid; Biomedical Research; Bronchopneumonia; Chloramphenicol; Chlortetracycline; Hodgkin Disease; Humans; Influenza, Human; Penicillins; Pharmacology; Pleurisy; Pneumonia; Streptomycin

Topics: Arthritis; Arthritis, Rheumatoid; Chlortetracycline; Humans; Rheumatic Diseases; Streptococcal Infections; Streptococcus

Topics: Arthritis; Arthritis, Rheumatoid; Chlortetracycline; Humans; Joints; Pleasure