A safety analysis of oral prednisone as a pretreatment for rituximab in rheumatoid arthritis.

The administration of 100 mg of methylprednisolone intravenously (IV) 1/2 h prior to rituximab decreases the incidence of acute infusion reactions (AIRs). However, this pretreatment adds considerable time and conveys potential risk. We performed an open-label prospective assessment of oral prednisone as a pretreatment to rituximab. This was a 26-week open-label trial of 40 mg of oral prednisone given 1/2 h prior to rituximab as a prophylaxis against AIRs in patients with rheumatoid arthritis (RA). The primary endpoint was AIRs in the first 24 h after their initial infusion. Secondary endpoints include AIRs during the 24 h following their second infusion and any adverse events experienced during the 26-week study; efficacy measures were also followed as secondary endpoints. Sixty-four subjects were screened, and 50 subjects qualified. Fourteen out of the 50 (28 %) subjects had AIRs within 24 h of their first infusion. There were four AIRs (8.3 %) within 24 h of their second infusion. One of day 0 AIRs required drug discontinuation (wheezing/bronchospasm). Forty out of 50 (80 %) subjects experienced an adverse event during the 26 weeks. There were three SAEs deemed not to be study-drug related. The DAS28 and HAQ-DI all improved significantly at weeks 8, 16, and 26 compared to baseline. Historical controls demonstrate that 27 % of RA subjects experience AIRs with their first rituximab infusion. Our data suggest a smaller dose of oral prednisone is an effective alternative to IV methylprednisolone as a pretreatment for rituximab in patients with RA.

Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial.

OBJECTIVE: Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are known triggers of reactive arthritis (ReA) and exist in a persistent metabolically active infection state in the synovium, suggesting that they may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a 6-month course of combination antibiotics is an effective treatment for patients with chronic Chlamydia-induced ReA. METHODS: This study was a 9-month, prospective, double-blind, triple-placebo trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia-induced ReA. Eligible patients had to be positive for C trachomatis or C pneumoniae by polymerase chain reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead of azithromycin; 2) azithromycin and rifampin plus placebo instead of doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin. The primary end point was the number of patients who improved by 20% or more in at least 4 of 6 variables without worsening in any 1 variable in both combination antibiotic groups combined and in the placebo group at month 6 compared with baseline. RESULTS: The primary end point was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results. Six of 27 patients (22%) randomized to combination antibiotics believed that their disease went into complete remission during the trial, whereas no patient in the placebo arm achieved remission. Significantly more patients in the active treatment group became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse events were mild, with no significant differences between the groups. CONCLUSION: These data suggest that a 6-month course of combination antibiotics is an effective treatment for chronic Chlamydia-induced ReA.

The effect of a low-carbohydrate diet on bone turnover.

INTRODUCTION: Low-carbohydrate diets have become popular as weight loss techniques. These diets are high in protein, saturated fats, and omega-6 fatty acids. They also lead to a ketogenic state. These factors could lead to increased bone turnover. This study was designed to see whether a low-carbohydrate diet would lead to increased bone turnover in humans. METHODS: Thirty patients (15 study subjects and 15 controls) were recruited for this 3-month study. The 15 patients on the diet were instructed to consume less than 20 g of carbohydrates per day for the 1st month and then less than 40 g per day for months 2 and 3. Control subjects had no restrictions on their diet. The primary end point was urinary N-telopeptide (UNTx) at 3 months. Secondary end points included UNTx at 1 month, bone-specific alkaline phosphatase (BSAP) at 1 month, bone turnover ratio (BSAP/UNTx) at 1 month, and weight loss. RESULTS: The mean UNTx in the study subjects increased by 1.6 [95% confidence interval (CI) +/-22.8] compared with an increase of 1.9 (95% CI +/-17.6) in the controls at 3 months (p=0.86). The mean UNTx decreased by 2.2 (95% CI +/-27.2) and 3.1 (95% CI +/-17.6) at 1 month in the dieters and controls, respectively (p=0.36). The mean BSAP decreased by 0.53 (95% CI +/-2.96) in the dieters and increased by 0.34 (95% CI +/-2.92) in the controls at 1 month (p=0.27). The bone turnover ratio increased by 0.08 (95% CI +/-0.81) in the dieters and by 0.05 (95% CI +/- 0.27) in the controls at 1 month (p=0.78). The dieters lost 6.39 kg versus 1.05 kg for the controls at 3 months (p=0.0008). CONCLUSIONS: Although the patients on the low-carbohydrate diet did lose significantly more weight than the controls did, the diet did not increase bone turnover markers compared with controls at any time point. Further, there was no significant change in the bone turnover ratio compared with controls.

Polymyalgia rheumatica and temporal arteritis with sacroiliitis and osteitis pubis.

Polymyalgia rheumatica (PMR) and temporal arteritis (TA) have been associated with a seronegative polyarthritis that can mimic rheumatoid arthritis. Sacroiliitis and osteitis pubis are most often encountered in the different types of spondyloarthropathy. However, sacroiliitis and osteitis pubis have rarely been described in patients with polymyalgia rheumatica and temporal arteritis. We present two patients, one with temporal arteritis and the other with polymyalgia rheumatica, who also had many features of a spondyloarthropathy, including sacroiliitis and osteitis pubis. In reviewing the literature, we found 30 other patients with a diagnosis of PMR who also had sacroiliitis and/or osteitis pubis. We propose that the inflammatory arthritis associated with polymyalgia rheumatica and temporal arteritis can involve the axial joints, resembling a spondyloarthropathy. It is important for the clinician to recognize that sacroiliitis and osteitis pubis have been associated with PMR and TA so that their radiographic presence does not dissuade the clinician from making the correct diagnosis.

Antinuclear antibody-negative, drug-induced lupus caused by lisinopril.

The clinical symptoms of drug-induced lupus (DIL) are similar to those of idiopathic systemic lupus erythematosus. The literature indicates that in patients with DIL, sera generally contain antinuclear antibodies (ANAs); however, ANA-negative DIL has been reported. The list of medications implicated as etiologic agents in DIL continues to grow. This list includes two different types of angiotensin-converting enzyme inhibitors--captopril and enalapril. We report the first case of DIL caused by lisinopril. Our patient had negative results on ANA testing and had histone antibodies (IgG anti-[H2A-H2B]-DNA) mirroring the disease course. Antibodies to the (H2A-H2B)-DNA complex are seen in more than 90% of patients with active DIL, excluding those with DIL due to hydralazine. Thus, it is important to recognize the clinical significance of IgG anti-(H2A-H2B)-DNA antibodies and that negative ANA test results do not preclude the diagnosis of DIL.

V2 regions of 16S ribosomal RNA used as a molecular marker for the species identification of streptococci in peripheral blood and synovial fluid from patients with psoriatic arthritis.

OBJECTIVE: To detect the 16S ribosomal RNA (rRNA) of 3 streptococcal species in the peripheral blood and synovial fluid of patients with psoriatic arthritis (PsA). METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) detection targets bacterial 16S rRNA, which is present in bacteria at high copy numbers. The 3 species-specific primers for group A streptococci (GAS; Streptococcus pyogenes), group B streptococci (GBS; Streptococcus agalactiae), and Streptococcus pneumoniae were designed from the fragments of highly variable V2 regions of 16S rRNA. Total RNA was prepared from whole peripheral blood and joint fluid obtained from patients with PsA and rheumatoid arthritis (RA). All positive PCR reactions were then sequenced with a Pharmacia ALF DNA sequencing system. RESULTS: Our data in 19 PsA patients showed that 7 peripheral blood samples were positive for GAS (P = 0.006 versus GAS-positive RA patients [n = 0], by Fisher's exact test), and 2 were also positive for GBS. One synovial fluid sample from a PsA patient was positive for GAS. S pneumoniae was absent from all specimens. Seventeen patients with RA were PCR negative for the 3 streptococcal species. Peripheral blood from a patient with inflammatory bowel disease was positive for GAS. CONCLUSION: The presence of GAS 16S rRNA in the peripheral blood and synovial fluid of patients with PsA supports the concept that PsA is a reactive arthritis to certain streptococci.

Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veterans Affairs Cooperative Study.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy. METHODS: Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments. RESULTS: While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients.

Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy. METHODS: Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.

Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome). A Department of Veterans Affairs Cooperative Study.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy. METHODS: One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA.