Effectiveness of a third tumor necrosis factor-α-blocking agent compared with rituximab after failure of 2 TNF-blocking agents in rheumatoid arthritis.

OBJECTIVE: To compare the effectiveness of a third tumor necrosis factor-α (TNF-α)-blocking agent with rituximab after failure of 2 TNF-blocking agents in patients with rheumatoid arthritis (RA) in daily clinical practice. METHODS: Patients receiving a third TNF-blocking agent or rituximab after failure of 2 TNF-blocking agents were selected from a Dutch biologic registry. The primary outcome was the results from the Disease Activity Score of 28 joints (DAS28) over the first 12 months after start of the third biologic using mixed-model analyses. Secondary outcomes included the course of the Health Assessment Questionnaire (HAQ) and the separate components of the DAS28 over the first 12 months and the change from baseline in DAS28 and HAQ at 3 and 6 months. RESULTS: The overall course of the DAS28 over the first 12 months was significantly better for rituximab (p = 0.0044), as also observed for the HAQ, although the latter results were not statistically significant (p = 0.0537). The erythrocyte sedimentation rates, C-reactive protein, and swollen joint counts showed a better course for rituximab (p = 0.0008, p = 0.0287, p = 0.0547, respectively), but not the tender joint counts or visual analog scale for general health. DAS28 decreased significantly in both groups at 3 and 6 months (p ≤ 0.024), but the change in HAQ was significant for rituximab only at 3 months (p = 0.009). CONCLUSION: During the first 12 months of therapy, a larger improvement in disease activity and a trend toward a larger decrease in functional disability was observed in patients receiving rituximab. Switching to a biologic with another mechanism of action might be more effective after failure of 2 TNF-blocking agents in RA.

Rituximab treatment in patients with refractory inflammatory myopathies.

OBJECTIVE: To assess the efficacy of rituximab on disease activity and muscle strength in patients with inflammatory myopathies refractory to conventional therapy. METHODS; Thirteen patients were treated with rituximab 1000 mg i.v., twice, with a 2-week interval and followed for a median of 27 months. Primary outcomes were disease activity measured by creatine phosphokinase (CPK), lactate dehydrogenase (LDH) levels and muscle strength measured by hand-held dynamometry and manual muscle testing (MMT). Secondary outcomes were improvement in secondary laboratory measures, global assessment of general health, disease activity and pain, CS dose, functional ability, health-related quality of life and safety. Retreatment with rituximab was conducted if disease activity relapsed. RESULTS; The median levels of CPK and LDH were significantly reduced by 93.2 and 39.8%, respectively, compared with baseline after 34.6 months. The median muscle strength measured by hand-held dynamometry was significantly improved by 21.5% after 24 months. The median increase in muscle strength measured with MMT was 7.0% after 24 months of follow-up, although this did not reach statistical significance. Secondary outcomes improved as well. CONCLUSION; Rituximab is an effective treatment in refractory inflammatory myopathies, showing a decrease in CPK and LDH, an increase in muscle strength and improvement in scores of disease activity, general health, functional ability and health related quality of life with sustained effect during a median of 27.1 months of follow-up.

Novel autoantibody markers for early and seronegative rheumatoid arthritis.

Approximately one-third of rheumatoid arthritis (RA) patients are seronegative for the 2 serological RA markers, rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (ACCP). Moreover, the sensitivities of both markers are lower in the diagnostically important early disease phase. The aim of this study was to identify additional autoantibody markers for early RA and for RF-negative, ACCP-negative (seronegative) RA. We screened an RA synovium cDNA phage display library with autoantibodies in plasma from 10 early (symptoms of maximum 1 year) and 10 seronegative (RF-negative, ACCP-negative) RA patients with validation in 72 additional RA patients and 121 controls (38 healthy controls, 43 patients with other inflammatory rheumatic diseases, 20 osteoarthritis patients and 20 subjects with mechanical joint complaints). Fourteen novel autoantibodies were identified that showed a 54% sensitivity and 90% specificity for RA. For 11 of these autoantibodies, an exclusive presence was demonstrated in RA patients (100% specificity, 37% sensitivity) as compared to controls. All early RA patients were positive for at least one of the identified autoantibodies and antibody-positivity was associated with a shorter disease duration (P = 0.0087). 52% of RA patients who initially tested negative for RF and ACCP, tested positive for at least one of the 14 novel autoantibodies, resulting in a 19% increase in sensitivity compared to current serological testing. Moreover, 5 identified autoantibodies were detected more frequently in seronegative RA patients, indicating that these autoantibodies constitute novel candidate markers for this RA subtype. We demonstrated that the targets of 3 of these 5 autoantibodies had an increased expression in RA synovial tissue compared to control synovial tissue, pointing towards a biological rationale for these auto antibody targets in RA. In conclusion, we identified novel candidate autoantibody markers for RA that can be detected in early and seronegative RA patients indicating the potential added value for RA diagnostics.

Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab.

OBJECTIVE: For patients with rheumatoid arthritis (RA), yearly influenza vaccination is recommended. However, its efficacy in patients treated with rituximab is unknown. The objectives of this study were to investigate the efficacy of influenza vaccination in RA patients treated with rituximab and to investigate the duration of the possible suppression of the humoral immune response following rituximab treatment. We also undertook to assess the safety of influenza vaccination and the effects of previous influenza vaccination. METHODS: Trivalent influenza subunit vaccine was administered to 23 RA patients who had received rituximab (4-8 weeks after rituximab for 11 patients [the early rituximab subgroup] and 6-10 months after rituximab for 12 patients [the late rituximab subgroup]), 20 RA patients receiving methotrexate (MTX), and 29 healthy controls. Levels of antibodies against the 3 vaccine strains were measured before and 28 days after vaccination using hemagglutination inhibition assay. The Disease Activity Score in 28 joints (DAS28) was used to assess RA activity. RESULTS: Following vaccination, geometric mean titers (GMTs) of antiinfluenza antibodies significantly increased for all influenza strains in the MTX-treated group and in healthy controls, but for no strains in the rituximab-treated group. However, in the late rituximab subgroup, a rise in GMT for the A/H3N2 and A/H1N1 strains was demonstrated, in the absence of a repopulation of CD19+ cells at the time of vaccination. Seroconversion and seroprotection occurred less often in the rituximab-treated group than in the MTX-treated group for the A/H3N2 and A/H1N1 strains, while seroprotection occurred less often in the rituximab-treated group than in the healthy controls for the A/H1N1 strain. Compared with unvaccinated patients in the rituximab-treated group, previously vaccinated patients in the rituximab-treated group had higher pre- and postvaccination GMTs for the A/H1N1 strain. The DAS28 did not change after vaccination. CONCLUSION: Rituximab reduces humoral responses following influenza vaccination in RA patients, with a modestly restored response 6-10 months after rituximab administration. Previous influenza vaccination in rituximab-treated patients increases pre- and postvaccination titers. RA activity was not influenced.

The reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent does not influence the effect of a second TNF blocking agent in patients with rheumatoid arthritis.

OBJECTIVE: To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent. METHODS: Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking agents. Patients were divided into 3 groups based on reason for discontinuation of the first: nonresponse, loss of response, or adverse events. The primary outcome was the change from baseline of the disease activity (by DAS28) at 6 months, corrected for the baseline DAS28 score. Secondary outcomes were the change from baseline at 3 months, EULAR response rates, and the percentages of patients who reached a DAS28 score < or = 3.2 at 3 and at 6 months. RESULTS: In total, 49 patients who failed due to nonresponse, 75 due to loss of response, and 73 due to adverse events were included. At 6 months, the change of DAS28 score from baseline did not differ significantly between the groups (-0.6 to -1.3; p > or = 0.173) and similar good and moderate response rates were found (12% to 18%, p > or = 0.523, and 34% to 55%, p > or = 0.078, respectively). The secondary outcomes were also comparable between the 3 groups. CONCLUSION: The results of our observational study suggest that a second TNF blocking agent may be effective after failure of the first, regardless of the reason for discontinuation of the first TNF blocking agent.

Surgical treatment for the vulvar vestibulitis syndrome.

OBJECTIVE: To study the outcome and complications of surgical treatment for vulvar vestibulitis syndrome and to identify patient characteristics that may have influenced the outcome. METHODS: Relevant patient characteristics were extracted retrospectively from the medical records of 155 women aged 40 years or younger who had received surgical treatment for vulvar vestibulitis syndrome. To assess outcome and complications, 126 of these 155 women (81%) participated in a telephone interview, conducted 1 to 4 years after surgery. RESULTS: After surgery 93% of the patients could have sexual intercourse compared with 78% before surgery; this increase was statistically significant (Mantel-Haenszel odds ratio 3.43, 95% confidence interval [CI] 1.48-7.96). In 62% of the women (95% CI 53-70%), sexual intercourse was painless after surgery. Eighty-nine percent (95% CI 84-95%) would recommend surgical treatment to other women experiencing vulvar vestibulitis syndrome. There were no major complications. Decreased lubrication during sexual arousal was the most frequently reported adverse effect (24%, 95% CI 16-32%), followed by the development of a Bartholin's cyst (6%, 95% CI 2-10%). More of the women aged 30 years or younger reported that they could have sexual intercourse after surgery, and more of them would recommend surgical treatment to other patients than women aged 31 years or older. CONCLUSION: Surgical treatment for vulvar vestibulitis syndrome achieved high success rates with an acceptable rate of complications. Age of 30 years or younger was associated with a better outcome. LEVEL OF EVIDENCE: III.