Objectives There is a need for effective and safe treatment during pregnancy in women with chronic inflammatory diseases. This study evaluated placental transfer of certolizumab pegol (CZP), an Fc-free anti-tumour necrosis factor drug, from CZP-treated pregnant women to their infants. Methods CRIB was a pharmacokinetic (PK) study of women ≥30 weeks pregnant receiving commercial CZP for a locally approved indication (last dose ≤35 days prior to delivery). Blood samples were collected from mothers, umbilical cords and infants at delivery, and infants again at weeks 4 and 8 post-delivery. CZP plasma concentrations were measured with a highly sensitive and CZP-specific electrochemiluminescence immunoassay (lower limit of quantification 0.032 μg/ mL). Results Sixteen women entered and completed the study. Maternal CZP plasma levels at delivery were within the expected therapeutic range (median [range] 24.4 [5.0–49.4] μg/mL). Of the 16 infants, 2 were excluded from the per-protocol set: 1 due to missing data at birth and 1 due to implausible PK data. Of the remaining 14 infants, 13 had no quantifiable CZP levels at birth (<0.032 μg/mL), and 1 had a minimal CZP level of 0.042 μg/mL (infant/mother plasma ratio 0.0009); no infants had quantifiable CZP levels at weeks 4 and 8. Of 16 umbilical cord samples, 1 was excluded due to missing data; 3/15 had quantifiable CZP levels (maximum 0.048 μg/mL). Conclusions There was no to minimal placental transfer of CZP from mothers to infants, suggesting lack of in utero foetal exposure during the third trimester. These results support continuation of CZP treatment during pregnancy, when considered necessary. Trial registration number NCT02019602; Results.

Objective: A number of open‐label studies have suggested the potential benefit of rituximab (RTX) in systemic lupus erythematosus (SLE). However, in 2 recent randomized controlled trials (RCTs) of RTX, the primary end points were not met. We undertook this study to evaluate the safety and efficacy of RTX in off‐trial patients with SLE seen in regular clinical practice.Methods: We analyzed prospective data from the French AutoImmunity and Rituximab (AIR) registry, which includes data on patients with autoimmune disorders treated with RTX.Results: One hundred thirty‐six patients received treatment for SLE. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) was 11.3 ± 8.9 at baseline. Severe infections were noted in 12 patients (9%), corresponding to a rate of 6.6/100 patient‐years. Most severe infections occurred within the first 3 months after the last RTX infusion. Five patients died, due to severe infection (n = 3) or refractory autoimmune disease (n = 2). Overall response was observed in 80 of 113 patients (71%) by the SELENA–SLEDAI assessment. Efficacy did not differ significantly between patients receiving RTX monotherapy and those receiving concomitant immunosuppressive agents (who had higher baseline disease activity). Articular, cutaneous, renal, and hematologic improvements were noted in 72%, 70%, 74%, and 88% of patients, respectively. Among responders, 41% experienced a relapse of disease, with a response in 91% after retreatment with RTX.Conclusion: Data from the AIR registry show a satisfactory tolerance profile and clinical efficacy of RTX in patients with SLE. The contrasting results with those from recent RCTs leave open the question of the therapeutic use of RTX in SLE. Additional controlled studies with new designs are needed to define the place of RTX in the therapeutic arsenal for SLE.

Objectives This project was undertaken to assess the risk of malignancy in patients with rheumatoid arthritis treated with tumour necrosis factor inhibitors (TNFi) in clinical practice, as recorded in prospective, observational studies. Methods The authors undertook comprehensive searches of MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and American College of Rheumatology, European League against Rheumatism and British Society for Rheumatology conference abstracts according to a prespecified protocol. Results The searches identified 2039 full-text papers and 1979 conference abstracts, of which 21 full texts and eight abstracts met the inclusion criteria. The pooled estimate for the risk of all-site malignancy from seven studies was 0.95 (95% CI 0.85 to 1.05). Two studies reported there was no evidence that longer exposure to TNFi agents increased the risk of malignancy. In patients with previous malignancies there was a higher risk of a new/recurring malignancy. This risk was not increased further by exposure to TNFi, although CI were wide. Results from four studies showed that patients treated with TNFi have a significantly increased risk of developing a non-melanoma skin cancer (1.45, 95% CI 1.15 to 1.76). In addition, patients are at an increased risk of developing melanoma, as the pooled estimate from two studies was 1.79 (95% CI 0.92 to 2.67). The pooled estimate for the risk of lymphoma was 1.11 (95% CI 0.70 to 1.51). Conclusions This systematic review and meta-analysis shows that TNFi treatments do not increase the risk of malignancy, particularly lymphoma. However, they do appear to increase the risk of skin cancer, including melanoma.

Primary Sjögren syndrome is a systemic autoimmune disease characterized by dryness, pain, and fatigue. Systemic manifestations occur in approximately one-third of patients.¹ Evidence-based therapy for primary Sjögren syndrome is largely limited to symptomatic treatments of dryness.² No conclusions can be drawn regarding the efficacy of biologic treatments currently evaluated, such as rituximab (because of controversial results),^3-5 abatacept (open study published in abstract form), or belimumab (open study).⁶ However, the potential safety concerns of these treatments must be taken into account in a disease for which life-threatening complications are infrequent.

Objective: The risk of severe infection is a crucial factor in the assessment of the short‐term risk:benefit ratio of biologic drugs in rheumatoid arthritis (RA). There is no increase in severe infections in RA patients treated with rituximab (RTX) in controlled trials, but this has not yet been assessed in daily practice. We undertook this study to investigate the occurrence of and risk factors for severe infections in off‐trial patients using data from the AutoImmunity and Rituximab (AIR) registry.Methods: The AIR registry was set up by the French Society of Rheumatology. The charts of patients with severe infections were reviewed.Results: Of the enrolled patients, 1,303 had at least 1 followup visit at 3 months or later, with a mean ± SD followup period of 1.2 ± 0.8 years (1,629 patient‐years). Eighty‐two severe infections occurred in 78 patients (5.0 severe infections per 100 patient‐years), half of them in the 3 months following the last RTX infusion. Multivariate analysis showed that chronic lung disease and/or cardiac insufficiency (odds ratio 3.0 [95% confidence interval 1.3–7.3], P = 0.01), extraarticular involvement (odds ratio 2.9 [95% confidence interval 1.3–6.7], P = 0.009), and low IgG level (<6 gm/liter) before initiation of RTX treatment (odds ratio 4.9 [95% confidence interval 1.6–15.2], P = 0.005) were significantly associated with increased risk of a severe infection.Conclusion: The rate of severe infections in current practice is similar to that reported in clinical trials. The risk factors for severe infections include chronic lung and/or cardiac disease, extraarticular involvement, and low IgG before RTX treatment. This suggests that serum IgG should be checked and the risk:benefit ratio of RTX discussed for patients found to have low levels of IgG.