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Objective The aim of this study was to compare the efficacy and safety of rituximab (RTX) as a function of patient age. Methods We included all rheumatoid arthritis patients in the AutoImmunity and Rituximab registry with a 2-year followup. Results Of the 1,709 patients, 191 were age ≥75 years, 417 were ages 65–74 years, 907 were ages 50–64 years, and 194 were age 75 years). The reasons for discontinuation (inefficacy, adverse events) were the same in all 4 groups. Infections were more common in the elderly. Patients ages 65–75 years were more likely to be good responders than nonresponders at 1 year of followup than patients age ≥75 years (odds ratio 3.81, 95% confidence interval 1.14–12.79) after adjustment on disease duration, RF/anti-CCP positivity, corticosteroids, anti-TNF use, and baseline Disease Activity Score in 28 joints (DAS28). After the sixth month, the decrease in DAS28 score was less marked in the population age >75 years than in the group age

Resume Objectifs Le risque de lymphome est accru dans la polyarthrite rhumatoide (PR), contrairement a la spondylarthrite ankylosante (SA). Le role de l’EBV dans la survenue des lymphomes au cours de la PR reste discute. Methode Nous avons etudie de maniere prospective l’evolution de la charge virale EBV (CvEBV) de patients atteints de PR ou de SA traites par anti-TNFα, ainsi que le lien avec l’activite de la maladie. Resultats Les 46 patients atteints de PR (femmes : 82,6 %), etaient âgees de 52,7 ± 11,3 ans. La CvEBV a ete controlee a 9,72 ± 5,7 mois. Elle est devenue positive chez cinq patients et a augmente chez un autre (quatre sous etanercept, un sous adalimumab, un sous infliximab). Elle est devenue negative chez six patients (cinq patients sous adalimumab, un sous etanercept). Le DAS 28 est passe de 4,78 ± 1,1 a l’inclusion a 2,94 ± 1,24. Les 27 patients atteints de SA (hommes : 81,5 %) etaient âges de 45,1 ± 12,7 ans. La CvEBV a ete controlee a 12,9 ± 10,6 mois. Elle est devenue positive chez deux patients (7,4 %) (un sous infliximab, un sous adalimumab), indetectable chez un patient sous adalimumab. Sous traitement, le BASDAI est passe de 55,1 ± 16,2 a 17,8 ± 18,6. Une CvEBV positive est plus frequente dans la PR que dans la SA (p = 0,039). Aucun cas de lymphome n’a ete recense. Conclusion L’introduction d’un traitement anti-TNFα n’influence pas la CvEBV de patients traites pour une PR ou une SA.

Objective The risk of non-Hodgkin lymphoma is increased in rheumatoid arthritis (RA) but not in ankylosing spondylitis (AS). In RA, the degree of inflammation is closely associated with the lymphoma risk. Whether immunosuppressants such as methotrexate and TNFα antagonists affect the lymphoma risk in RA is unclear. The Epstein-Barr virus (EBV) may contribute to the pathogenesis of RA and may be involved in the development of lymphoma in patients taking methotrexate and/or TNFα antagonists, although these points remain debated. EBV load monitoring during immunosuppressive treatment may predict the occurrence of EBV-related lymphoma. Here, our objective was to prospectively measure the EBV load in patients receiving TNFα antagonists for RA or AS. Methods We prospectively studied patients with RA or AS before and after TNFα antagonist therapy initiation. The EBV load was measured in blood samples using the EBV R-gene Quantification Kit. Disease activity at the time of blood sampling was evaluated by determining the Disease Activity Score 28 (DAS28) in RA patients and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS patients. Results We included 46 patients with RA (82.6% women; mean age, 52.7 ± 11.3 years) and 27 with AS (men, 81.5%; mean age, 45.1 ± 12.7 years). In the RA group, the EBV load was measured at baseline and 9.72 ± 5.7 months later. The baseline EBV load was undetectable in 33 (70.2%) patients; mean EBV load in the 13 remaining patients was 9389copies/ml (3.47 log 10 ± 0.45). Baseline EBV load did not correlate with disease activity (DAS28). At the follow-up assay, the EBV load became positive in five patients and increased significantly in one patient (four patients on etanercept, one on adalimumab, and one on infliximab); it became negative in six patients (five on adalimumab and one on etanercept) and showed non-significant changes in six patients. Mean EBV load in patients positive at follow-up was 3.63 ± 0.52 log 10 copies/ml. Mean DAS28 was 4.78 ± 1.1 at baseline and 2.94 ± 1.24 at follow-up. At follow-up, a good EULAR response was noted in 33 (71.7%) patients and a moderate EULAR response in seven (15.2%) patients. In the AS group, the baseline EBV load measurement occurred after 12.9 ± 10.6 months. Baseline EBV load was undetectable in 25 (92.6%) patients; mean load in the remaining two patients was 4.15 ± 0.46 log 10 copies/ml. At follow-up, the EBV load became positive in two patients (one on adalimumab and one on infliximab) and became negative in one patient (on adalimumab). Mean load in positive patients was 3.33 ± 0.24 log 10 copies/ml. Mean BASDAI was 55.1 ± 16.2 at baseline and 17.88 ± 18.62 at follow-up. A positive EBV load was significantly more common in the RA group than in the AS group ( P = 0.039). EBV load changes did not differ significantly between the RA and AS groups or across TNFα antagonists. No cases of lymphoma were recorded. Conclusion Introducing TNFα antagonist therapy does not affect the EBV load in patients with RA or AS. EBV load monitoring is probably unnecessary in patients given TNFα antagonists for RA or AS.

Resume Les objectifs therapeutiques dans la polyarthrite rhumatoide (PR) du sujet âge ne sont pas differents de ceux de la PR du sujet plus jeune : controler les manifestations cliniques, prevenir les degâts structuraux, eviter le handicap fonctionnel, reduire la surmortalite. Le traitement est rendu plus difficile par la presence de pathologies associees et par l’augmentation des effets secondaires medicamenteux. Les anti-inflammatoires non steroidiens (AINS) exposent au triple risque cardiovasculaire, digestif et renal. La place de la corticotherapie reste controversee. Ses effets symptomatiques a court terme sur l’activite clinique et probablement a moyen terme sur l’aggravation structurale sont contrebalances par ses effets secondaires. L’efficacite du MTX a ete confirmee par l’analyse des essais cliniques et par les etudes observationnelles ; les patients âges n’ont pas plus d’effet secondaire que les sujets jeunes si leur fonction renale est normale. Les donnees sur les anti-TNF au cours des essais therapeutiques montrent une diminution de l’activite de la PR, une amelioration fonctionnelle. Les effets indesirables sont plus frequents chez le sujet âge mais cela s’observe egalement avec les traitements de fond ayant servi de comparateurs. L’etude des registres des anti-TNF confirme leur efficacite dans la prise en charge de la PR. Une augmentation du risque infectieux n’est pas retrouvee dans tous les registres. Pour diminuer le risque cardiovasculaire qui est multiplie par deux, un controle strict de l’activite de la maladie est necessaire ainsi qu’une prise en charge de tous les facteurs de risque cardiovasculaires.

The aim of this study was to compare the efficacy and safety of rituximab (RTX) as a function of patient age.We included all rheumatoid arthritis patients in the AutoImmunity and Rituximab registry with a 2-year followup.Of the 1,709 patients, 191 were age ≥75 years, 417 were ages 65–74 years, 907 were ages 50–64 years, and 194 were age50 years. At baseline, the elderly and very elderly patients presented with longer disease duration, a higher incidence of erythrocyte sedimentation rate and C-reactive protein level, a lower incidence of previous tumor necrosis factor α (TNFα) therapy, and a smaller number of previously used TNFα agents. Disease activity, rheumatoid factor (RF), or anti–cyclic citrullinated peptide (anti-CCP) antibodies and corticosteroid therapy were not statistically different among the groups. At 24 months, no significant difference was shown among the groups for RTX discontinuation rates (36.1% if age50 years, 32.6% if ages 50–64 years, 34.5% if ages 65–74 years, and 32.5% if age75 years). The reasons for discontinuation (inefficacy, adverse events) were the same in all 4 groups. Infections were more common in the elderly. Patients ages 65–75 years were more likely to be good responders than nonresponders at 1 year of followup than patients age ≥75 years (odds ratio 3.81, 95% confidence interval 1.14–12.79) after adjustment on disease duration, RF/anti-CCP positivity, corticosteroids, anti-TNF use, and baseline Disease Activity Score in 28 joints (DAS28). After the sixth month, the decrease in DAS28 score was less marked in the population age75 years than in the group age50 years.The efficacy and safety of RTX is affected by age.

The treatment of elderly-onset rheumatoid arthritis pursues the same objectives as in younger patients: to control the clinical manifestations, to prevent structural damage, to preserve function, and to decrease excess mortality. In the elderly, the presence of co-morbidities and increased rate of drug-related adverse effects raise specific therapeutic challenges. Nonsteroidal anti-inflammatory drugs are associated with cardiovascular, gastrointestinal, and renal adverse events. The role for corticosteroid therapy remains controversial. Although glucocorticoids provide a short-term decrease in clinical activity and probably a medium-term decrease in structural damage, these benefits are offset by numerous adverse effects. Methotrexate was effective in clinical trials and observational studies and did not produce a higher adverse event rate compared to younger patients, provided renal function was normal. Data on the efficacy of TNFalpha antagonists in therapeutic trials are available only for etanercept. Disease activity decreased and function improved. The adverse event rate was higher in older patients, but this was also true of the conventional drugs used as comparators. Registry data confirm that TNFalpha antagonist therapy is effective in RA. An increased rate of infections was found only in some registries. To combat the 2-fold cardiovascular risk increase associated with RA, disease activity should be stringently controlled and all cardiovascular risk factors managed aggressively.