With the introduction of biologic disease-modifying anti-rheumatic drugs (DMARDs) the armamentarium to fight rheumatoid arthritis (RA) has been dramatically enlarged.
A combination of lymphocyte counts and plasmablast frequency identifies patients with rheumatoid arthritis who will not benefit from rituximab with high probability.
With the introduction of biologic disease-modifying anti-rheumatic drugs (DMARDs) the armamentarium to fight rheumatoid arthritis (RA) has been dramatically enlarged. However, we are unable to predict which of these therapies would be optimal for a certain patient. For example, B cell depletion with the chimeric monoclonal antibody rituximab (RTX) is an effective treatment strategy for RA. However, a considerable proportion of around 30 % of patients with RA treated with RTX fail to respond, particularly after previous therapy with tumor necrosis factor (TNF)-α inhibitors. Identification of patients likely to respond to RTX treatment would result in an optimized treatment strategy reducing unnecessary socio-economic costs and potential side effects. Currently available clinical and laboratory parameters predicting the success of RTX therapy include the presence of rheumatoid factor (RF) and/or anti-citrullinated peptide antibodies (ACPA), and the absence of current glucocorticoid therapy. In addition, high serum calprotectin has been associated with good or moderate response to RTX. Furthermore, several authors have demonstrated that patients with RA who have a high frequency of plasmablasts are less likely to respond to RTX. All these factors, however, have been established to predict EULAR response. Current recommendations for the treatment of RA define remission or low disease activity (LDA) in patients with long-standing disease as the goal of treatment after 6 months, a target that is not achieved with a moderate EULAR response in many cases.
Rationale behind research:
Whether factors other than B cell subsets or their products might help us to find the optimal therapy for a particular patient is still unknown. Thus, the influence of RTX on T cells became an alternative focus of recent investigations.
Objective:
Study outcomes:
Complete blood count, lymphocyte analysis, and assessment of disease activity score in 28 joints (DAS28) using the erythrocyte sedimentation rate (ESR) were carried out before RTX treatment and at week 24.
Lymphocyte analysis blood cell counts in peripheral blood samples were obtained using a Beckman Coulter HMX hematology analyzer. For lymphocyte subsets determination, whole blood was stained for CD45, CD3, CD19, CD4, CD8, CD56, and CD16 using the BD Multitest IMK kit. After fixation and erythrocyte lysis according to the manufacturer’s protocol, cells were analyzed on a FACS Calibur flow cytometer (Becton Dickinson) using FACS Diva software (Becton Dickinson).
Time Points: Baseline and at week 24
Outcomes:
This is the first nationwide population-based study known till now which has explored the relationship between osteoporosis and subsequent migraine in an Asian population. During the follow-up period, migraine developed in 2.73 % (1110) patients with osteoporosis and in 1.85 % (750) patients without osteoporosis. Patients with osteoporosis, particularly those with high CCI score, female gender, hypertension, depression, asthma, allergic rhinitis, obesity, and tobacco use disorder, had a high migraine risk. The exact mechanisms underlying the relationship between migraine and osteoporosis are likely to be elusive. However, several lines of evidence in the literature suggest that osteoporosis and migraine have a shared pathophysiology. Gallai et al. showed that individuals suffering from migraine headaches had lower plasma and saliva magnesium levels between the attacks compared to controls without migraine headaches. Both osteoporosis and migraine are associated with hypomagnesemia, which suggests an interplay between osteoporosis and migraine. Secondly, the relationship between migraine and osteoporosis might be explained at least partly by their common inflammatory mediators. Inflammatory cytokines associated with osteoporosis such as tumor necrosis factor-αand IL-6 are elevated at the onset of migraine attacks. Finally, C-reactive protein, which increases during systemic inflammation, is elevated in both osteoporosis and migraine. Thus, the inflammatory state caused by osteoporosis may increase the frequency or severity of migraine headaches by exacerbating the inflammatory response.
Clinicians should be aware that osteoporosis is a potential risk factor for migraine. Further studies are recommended to confirm this association and to explore its mechanisms.
This study described the combination of biomarkers, i.e.,
high LC and plasmablast frequency at baseline, that reliably identify patients
who are likely to fail to respond to RTX treatment.
Arthritis Research & Therapy 2016; 18:190
A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study
Martin H. Stradner et al.
Comments (0)