NCT00209859.

Objective. To investigate whether disease control can be achieved in early active rheumatoid arthritis (RA) by treatment with methotrexate and intraarticular betamethasone, and whether the addition of cyclosporine to the regimen has any additional effect.Methods. Patients (n ‫؍‬ 160) were randomized to receive methotrexate 7.5 mg/week plus cyclosporine 2.5 mg/kg of body weight/day (combination therapy) or methotrexate plus placebo-cyclosporine (monotherapy). At weeks 0, 2, 4, 6, and 8 and every 4 weeks thereafter, betamethasone was injected into swollen joints (maximum 4 joints or 4 ml per visit). Beginning at week 8, if synovitis was present, the methotrexate dosage was increased stepwise up to 20 mg/week, with a subsequent stepwise increase in the cyclosporine or placebo-cyclosporine dosage up to 4 mg/kg. Results. At 52 weeks, 20% improvement according to the American College of Rheumatology criteria (ACR20) was achieved in 85% of the combination therapy group versus 68% of the monotherapy group (P ‫؍‬ 0.02). The median individual overall ACR response (ACR-N) in the 2 groups was 80.0% (interquartile range 40.1-91.8%) and 54.5% (interquartile range 2.4-87.8%), respectively (P ‫؍‬ 0.025). At 48 and 52 weeks, ACR remission criteria were met in 35% of the combination therapy group and 28% of the monotherapy group. Progression in the Larsen score at 52 weeks was -0.2 ؎ 6.5 and 0.4 ؎ 6.9 (mean ؎ SD) in the combination therapy and monotherapy groups, respectively. Serum creatinine levels increased by 7%, and hypertrichosis was more prevalent, in the combination therapy group. Conclusion. Combined treatment with methotrexate and intraarticular glucocorticoid showed excellentSupported by a grant from the Danish Rheumatism Association. Novartis Healthcare Denmark A/S kindly provided cyclosporine and placebo-cyclosporine and sponsored an independent good clinical practice monitor. Nycomed provided methotrexate, folic acid, and calcium/vitamin D. Schering-Plough provided injectable betamethasone. Merck, Sharp, & Dohme provided alendronate.

A geneml and detailed analysis is given of the phenomenon of chemically-induced dynamic electron polarization (CIDEP) by means of the stochastic-Liouville method in accordance with the earlier preliminary report. The finite-difference technique employed permits rapid and convergent solutions without requiring any untoward assumptions on the nature of the models. The dependence of the polarization on the exchange interaction J (r), the Larmor frequency differences between the interacting pair of radicals, diffusion mtes, and rates of spin-selective chemical reactions are given in detail. It is shown that models in which J(r) is taken to decay exponentially with r, the radical-separation distance of the radical pair, yield results which are distinctly different from those for a contact exchange model, when J o [the value of J(r) when r is at the distance of closest approach] is appreciable. The former, more realistic model yields substantial polarizations asymptotically independent of J o , but larger the slower the decrease of J(r) with rj the contact exchange model, however, rapidly goes to zero with increasing J o• These asymptotic values of polarization are predicted to be as high as 10-40 times the equilibrium polarizations (P. Q ) for sensible values of the relevant parameters, while for values of J o yielding maximum polarizations (generated at the formative reaction), they can be greater than 100 P eq. These results are of the correct order for agreement with recent experiments. The polarizations have been related to the CIDEP intensities that one may observe for typical schemes of radical production, reaction, and relaxation in order to allow a comparison of the theoretical predictions with experiment.

The earlier theoretical analysis for chemically induced dynamic electron polarization (CIDEP), based on the stochastic-Liouville equation, is generalized to explicitly include the spin-dependent exchange forces in the diffusive trajectories, thus permitting a consistent analysis of the simultaneous effects of exchange on both the spin-selective chemical reaction and CIDEP effects. The semiclassical treatment of diffusion under a ``classical'' force field due to the valence interactions requires the introduction of spin-dependent diffusive and reactive trajectories, and this is discussed for the Brownian-motion model utilized. Our results show that the polarization generated per fractional probability that singlets react (P ∞/F), is not sensitive to the actual details of the spin-selective reactive process (although the absolute polarization P∞ is sensitive to the reactive process), due presumably to the spatial distinction between interradical separations (r) for which the reaction may occur vs those for which CIDEP polarizations are developed. The former require ℏ|J(r)|/kT > 1 while for the latter ℏ|J(r)|/kT < 1, where J(r) is the exchange interaction. It is found that differences in the (nonreactive) diffusive trajectories for singlets and triplets give polarizations that are generally negligible compared to those which develop as a result of the spin-selective reaction (for our overdamped diffusive model). However, our results for more long-range Coulomb interactions between charged radicals show they can produce significant changes on P ∞/F that are quite sensitive to the magnitude of J. Thus ionic-concentration effects on P∞/F should be an important indicator of the CIDEP mechanism. Results are also given for the spin-depolarization process, whereby the effects of spin exchange on a radical pair, which initially collide with residual nonthermal polarization, are to destroy this polarization. The effective range of the spin exchange is found to be weakly enhanced as the range of J(r) is increased. Also, it is shown that, for several variations of a simple exponential dependence of J(r) on r, P∞ / F is hardly affected, although nonexponential dependences can introduce marked changes.

AimsIn Danish patients with inflammatory rheumatic diseases to explore self-protection strategies and health behaviour including adherence to disease-modifying antirheumatic treatment (DMARD) during the initial phase of the COVID-19 pandemic and again after the reopening of the society started. Furthermore, to identify characteristics of patients with high levels of anxiety and self-isolation.MethodsPatients in routine care followed prospectively in the nationwide DANBIO registry were invited to answer an online questionnaire regarding disease activity and COVID-19 infection, behaviour in March and June 2020. Responses were linked to patient data in DANBIO. Characteristics potentially associated with anxiety, self-isolation and medication adherence (gender/age/diagnosis/education/work status/comorbidity/DMARD/smoking/EQ-5D/disease activity) were explored with multivariable logistic regression analyses.ResultsWe included 12 789 patients (8168 rheumatoid arthritis/2068 psoriatic arthritis/1758 axial spondyloarthritis/795 other) of whom 65% were women and 36% treated with biological DMARD. Self-reported COVID-19 prevalence was 0.3%. Patients reported that they were worried to get COVID-19 infection (March/June: 70%/45%) and self-isolated more than others of the same age (48%/38%). The fraction of patients who changed medication due to fear of COVID-19 were 4.1%/0.6%. Female gender, comorbidities, not working, lower education, biological treatment and poor European Quality of life, 5 dimensions were associated with both anxiety and self-isolation.ConclusionIn >12 000 patients with inflammatory arthritis, we found widespread anxiety and self-isolation, but high medication adherence, in the initial phase of the COVID-19 pandemic. This persisted during the gradual opening of society during the following months. Attention to patients’ anxiety and self-isolation is important during this and potential future epidemics.