Treatment with Targeted Therapy in Patients with Psoriatic Arthritis and Inadequate Response to Methotrexate: Proposal for a Rational Strategy.

INTRODUCTION: The therapeutic arsenal for psoriatic arthritis (PsA) is gradually being expanded, but the use of these targeted treatments must be optimal. Our objective was to guide the choice of targeted therapy to use as first-line treatment in a patient with PsA in whom methotrexate (MTX) has failed. METHODS: We searched for literature data in PubMed with the appropriate keywords for the six points of our argument: (1) the tolerance of MTX; (2) the efficacy of targeted therapies combined with MTX vs monotherapy; (3) immunogenicity of anti-tumor necrosis alpha (TNFα) monoclonal antibodies (mAbs); (4) immunogenicity of anti-interleukin (IL)-17, anti-IL-12/23, and anti-IL-23 mAbs; (5) the therapeutic maintenance of anti-TNFα mAbs when combined or not with MTX; (6) the therapeutic maintenance of anti-IL-17 vs anti-TNFα mAbs as first-line targeted therapy. RESULTS: The proposed rational strategy is as follows: in case of initiation of an anti-TNFα agent, maintaining treatment with MTX seems preferable, even in the absence of evidence of the superior efficacy of the combination, to avoid immunization and reduced therapeutic maintenance; in case of initiation of anti-IL-17, anti-IL-12/23, anti-IL-23 agents, or Janus kinase (JAK) inhibitors, again in the absence of evidence of the superior efficacy of the combination, discontinuing MTX therapy may be possible, at least in two steps, after verifying the efficacy of the targeted therapy initiated on the joints and skin. CONCLUSION: We have data from the literature to guide the choice of targeted therapy to use as first-line treatment in a patient with PsA in whom MTX has failed.

Unmet needs in axial spondyloarthritis. Proceedings of the French spondyloarthritis taskforce workshop.

The progress observed over the last 30 years in the field of axial spondyloarthritis (axSpA) has not made it possible to answer all the current questions. This manuscript represents the proceedings of the meeting of the French spondyloArthitiS Task force (FAST) in Besançon on September 28 and 29, 2023. Different points of discussion were thus individualized as unmet needs: biomarkers for early diagnosis and disease activity, a common electronic file dedicated to SpA nationwide, a better comprehension of dysbiosis in the disease, a check-list for addressing to the rheumatologist, adapt patient reported outcomes thresholds for female gender, implementation of comorbidities screening programs, new imaging tools, in research cellular and multi omics approaches, grouping, at a nationwide level, different cohorts and registries, therapeutic strategy studies, consensual definition of difficult to treat disease and management, preclinical stage of the disease, mastering AI as a tool in the various aspects of research. These elements may represent a framework for the research agenda in axSpA for the years to come.

Recommendations of the French Society of Rheumatology for the management in current practice of patients with polymyalgia rheumatica.

OBJECTIVE: To develop recommendations for the routine management of patients with polymyalgia rheumatica (PMR). METHODS: Following standard procedures, a systematic review of the literature by five supervised junior rheumatologists, based on the questions selected by the steering committee (5 senior rheumatologists), was used as the basis for working meetings, followed by a one-day plenary meeting with the working group (15 members), leading to the development of the wording and determination of the strength of the recommendations and the level of agreement of the experts. RESULTS: Five general principles and 19 recommendations were drawn up. Three recommendations relate to diagnosis and the use of imaging, and five to the assessment of the disease, its activity and comorbidities. Non-pharmacological therapies are the subject of one recommendation. Three recommendations concern initial treatment based on general corticosteroid therapy, five concern the reduction of corticosteroid therapy and follow-up, and two concern corticosteroid dependence and steroid-sparing treatments (anti-IL-6). CONCLUSION: These recommendations take account of current data on PMR, with the aim of reducing exposure to corticosteroid therapy and its side effects in a fragile population. They are intended to be practical, to help practitioners in the day-to-day management of patients with PMR.

Effects of disease-modifying anti-rheumatic drugs on sacroiliac MRI score in axial spondyloarthritis: a systematic review and meta-analysis.

INTRODUCTION: Sacroiliac bone marrow edema is an important factor in the diagnosis and management of axial spondyloarthritis (axSpA). The aim of this meta-analysis is to assess the effect of the different bDMARDs and tsDMARDs on the SPARCC score at 12-16 and 48-52 weeks. METHODS: A systematic review, performed on PubMed (including Medline), Cochrane (CENTRAL) and DOAJ databases, included randomized controlled studies evaluating the sacroiliac joint (SIJ) SPARCC score at 12-16 or 48-52 weeks in patients with axSpA meeting the ASAS 2009 criteria or the modified New York criteria. We included studies evaluating the effects of the different treatments on the SPARCC score of SIJ in axial spondyloarthritis in comparison to a control group. RESULTS: Eighteen studies were included in the meta-analysis. Nine studies evaluated the effect of TNFα inhibitors (TNFi), three for IL-17 inhibitors, and four for JAK inhibitors. At 12 and 16 weeks, SIJ SPARCC score was significantly improved by TNFi (WMD: - 3.29 [95% CI - 4.25; - 2, 34]), by IL-17 inhibitors (WMD: - 4.66 [95% CI - 6.22; - 3.09]), and by JAK inhibitors (JAKi) (WMD: - 3.06 [95% CI - 3.24; - 2.89]). There was no difference between the molecule subgroups. At 48-52 weeks, TNFα inhibitors reduced more SIJ SPARCC, but not significantly (WMD: - 2.26 [95% CI - 4.94; 0.42]), than placebo groups who began a TNFi treatment with delay. CONCLUSION: Our meta-analysis shows a comparable improvement of the SIJ SPARCC score regarding TNFi, JAKi, and IL-17 inhibitors at three months and suggests the presence of an opportunity window. Key Points • Anti-TNF Ab, anti-IL17 Ab, and JAK inhibitor treatments reduce the sacroiliac joint SPARCC scores. • There is no difference between the different treatments in the reduction of the sacroiliac joint SPARCC score after 3 months in axial spondyloarthritis.

Improved Olfactory Deposition of Theophylline Using a Nanotech Soft Mist Nozzle Chip.

Currently, nasal administration of active pharmaceutical ingredients is most commonly performed using swirl-nozzle-based pump devices or pressurized syringes. However, they lead to limited deposition in the more active regions of the nasal cavity, especially the olfactory region, which is crucial for nose-to-brain drug delivery. This research proposes to improve deposition in the olfactory region by replacing the swirl nozzle with a nanoengineered nozzle chip containing micrometer-sized holes, which generates smaller droplets of 10-50 µm travelling at a lower plume velocity. Two nanotech nozzle chips with different hole sizes were tested at different inhalation flow rates to examine the deposition patterns of theophylline, a hyposmia treatment formulation, using a nasal cavity model. A user study was also conducted and showed that the patient instructions influenced the inhalation flow rate characteristics. Targeted flow rates of between 0 and 25 L/min were used for the in vitro deposition study, yielding 21.5-31.5% olfactory coverage. In contrast, the traditional swirl nozzle provided only 10.8% coverage at a similar flow rate. This work highlights the potential of the nanotech soft mist nozzle for improved intranasal drug delivery, particularly to the olfactory region.