Th17 cell responses in spondyloarthritis.

Targeting IL-17 has become an important option in the current treatment of spondyloarthritis (SpA). To place this therapeutic advancement in context, we review the discovery and properties of this cytokine, noting those which predispose to inflammation and led to it being considered as an attractive target for the treatment of arthritis, especially SpA. The processes that regulate the differentiation of IL-17-producing cells, particularly Th17 CD4+ T cells, have been investigated thoroughly, including the role of IL-23, as these point to additional potential therapies as alternatives to direct IL-17 blockade. IL-17 is a critical cytokine in combatting infection, particularly caused by fungi, but it also has an important role in maintaining epithelial barrier functions, especially in the gut. Both these functions help predict possible adverse effects of IL-17 blockade. Finally, we review the current evidence for the use of IL-17 blockade in various forms of SpA and briefly speculate on future developments.

Feasibility, reliability, and sensitivity to change of four radiographic scoring methods in patients with psoriatic arthritis.

OBJECTIVE: We set out to assess the feasibility, reliability, and sensitivity to change of 4 radiographic scoring methods in psoriatic arthritis (PsA). METHODS: Hand and feet radiographs from 50 patients with PsA were scored at 2 time points by 2 assessors with each of the following methods: modified Steinbrocker score, modified Sharp score (MSS), modified Sharp/van der Heijde score (SHS), and the Ratingen score for PsA. The radiographs of 10 patients were scored by both assessors to assess reliability using intraclass correlation coefficients (ICCs). Sensitivity to change was estimated using a standardized response mean (SRM) and smallest detectable change (SDC). RESULTS: The patients' mean ± SD age at baseline was 50 ± 12.1 years, the mean ± SD disease duration was 10 ± 8.4 years, and the mean ± SD followup period was 25 ± 9.6 months. Intrarater reliability was excellent for all methods (ICC >0.97). Interrater reliability was highest for the SHS (ICC 0.95-0.99). The percentage SDC for the Steinbrocker method, the Ratingen method, the MSS, and the SHS was 2.9%, 2.1%, 1.4%, and 1.2%, respectively, and the SRMs were 0.46, 0.44, 0.77, and 0.79, respectively. The mean time to score each of the Steinbrocker method, the Ratingen method, the MSS, and the SHS was 6.2, 10.5, 14.6, and 14.4 minutes, respectively. CONCLUSION: The SHS method was the most reliable and sensitive to change but took longer to perform. The Steinbrocker method is the most feasible but lacks the sensitivity of the SHS. The SDC of the Ratingen method is close to that of the SHS and MSS, but is quicker to perform.

Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas.

OBJECTIVE: Reports suggest that up to 70% of patients with microprolactinomas treated with dopamine agonist therapy may achieve long-term normoprolactinaemic remission following drug withdrawal. Yet, there is no consensus on the duration of therapy nor is therapeutic interruption universally practised. We have assessed remission rates in a large cohort of treatment-naive subjects with microprolactinomas. Subjects received dopamine agonist (DA) therapy with either cabergoline or bromocriptine for a period of 2 to 3 years in the majority of cases, followed by a trial of treatment withdrawal. DESIGN: Retrospective analysis of clinic records of 89 patients (mean age 32.7 +/- 8.4 years, 84 women and 5 men) who had received either cabergoline (n = 67) (0.5-3 mg weekly) or bromocriptine (n = 22) (2.5-10 mg daily) for a mean duration of 3.1 years. RESULTS: Following withdrawal of therapy, 57 subjects developed recurrence (64%) and the mean time to recurrence was 9.6 months (range 1-44 months), while 32 subjects (36%) remained in remission beyond 1 year (mean 3.6 years, range 1-7 years). There was no difference in remission rates between subjects treated with cabergoline (n = 21) and bromocriptine (n = 11), but a direct relationship between pretreatment prolactin concentration and risk of recurrent symptomatic hyperprolactinaemia was observed. No subjects developed clinical features to suggest tumour expansion following therapeutic discontinuation. CONCLUSIONS: This study confirms that abrupt withdrawal of chronic dopamine agonist therapy, following 2 to 3 years of treatment is safe and associated with long-term remission in 30-40% of subjects with microprolactinomas. This therapeutic strategy is convenient and applicable in clinical practice.