The effect of TNF-α inhibitors (TNFi), with or without concomitant NSAIDs, on radiographic progression in axial SpA remains unclear. Therefore, we performed a systematic literature review up to January 2019 to determine whether longer use of standard dose TNFi is superior vs lower duration or lower dose TNFi therapy, conventional synthetic DMARDs alone, or no therapy in inhibiting radiographic progression in patients with axial SpA. Our search yielded 373 titles of which 14 full text articles and five abstracts were eligible for quantitative analysis. Studies had an overall moderate to critical risk of bias. Data could not be pooled due to clinical and methodological heterogeneity. Individual studies showed conflicting results with mainly no significant difference in radiographic progression when comparing effect of TNFi therapy to no TNFi therapy or when comparing to less TNFi therapy until 2 years of follow-up. Results that are more significant are shown after 2 years’ follow-up, mainly in subgroups with baseline syndesmophytes. Data on the additional or synergistic effect of concomitant NSAID use were inconclusive.

PASS cutoff values for physical function are robust across different PROM in patients with knee OA. Our results indicate that PASS values are not consistent across dimensions and rheumatic diseases, and that the use of a generic PASS value for patients with OA or even patients with other rheumatic diseases might not be justifiable.

BackgroundA standard low-dosing schedule of rituximab (RTX; 2 × 500 mg or 1 × 1000 mg) is as effective for active rheumatoid arthritis (RA) as the registered dose (2 × 1000 mg). Moreover, several small uncontrolled studies suggest that even lower-dosed treatment with RTX also leads to good treatment response in patients with RA. Retreatment with such an ‘ultra-low’ dose RTX in patients who responded well to RTX induction treatment is of special interest, as long-term use of lower RTX doses may lead to shorter infusion duration, lower risk of adverse events and lower costs. However, the effect of ultra-low dose of RTX has not been investigated using a controlled trial of proper design and dimensions.Methods/DesignREDO is an investigator driven six-month pragmatic, double-blind, randomised controlled non-inferiority trial on the effects of ultra-low-dose RTX (1 × 500 or 1 × 200 mg) compared to standard low dose (1 × 1000 mg) in RA patients who are being retreated with RTX. A total of 140 RA patients, having reached low disease activity (DAS28CRP < 2.9) after the previous RTX infusion and DAS28CRP < 3.5 at moment of retreatment, are randomised in a ratio of 1:2:2 to 1 × 1000 mg, 1 × 500 mg or 1 × 200 mg. The primary objective is testing non-inferiority of the ultra-low-dose vs. standard low-dose RTX, by comparing mean change in DAS28CRP from baseline to six months to the non-inferiority margin of 0.6. Secondary outcomes over the same period are: function; quality of life; safety; costs; and pharmacokinetics and dynamics as process measures.DiscussionThis study protocol shares characteristics of both early dose finding trials as well as late pragmatic clinical studies. Several choices in the design of this trial are described and possible consequences for RA treatment and expected biosimilar introduction are discussed.Trial registrationDutch Trial Register, NTR6117. Registered on 15 November 2016 (CMO NL57520.091.16, 8 November 2016)Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2134-x) contains supplementary material, which is available to authorized users.

ObjectivePolymyalgia rheumatica (PMR) is an inflammatory rheumatic disease characterised by pain and stiffness of neck, shoulder-and hipgirdle, typically with elevated acute phase reactants (APR). However, patients may present with normal APR. Our aim was to explore whether normal APR were due to 1) 'caught early in the disease', 2) misdiagnosis, or 3) a distinct subset of PMR with different clinical presentation and prognosis. Methods This was a retrospective cohort study on patients with clinical PMR diagnosis visiting the rheumatologists of theSint Maartenskliniek from April 2008 to September 2017. ResultsOf 454 patients, 62 patients had normal, and 392 elevated APR. Normal APR patients had longer symptom duration before diagnosis (13 vs. 10 weeks; p=0.02), however, during follow-up 31% developed elevated APR. In elevated APR patients with previous APR data available while already symptomatic, 58% had earlier normal APR. Fewer normal APR patients had peripheral arthritis (2% vs. 9%;p=0.04), and anaemia (17% vs. 43%; p=0.001). More often they had a previous PMR diagnosis (16% vs. 8%; p=0.057) and a shorter median time to glucocorticoid-free remission (552 vs. 693 days; n=36 vs. 160; p=0.02). Route of GC administration differed between groups (p=0.026). Fewer patients received methotrexate; 3 vs. 12%; p=0.046). No difference in alternative diagnosis was observed. Conclusion PMR patients with long-term normal APR seem to be a milder subset of PMR in clinical presentation and prognosis.Additionally, our data also suggest there is a subgroup with normal APR who are caught early in the disease. Misdiagnosis does not appear to play a role.

Background: Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. Methods: We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. Discussion: More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences.