An increased risk of non-melanoma skin cancer during TNF-inhibitor treatment in psoriasis patients compared to rheumatoid arthritis patients probably relates to disease-related factors.

BACKGROUND: Concerns exist about a risk of non-melanoma skin cancer (NMSC) in psoriasis patients and rheumatoid arthritis (RA) patients treated with TNF-inhibitors. However, current data also show that in some psoriasis patients, NMSC is diagnosed relatively short after the start of TNF-inhibitors, which suggests that these NMSC can be explained by previous therapies instead of by TNF-inhibitor therapy. OBJECTIVE: To investigate whether there was a difference in time until first NMSC and the rate of NMSC between psoriasis and RA patients on TNF-inhibitors. METHODS: Time until first NMSC and the rate of NMSC were compared between psoriasis and RA patients from the same region treated with TNF-inhibitors and followed up for at least one year in prospective cohort studies, by using Cox regression and Poisson regression. Both analyses were corrected for confounders (age, gender, disease duration, prior NMSC, duration of anti-TNF and other systemic therapies). RESULTS: The NMSC risk was significantly higher in the psoriasis group [fully adjusted HR 6.0 (1.6-22.4 95%CI)] with a shorter time until first NMSC in psoriasis compared to RA. By Poisson regression, psoriasis patients had a 5.5 (2.2-13.4 95%CI) higher rate of NMSC. CONCLUSION: The time until first NMSC was significantly shorter and the rate of NMSC was significantly higher in psoriasis compared with RA. This indicates that disease-related factors like phototherapy may be important contributing factors to NMSC diagnosed in psoriasis patients treated with TNF-inhibitors.

Prevalence and predictors of health care use in patients with early hip or knee osteoarthritis: two-year follow-up data from the CHECK cohort.

OBJECTIVE: To describe health care utilization (HCU) and predict analgesic use and health professional (HP) contact at baseline and 2 years in individuals with early symptomatic hip and/or knee osteoarthritis (OA). DESIGN: Baseline and two-year data on HCU of the 1002 participants from the multi-centre Cohort Hip & Cohort Knee study were used. Six forms of health care services were described: analgesic use, supplement use, contact with a General Practitioner (GP), contact with a HP, contact in secondary care, and alternative medicine use. Multivariable logistic regression was performed in order to identify predisposing, enabling and disease-related variables that predict analgesic use and HP contact at 2 years; treatment modalities of first choice in early OA. RESULTS: For the hip (n=170), the knee (n=414) and the hip and knee (n=418) group analgesic use (38%, 29% and 47%, respectively), contact with a GP (32%, 38% and 36%, respectively) and contact with a HP (26%, 18% and 20%, respectively), were reported most often at baseline. Contact with a GP significantly decreased, supplement use increased (to about one third), and other treatment modalities remained stable at 2 years. In all three groups, analgesic use at baseline was the strongest predictor for analgesic use at 2 years, whereas contact with a HP at baseline was the strongest predictor of contact with a HP after 2 years. Belonging to a first generation minority was a predisposing risk factor [Odds Ratio (95%-CI), 8.72 (1.55-48.97)] for analgesic use in the hip and knee group. CONCLUSIONS: In early OA, familiarity with HCU and other predisposing factors are, apart from disease-related factors strongly associated with HCU at 2 years. Further research is necessary to examine whether our findings reflect sub-optimal management of early OA in terms of efficacy and equity.

Abatacept modulates proinflammatory macrophage responses upon cytokine-activated T cell and Toll-like receptor ligand stimulation.

OBJECTIVES: We investigated whether Abatacept might reduce proinflammatory cytokine production by macrophages upon contact with cytokine activated T cells and/or stimulation with TLR ligands. METHODS: Macrophages and cytokine stimulated T cells (Tck) were added together in the presence of Abatacept or a control Ig, with or without TLR ligands. The production of cytokines was determined by luminex. RESULTS: Abatacept reduced Tck-induced production of TNFa by macrophages. Tck and TLR ligands synergistically induced the production of proinflammatory cytokines by macrophages, especially IL-12p70. The production of IL-12p70 coincided with the production of IFNg, which were both reduced in the presence of Abatacept. CONCLUSIONS: Tck induce the production of TNFa by macrophages and facilitate the highly increased production of proinflammatory cytokines in the presence of TLR ligands. Abatacept was shown to potently suppress these pathways suggesting that its role may extend beyond antigen specific T cell mediated effector function.

Evidence-based tailored conservative treatment of knee and hip osteoarthritis: between knowing and doing.

OBJECTIVE: Insufficient data are available on the efficacy of combined conservative interventions recommended by treatment guidelines for knee/hip osteoarthritis (OA). The aims of this observational cohort study were (i) to estimate the results of an evidence-based 12-week tailored multimodal conservative treatment protocol for patients with knee/hip OA and (ii) to identify predictors for response. METHODS: After obtaining data on previous OA-related interventions, multimodal treatment was offered to patients with knee and/or hip OA at a specialized outpatient clinic. Treatment with analgesics was tailored using a numeric rating scale (NRS) for pain, aiming for NRS ≤ 4. The following outcome measures were assessed: (i) the proportion of patients fulfilling OMERACT-OARSI (Outcome Measures in Rheumatoid Arthritis Clinical Trials/Osteoarthritis Research Society International) responder criteria and (ii) the proportion of patients with NRS pain ≤ 4 after 12 weeks. RESULTS: A total of 183 out of 299 patients was included. OMERACT-OARSI responder criteria were fulfilled at 12 weeks in 47% of patients; 39% reached NRS pain ≤ 4. The only independent predictor for response was the number of previously used non-steroidal anti-inflammatory drugs (NSAIDs). The majority of patients had not been exposed adequately to conservative treatment modalities for knee and/or hip OA in the past (81%). CONCLUSION: Evidence-based multimodal conservative treatment using a standardized protocol for knee and/or hip OA is feasible and successful in 47% of patients. In general, response could not be predicted. Basic first-line recommended conservative treatment options have not been used adequately prior to referral to secondary care in the vast majority of patients.

Influence of guideline adherence on outcome in a randomised controlled trial on the efficacy of methotrexate with folate supplementation in rheumatoid arthritis.

OBJECTIVE: To study the influence of rheumatologists' adherence to a methotrexate guideline on efficacy and toxicity in the treatment of rheumatoid arthritis. METHODS: In a 48 week randomised controlled trial of methotrexate, comparing folates with placebo, rheumatologists were advised on methotrexate dosage using a guideline reflecting daily practice. The influence of guideline non-adherence on outcome was analysed using generalised estimating equations and survival analysis. RESULTS: In 51% of the 411 study patients the guidelines were always followed. Non-adherence resulted in lower doses of methotrexate in 25% of cases, and higher doses in 24%. The reduction in the disease activity score was significantly greater (mean -0.4; p = 0.0085) in the adherent group than in the "low dose" group; the "high dose" group did not differ from the adherent group. Dropout caused by severe adverse events did not differ between the three groups. CONCLUSIONS: There is an indication that adherence to guidelines on methotrexate dosage may benefit patients with rheumatoid arthritis by improving disease activity without increasing toxicity. For definite proof, a randomised controlled trial comparing guideline supported dosing with usual care is needed.