Hydroxychloroquine in patients with inflammatory and erosive osteoarthritis of the hands: results of the OA-TREAT study-a randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial.

OBJECTIVES: Hand osteoarthritis (OA) is a condition characterised by cartilage degradation and frequently erosive changes. Analgesics and non-steroidal anti-inflammatory drugs are used for symptomatic relief but are often poorly tolerated or contraindicated. Previous publications suggest hydroxychloroquine (HCQ) as a possible treatment for hand OA. The OA-TREAT study aimed to investigate the efficacy and safety of HCQ in patients with inflammatory and erosive hand OA (EOA). METHODS: OA-TREAT was an investigator-initiated, multicentre, randomised, double-blind, placebo (PBO)-controlled trial. Patients with inflammatory and EOA, according to the ACR criteria, with radiographically erosive disease were randomised 1:1 to HCQ 200-400 mg/day or PBO for 52 weeks (W52). Both groups received stable standard therapy. The primary endpoint was Australian Canadian Hand Osteoarthritis Index (AUSCAN) for pain and hand disability at W52. RESULTS: 75 patients were randomised to HCQ and 78 to PBO. At W52, mean AUSCAN pain was 26.7 in HCQ and 26.5 in PBO patients (p=0.92). Hand disability measured by AUSCAN function (mean) was 48.1 in HCQ and 51.3 in PBO patients (p=0.36). Changes in radiographic scores did not differ significantly (p>0.05) between treatment groups. There were 7 serious adverse events in the HCQ and 15 in the PBO group. CONCLUSIONS: OA-TREAT is the first large randomised PBO controlled trial focusing on EOA. HCQ was no more effective than PBO for changes in pain, function and radiographic scores in the 52-week period. Overall safety findings were consistent with the known profile of HCQ.

Current Treatment Options for Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease and a leading cause for impaired function and disability with significant treatment costs and socio-economic burden. Despite recent achievements in the knowledge on disease pathogenesis, the treatment is still a challenge and contrary to the inflammatory joint diseases, no disease-modifying drugs are currently available for OA. Different response in different localizations of the disease further complicates the therapeutic choice. The standard pharmacological treatment includes agents for control of pain and inflammation (non-steroidal anti-inflammatory drugs, analgesics including opioids, intraarticular corticosteroids) and the group of the symptomatic slow acting drugs for OA such as glucosamine sulfate, chondroitin sulfate, diacerein, unsaponifiables extract of soybean and avocado administered orally and intrarticular hyaluronic acid. In addition, a number of studies investigate the efficacy of classic disease-modifying drugs used in inflammatory arthritides and antiresoptive agents as potential future therapies that could prevent structural progression of the disease. In a number of small studies, therapeutic efficacy of hydroxychloroquine (HCT) in OA has been suggested, but the results are contradictory. The first results from a multicenter, randomized, double-blind, placebo-controlled trial focused on symptomatic hand OA were recently reported (British HERO study). It has been concluded that HCQ was not superior than placebo as analgesic treatment or for reduction of the radiographic progression in hand OA. Placebo-controlled trial evaluating the efficacy of HCT in inflammatory and erosive hand OA is under way (OA TREAT study). Another field of recent research is the efficacy of TNF-alpha blockers based on the knowledge of their high efficacy in the inflammatory joint diseases and the significant role of TNF-alpha in the pathogenesis of OA. However, current evidence from the available studies does not support the use of TNF-alpha blockers in OA. The benefit of TNF-alpha blockers in specific sub-groups of patients with higher level of inflammation, objective criteria for the expected responders as well as cost-effectiveness of such treatment is a matter of further research and discussion. New biologic agents that target the nerve growth factor-ß are other currently investigated drugs as a potential symptomatic therapeutic option in OA. Significant research has been also focused on revealing potential symptomatic or eventually disease-modifying efficacy of drugs that target bone metabolism due to contemporary notion for the crucial role of the subchondral bone in OA pathology and the positive association between the increased subchondral bone turnover and the progressive cartilage loss. A significant delay of joint width narrowing vs. placebo has been observed in patients with symptomatic knee OA after treatment with strontium renelate. The intraarticular administration of platelet-rich plasma is evaluated as potential future therapy and has been tried in knee and hip OA with beneficial effect. Based on the current knowledge about the OA pathogenesis and the undergoing studies, new therapies for OA are awaited both as a safe symptomatic treatment - alternative to the conventional treatment options and as a disease-modifying therapy that would revolutionize the contemporary approach to OA.

Current immunotherapy in rheumatoid arthritis.

Rheumatoid arthritis is a common autoimmune disease primarily manifesting as chronic synovitis, subsequently leading to a change in joint integrity. Progressive disability and systemic complications are strongly associated with a decreased quality of life. To maintain function and health in patients with rheumatoid arthritis, early, aggressive and guided immunosuppressive therapy is required to induce clinical remission. Antirheumatic drugs are capable of controlling synovial inflammation and are therefore named 'disease-modifying antirheumatic drugs' (DMARDs). This article aims to bridge the beginning of DMARD therapy with agents such as methotrexate, leflunomide, sulfasalazine, injectable gold and (hydroxy)chloroquine with biological therapies, and with the new era of kinase inhibitors. Mechanisms of action, as well as advantages and disadvantages of DMARDs, are discussed with respect to the current literature and current recommendations.

Comparison of qualitative and quantitative analysis of capillaroscopic findings in patients with rheumatic diseases.

No guidelines for the application of qualitative and quantitative analysis of the capillaroscopic examination in the rheumatologic practice exist. The aims of the study were to compare qualitative and quantitative analysis of key capillaroscopic parameters in patients with common rheumatic diseases and to assess the reproducibility of the qualitative evaluation of the capillaroscopic parameters, performed by two different investigators. Two hundred capillaroscopic images from 93 patients with different rheumatic diseases were analysed quantitatively and qualitatively by two different investigators. The distribution of the images according to the diagnosis and the microvascular abnormalities was as follows-group 1: 73 images from systemic sclerosis patients ("scleroderma" type pattern), group 2: 10 images from dermatomyositis ("scleroderma-like" pattern), group 3: 25 images from undifferentiated connective tissue disease and different forms of overlap (24 "scleroderma-like"), group 4: 26 images from systemic lupus erythematosus patients, group 5: 46 images from rheumatoid arthritis and group 6: 20 images from primary Raynaud's phenomenon patients. All the images were mixed and blindly presented to both investigators. For comparison of the quantitative and qualitative method, investigator 1 assessed presence of dilated, giant capillaries and avascular areas quantitatively by the available software programme and his estimates were compared with the results of investigator 2, who assessed the parameters qualitatively. In addition, the capillaroscopic images were evaluated qualitatively by the investigator 1 and 2 for presence of dilated, giant capillaries, avascular areas and haemorrhages. The comparison of the quantitative and qualitative assessment of the two investigators demonstrated statistically significant difference between the two methods for the detection of dilated and giant capillaries (P < 0.05) but no significant difference regarding the detection of avascular areas (P > 0.05). As we further analysed the results for the capillaroscopic images, demonstrating a "scleroderma" and a "scleroderma-like" pattern (170/200), analogous results were found for the evaluated parameters. Among the 20 capillaroscopic images from patients with primary RP, the estimates for the absence of giant capillaries and avascular areas were equal in 100% (P > 0.05). Comparing the qualitative assessment of the two investigators, a statistically significant difference between estimates of the two investigators was found for the presence of dilated capillaries (P < 0.05), while for giant capillaries, avascular areas and haemorrhages the difference was not statistically significant (P > 0.05). The results of the study have shown that qualitative assessment of capillaroscopic parameters in patients with rheumatic diseases is an adequate method for the everyday rheumatologic practice, especially in cases with primary RP for exclusion presence of microangiopathy. No significant difference between qualitative and quantitative methods of assessment was found for the detection of avascular areas. However, the quantitative analysis is more precise especially for the detection of capillary dilation. A good reproducibility of the qualitative evaluation, performed by two different investigators was also found.

Capillaroscopic pattern at the toes of systemic sclerosis patients: does it "tell" more than those of fingers?

PURPOSE: The aim of the study was to compare nail fold capillaroscopic findings of the fingers with those of the toes in patients with systemic sclerosis (SSc). METHODS: Thirty-six patients with SSc were included in the study: 30 patients had limited SSc, 5 patients had diffuse SSc, and 1 patient had an overlap syndrome. Of these 36 patients, 30 were women and 6 were men (mean [SD] age, 56 [14] years). The severity of the Raynaud phenomenon (RP), the presence of digital ulcers, and skin scores at the fingers and feet were assessed. Nail fold capillaroscopy was performed with a videocapillaroscope (Videocap 3.0; DS Medica). RESULTS: All 36 patients (100%) reported about symptoms of RP in the hands and 34 (94.4%) reported episodes of RP in the feet; the difference is not significant (P > 0.05). In most patients with RP symptoms of both hands and feet, the symptoms were more severe at the hands (82%, 28/34). Digital ulcers of the fingers were found in 36% (13/36) of the case and those of the toes were found in 8.3% (3/36) of the cases. Nail fold capillaroscopy of the hands showed the classic "scleroderma"-type capillaroscopic pattern in 97.2% (35/36) of the patients. In the toes, a scleroderma-type capillaroscopic pattern was found only in 66.7% (24/36) of patients (P < 0.05). With respect to distinct differences, in the toes, the dilated capillaries were found in 72.2% (26/36) of the cases, giant capillaries in 30.6% (11/36) of the cases, hemorrhages in 8.3% (3/36) of the cases, avascular areas in 41.7% (15/36) of the cases, and neoangiogenesis in 22.1% (8/36) of the cases. This difference in frequency of the findings regarding the toes and the fingers of patients with SSc was statistically significant for all parameters. CONCLUSIONS: Capillaroscopy of the toes of SSc also shows patterns characteristic of SSc. However, these patterns differ from the respective patterns of the fingers, which is probably related to less-severe RP and lower skin score at the feet.