Management of Peripheral Arthritis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. METHODS: A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings. RESULTS: The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain. CONCLUSION: Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations.

Association of polymorphisms in promoter region of TNF-α -238 and -308 with clinical outcomes in patients with immune-mediated inflammatory diseases on anti-TNF therapy.

The hypothesis of the study was that polymorphisms in promoter regions -238 and -308 of TNF-α could be associated with different clinical outcomes in inflammatory bowel diseases (IBD) and immune-mediated rheumatic diseases (IMRD). The aim was to examine the possible association of both polymorphisms with concentration of C-reactive protein (CRP) and fecal calprotectin (fCAL), onset of the remission and development of the ADA in patients on therapy with anti-TNF inhibitors. The prospective study was done in patients with IBD and IMRD on infliximab (IFX) or adalimumab (ADM). Patients were genotyped for TNF-α -238 and -308 polymorphisms. The concentration of CRP, fCAL, IFX or ADM and antibodies to drugs were measured according to manufacturer's instructions and followed-up for 6 or 12 months. Out of all patients (N = 112), number of patients in remission did not differ according to genotypes (for IBD patients P = 0.509 vs 0.223; for IMRD patients P = 0.541 vs 0.132 for TNF-α -238 and -308, respectively). Initial CRP concentration was higher in IBD patients with TNF-α -308 GG than GA/AA genotypes in patients who failed to achieve remission [11.8 (4.4-39.6) vs 3.1 (1.5-6.5), P = 0.033]. In IBD patients with remission, fCAL concentration after at least 6 months of therapy was higher in TNF-α-308 GG than in GA genotype [52 (25-552) vs 20 (20-20) µg/g, P = 0.041]. Our results showed the association of TNF-α -308 GG genotype with a higher concentration of CRP and fecal calprotectin in patients with inflammatory bowel diseases on IFX or ADM therapy. Clinical remission and development of antibodies to anti-TNF drugs were not associated with TNF-α -238 and -308 polymorphisms.

Post-COVID-19 exacerbation of fibrodysplasia ossificans progressiva with multiple flare-ups and extensive heterotopic ossification in a 45-year-old female patient.

Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Since January 2021, the patient felt unwell, with occasional abdominal pain which progressively intensified. In March 2021 she presented with new onset of HO, complaining of pain, swelling and thickening sensation in the lower abdomen and left part of the neck. Computerized tomography (CT) and cytokine analysis were performed. CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progression. Radiotherapy, which has proven to be an efficient tool to control HO in this patient, was not able to halt HO formation after COVID-19 infection. Cytokine analysis of a plasma sample obtained during a flare-up after COVID-19 infection showed a significantly elevated pro-inflammatory cytokines compared to a flare-up panel prior to infection. Of the 23 analyzed levels of cytokines, a staggering number of 21 were above normal levels. This case is the first confirmation of uncontrolled post-COVID-19 effects in a FOP patient, which manifested with flare-ups followed by progressive HO, possibly caused by a thus far, never described form of post-COVID syndrome.

Lower concentration of vitamin D is associated with lower DAS28 and VAS-pain scores in patients with inflammatory rheumatic diseases treated with infliximab: a pilot study.

Vitamin D is beneficial in patients with immune-mediated rheumatic diseases as it has been shown that it lowers the incidence risk and the level of inflammation. To examine the association between clinical outcomes and initial 25-hydroxyvitamin D [25(OH)D] concentrations in patients with the immune-mediated rheumatic diseases treated with infliximab for 9 months. This study was performed in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with infliximab for at least 38 weeks. Disease activity was assessed using Disease Activity Score (DAS28) for RA and PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS, while the global assessment was performed using the Visual Analogue Scale (VAS). Patients were divided into 2 groups according to 25(OH)D concentration which was classified as deficient or non-deficient (below and above 50 nmol/L, respectively). Concentrations of infliximab (IFX) and C-reactive protein (CRP) were measured according to the manufacturer's instructions.This study was performed in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with infliximab for at least 38 weeks. Disease activity was assessed using Disease Activity Score (DAS28) for RA and PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS, while the global assessment was performed using the Visual Analogue Scale (VAS). Patients were divided into 2 groups according to 25(OH)D concentration which was classified as deficient or non-deficient (below and above 50 nmol/L, respectively). Concentrations of infliximab (IFX) and C-reactive protein (CRP) were measured according to the manufacturer's instructions. The study included 23 patients (14 with RA, 6 with AS and 3 with PsA), median age 54 years, 15 females. Vitamin D deficient and non-deficient groups had median initial concentrations of 38 and 61 nmol/L, respectively. DAS28 and pain on VAS calculated at the 2nd and 38th week showed a statistically significant decrease only in RA and PsA patients with vitamin D deficiency (P = 0.02 and 0.06, respectively). Lower initial concentration of 25(OH)D in patients treated with infliximab was associated with better improvement of clinical measures (DAS28 and VAS) of disease after 9 months of therapy.

Elevated plasma RANTES in fibrodysplasia ossificans progressiva - A novel therapeutic target?

Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary disease caused by a mutation in the intracellular domain of the activin A receptor type I and is characterized by episodes (flare-ups) of progressive heterotopic endochondral ossification (HO) in the soft tissues. The mutation alone is not sufficient for the occurrence of HO since flare-ups are triggered by inflammation and activation of the innate immune system. A number of cellular and humoral mediators have been implicated in animal and in vitro models. Observations in humans support the inflammatory nature of the condition, but data on the involved mediators are variable. We hypothesize that for induction of flare-ups in patients with FOP increase in at least one of the pro-inflammatory cytokines is both essential and sufficient to trigger the entire process of the inflammatory cells influx resulting in the novel ectopic bone formation and we suggest that C-C motif ligand 5 (CCL5), a pro-inflammatory chemokine also known as Regulated on activation, normal T-cell expressed and secreted (RANTES), might be the key candidate. CCL5 is a chemoattractant for all cellular types implicated in HO and is produced by the cells of the tissue microenvironment at the sites of HO as well as by the pro-inflammatory cellular mediators. CCL5 induces ossification in cultured human pluripotent mesenchymal cells (hMSCs) and in the primary culture of monocytes from FOP patients (but not from their healthy relatives), stimulation with lipopolysaccharide induces CCL5 expression. Finally, in a pilot study we used a panel of 23 cytokines and chemokines to screen the plasma samples of three subjects: a female patient with FOP during a flare-up; a female patient with hyperostosis corticalis generalisata (van Buchem disease), another rare disease characterized by excessive bone formation at the sites where it regularly occurs that does not include inflammatory events; and a healthy woman without bone disorders. There appeared a rather clear-cut signal of a 2-fold higher level of CCL5 in the FOP patient vs. the healthy subject and the van Buchem patient. Evaluation of the hypothesis would require an international prospective study, with main motivation being the lack of a conclusive treatment as the major unmet need in FOP. A treatment targeting CCL5 receptor already exists and is used in HIV-infected patients.

Measurement properties of the ASAS Health Index: results of a global study in patients with axial and peripheral spondyloarthritis.

OBJECTIVES: To evaluate construct validity, interpretability, reliability and responsiveness as well as determination of cut-off points for good and poor health within the original English version and the 18 translations of the disease-specific Assessment of Spondyloarthritis international Society Health Index (ASAS HI) in 23 countries worldwide in patients with spondyloarthritis (SpA). METHODS: A representative sample of patients with SpA fulfilling the ASAS classification criteria for axial (axSpA) or peripheral SpA was used. The construct validity of the ASAS HI was tested using Spearman correlation with several standard health outcomes for axSpA. Test-retest reliability was assessed by intraclass correlation coefficients (ICCs) in patients with stable disease (interval 4-7 days). In patients who required an escalation of therapy because of high disease activity, responsiveness was tested after 2-24weeks using standardised response mean (SRM). RESULTS: Among the 1548 patients, 64.9% were men, with a mean (SD) age 42.0 (13.4) years. Construct validity ranged from low (age: 0.10) to high (Bath AnkylosingSpondylitisFunctioning Index: 0.71). Internal consistency was high (Cronbach's α of 0.93). The reliability among 578 patients was good (ICC=0.87 (95% CI 0.84 to 0.89)). Responsiveness among 246 patients was moderate-large (SRM=-0.44 for non-steroidal anti-inflammatory drugs, -0.69 for conventional synthetic disease-modifying antirheumatic drug and -0.85 for tumour necrosis factor inhibitor). The smallest detectable change was 3.0. Values ≤5.0 have balanced specificity to distinguish good health as opposed to moderate health, and values ≥12.0 are specific to represent poor health as opposed to moderate health. CONCLUSIONS: The ASAS HI proved to be valid, reliable and responsive. It can be used to evaluate the impact of SpA and its treatment on functioning and health. Furthermore, comparison of disease impact between populations is possible.

Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there are no universally effective therapies. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in animal models. One well-characterized cytokine-inhibiting mechanism, termed the "inflammatory reflex," is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthritis severity in mice and rats. It previously was unknown whether directly stimulating the inflammatory reflex in humans inhibits TNF production. Here we show that an implantable vagus nerve-stimulating device in epilepsy patients inhibits peripheral blood production of TNF, IL-1ß, and IL-6. Vagus nerve stimulation (up to four times daily) in RA patients significantly inhibited TNF production for up to 84 d. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly. Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans. These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases.

[Controlled-release oxycodone in the treatment of chronic musculoskeletal pain: A preliminary experience of rheumatology center].

In the etiology of non-malignant pain, a significant proportion is constituted by patients with pain originating in the musculoskeletal system. The use of strong opioids in the treatment of non-malignant pain is still controversial. Therefore, the aim of this study was to establish the efficacy and safety of oxycodone with a controlled release of the active substance (CR) in the treatment of patients with chronic, not well-controlled musculoskeletal pain. Here we present our preliminary results. In this prospective, open, single-center study conducted at a rheumatology center we enrolled consecutive patients with musculoskeletal pain due to a variety of musculoskeletal diseases (osteoarthritis, pain in the lower back, spondyloarthritis), who suffered from moderate to severe pain despite previous analgesic therapy (with NSAIDs, weak opioids, or a fixed combination of paracetamol and weak opioids). Patients were switched to therapy with oxycodone CR and followed for 14 days. The starting dose of oxycodone CR was 10 mg, and later the dose was adapted as necessary. The primary endpoint was to assess the effectiveness of oxycodone CR on pain intensity, and the secondary goal was to assess the efficiency on the general health of the patient (both on a horizontal visual analogue scale, VAS 0 = best, 10 = worst). Fifteen patients (12 women, 3 men), with a mean age of 61 ± 12 years and a diagnosis of osteoarthritis, pain in the lower back, or inflammatory arthritis, were included in the study. The duration of pain was 41 ± 12 months. The average intensity of pain before oxycodone CR treatment was 7.87 ± 2.28 (range 7-10), and at the end of the study it was 5.92 ± 2.43 (range 4-9) (p=0.069). General health was rated 7.27 ± 2.14 (range 3-10) before the start and 6.00 ± 1.53 (range 3-9) at the end of the study (p=0.028). In one patient the treatment was discontinued due to dizziness and nausea, and one patient voluntarily left the study because of fear and the subjective impression of no adequate pain control after 2 days of treatment. The oxycodone side-effect profile was as expected. Results of our preliminary study show that in patients with chronic non-malignant pain which is not well controlled by simple analgesics, NSAIDs, and weak opioids, treatment with oxycodone CR contributed to a significant reduction in the level of pain and improved the general health of the subjects.

[RETROSPECTIVE DATA ANALYSIS OF THE PATIENTS WITH INFLAMMATORY JOINT DISEASES TREATED WITH GOLIMUMAB IN CROATIA]. / RETROSPEKTIVNA ANALIZA PODATAKA BOLESNIKA OBOLJELIH OD UPALNIH REUMATSKIH BOLESTI U HRVATSKOJ LIJECENIH GOLIMUMABOM.

Golimumab is a human monoclonal antibody which inhibits tumor necrosis factor-alpha (TNF-α) and is approved for the treatment of inflammatory arthritides (rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis) when the conventional non-pharmacological and pharmacological therapies fail to cause remission or low disease activity. In this retrospective study there were included patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis who were treated in Croatia with golimumab, from June 2011 to June 2013. included and these retrospective data are compared with similar data from clinical trials and other available databases. Standard variables of disease activity and functional ability were observed. Results demonstrated significant efficacy of golimumab regarding lowring the disease activity and imrpving functional ability in pateints with these inflammatory rherumatic disease. In conclusion, in this retrospective study during two years treatment golimumab showed efficacy in decreasing disease activity and imrpove functional ability in patiemts with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

Vitamin D serum level, disease activity and functional ability in different rheumatic patients.

BACKGROUND: The aim of the study was to determine the serum vitamin D levels in patients with psoriatic arthritis (PsA) and compare it with patients with rheumatoid arthritis (RA) and with osteoarthritis (OA), as well as to explore the relationship of the vitamin D level with indices of disease activity and functional ability in a real-life setting in a South-European country. METHODS: In a cross-sectional study, 120 adult patients with established diagnosis of PsA, RA and OA were consecutively enrolled. Serum 25-hydroxyvitamin D and intact parathyroid hormone were determined. Parameters of disease activity and functional ability were obtained using standard instruments. RESULTS: Serum vitamin D insufficiency (≤ 75 nmol/L) was found in 74% of patients with PsA, 94% patients with RA and 97% of patients with OA, whereas vitamin D deficiency (≤ 25 nmol/L) was found in 13% of patients with PsA, 39% of patients with RA and in 38% of patients with OA. Compared with RA, patients with PsA had significantly higher serum vitamin D (P = 0.002), and when controlling for age and gender, their serum vitamin D level was significantly associated with disease activity and functional activity. CONCLUSIONS: In the group of rheumatic patients, a high prevalence of serum vitamin D insufficiency/deficiency was found regardless of the type of arthritis. Patients with PsA might have higher levels of vitamin D than patients with RA, and this was associated with disease activity and functional ability. The results of this study indicate that prophylactic supplementation with vitamin D might be recommended for all rheumatic patients.

An unusual manifestation of osteoarticular tuberculosis: case report.

Although osteoarticular tuberculosis is usually presented as monoarthritis of the large, weight-bearing joints (predominantly hip, knee or ankle joint), or in the form of spinal disease, it is rarely seen as oligoarthritis. In this article, we present case history of a female patient with tuberculous oligoarthritis of the right talocruraljoint and left talocalcaneal joint. A 77-year-old female patient was admitted to our department due to the symptoms of painful and swollen right talocrural joint and left talocalcaneal joint accompanied with fever, general weakness and night sweating. Laboratory findings, including erythrocyte sedimentation rate, whole blood count, liver and kidney functional tests showed no significant changes. Plain x-rays and magnetic resonance imaging of the affected joints showed demineralization, significant narrowing of joint space, erosions of articular surfaces, numerous calcifications, and ankylosis of both right talocrural and left talocalcaneal joint. Synovial biopsy confirmed the diagnosis of tuberculous arthritis. Our patient underwent triple tuberculostatic therapy with rifampicin, isoniazid and pyrazinamide, which resulted in the resolution of arthritis.

[The proposal of Croatian Society for Rheumatology for anti-TNF-alpha therapy in adult patients with spondyloarthritides, 2013]. / Prijedlog hrvatskog reumatoloskog drustva HLZ-a za primjenu inhibitora TNF-alpha u odraslih bolesnika sa spondiloartritisima, 2013.

Croatian Society for Rheumatology of Croatian Medical Association updated the proposal for the application of TNF-alpha inhibitors in adult patients with spondyloartritides (SpA) in accordance with the new classification of SpA and european recommendations for the treatment of SpA with biologic agents. In this way a standardized method of diagnosis, targeted treatment, monitoring and evaluating outcomes are proposed.

Differential expression of proteins with heparin affinity in patients with rheumatoid and psoriatic arthritis: a preliminary study.

OBJECTIVES: Using proteomic approach in this study, we sought to identify proteins with heparin affinity associated with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and non-inflammatory arthritis (NIA). METHODS: Plasma samples from adult RA, PsA and NIA patients, 20 of each, were collected. After enrichment of proteins with heparin affinity, SDS-PAGE and in-gel digestion with trypsin were performed. Peptides were concentrated, micro-purified, separated and measured by nano-scale HPLC system coupled to a mass spectrometer. Peak lists were generated from raw spectra and searched against human complete proteome set by MaxQuant software. Statistical analysis of protein relative expression levels was done in IPython interactive Python shell using NumPy and Matplotlib libraries. Individual protein impact on the whole dataset correlation was done by excluding one protein at a time and calculating the correlation coefficient of remaining data points. RESULTS: Three hundred and eighty-four different proteins were identified keeping false discovery rate to 1%, from which 163 were identified in all three conditions. The plasma proteome showed a good correlation between rheumatoid (RA) and psoriatic arthritis (PsA). Out of 10 proteins whose impact on the correlation coefficient fell outside of two standard deviations from the mean, four were up-regulated (complement factor I, complement component C8 beta, glyceraldehyde-3-phosphate dehydrogenase and inter-alpha-trypsin inhibitor heavy chain H1), and two were down-regulated (immunoglobulin heavy chain V-III region BRO, and immunoglobulin J chain), both in PsA and RA by a similar ratio when compared to NIA. The remaining four proteins (Serpin A11, complement factor H-related protein 5, cartilage acidic protein 1 and coagulation factor IX) were down-regulated in PsA and up-regulated in RA when compared to NIA. CONCLUSIONS: We found differently expressed proteins in patients with inflammatory and non-inflammatory rheumatic conditions. Out of 384 proteins with heparin affinity four proteins should be further validated as potential diagnostic biomarkers in patients with RA and PsA.

Complementary and alternative treatment of musculoskeletal pain.

The use of complementary and alternative medicine (CAM) is high and increasing worldwide. Patients usually use CAM in addition to conventional medicine, mainly to treat pain. In a large number of cases, people use CAM for chronic musculoskeletal pain as in osteoarthritis, back pain, neck pain, or fibromyalgia. Herewith, a review is presented of CAM efficacy in treating musculoskeletal pain for which, however, no scientific research has so far provided evidence solid enough. In some rare cases where adequate pain control cannot be achieved, CAM might be considered in rational and individual approach based on the first general rule in medicine "not to harm" and on the utility theory of each intervention, i.e. according to the presumed mechanism of painful stimulus and with close monitoring of the patient's response. Further high quality studies are warranted to elucidate the efficacy and side effects of CAM methods. Therefore, conventional medicine remains the main mode of treatment for patients with musculoskeletal painful conditions.

[Proposal for biologic drugs therapy in rheumatoid arthritis]. / Prijedlog primjene bioloskih lijekova u reumatoidnom artritisu.

Rheumatoid arthritis is a chronic, inflammatory disease with the prevalence about 1%. Rheumatoid arthritis is characterized with synovitis, often evolve erosions of the joints, pain and functional deficit. Etiology is unknown, but the development of such autoimmune disease is due to genetic and environmental factors. Most of the patients with diagnosis of rheumatoid arthritis use nonbiologic disease modifying antirheumatic drugs. Advances in the undersstanding of the disease process have led to the development of biological agents to treat rheumatoid arthritis. With the use of biologic agents we wish to evolve the goal of therapy from that of symptomatiic relief to clinical remission. Biologic drugs have documented, fast and continuous efficacy with generaly well accepted safety profile. On behalf of Croatian Society for Rheumatology we propose recommendations for the biologic therapy in rheumatoid arthritis.

[Guidelines of the Croatian Society for Rheumatology for the treatment of knee and hip osteoarthritis]. / Smjernice Hrvatskoga reumatoloskog drustva. Za lijecenje osteoartritisa kuka i koljena.

Osteoarthritis of the hip and the knee belongs to one of the most disabiliting conditions. Treatment goals for these patients include a reduction in pain, an improvement in joint mobility and to limit functional impairment. To properly manage osteoarthritis, both nonpharmacologic (non-interventional) and pharmacologic modalities may be employed, while minority of patients will require surgery. According to the available evidence for available therapies and experts' opinion here we present guidelines for the treatment of hip and the knee osteoarthritis in Croatia.

Antibodies targeting mutated citrullinated vimentin in patients with psoriatic arthritis.

Antibodies against mutated citrullinated vimentin (anti-MCV) are of a comparable diagnostic value in rheumatoid arthritis (RA) as antibodies targeting citrullinated peptides (anti-CCP). Anti-CCP are present in up to 15% of psoriatic arthritis (PsA) patients, while the prevalence of anti-MCV in PsA patients has been poorly investigated. The aim of the present study was to assess the prevalence and relevance of anti-MCV antibodies in PsA patients. The study included 56 PsA patients. Clinical features, disease activity, and functional ability were noted by an experienced rheumatologist. Serum samples of all patients were analyzed for anti-MCV and anti-CCP antibodies using enzyme-linked immunosorbent assay. Data on 92 patients with RA, 44 patients with other inflammatory rheumatic diseases, and 107 healthy controls from a previous study were used to compare the prevalence of anti-MCV antibodies in PsA patients. Anti-MCV antibodies were positive in only two out of 56 (3.6%) PsA patients, which was significantly lower compared to RA patients (63%). The anti-MCV level was moderately positive and borderline in one patient each. Both patients had asymmetric polyarthritis, dactylitis, moderate to high disease activity, and were anti-CCP and rheumatoid factor (RF) negative. There was no significant difference in anti-MCV levels according to clinical subtypes of PsA and no correlation of anti-MCV levels with anti-CCP, RF, disease activity variables, and functional ability indices. According to study results, anti-MCV antibodies can be detected in a very small proportion of PsA patients with polyarthritic disease and are primarily related to the polyarthritic pattern rather than the specific diagnosis of RA.

[Proposal for anti-TNFalpha therapy in adult patients with rheumatoid arthritis]. / Prijedlog primjene antagonista TNFalpha u reumatoidnom artritisu.

Rheumatoid arthritis is a chronic, inflammatory disease with the prevalence about 1%. Rheumatoid arthritis is caracterized with synovitis, erosive changes of the joints, pain and functional deficit. Etiology is unknown. In the pathogenesis of rheumatoid arthritis the key role have proinflammatory citokines, particularly, tumour necrosis factor (TNFalpha). TNFalpha blockers have documented, fast and continuous efficacy with generally well accepted safety profile. Nowdays, TNFalpha antagonists are established drugs in early and late phase of rheumatoid arthritis. Prescription of TNFalpha antagonists is controlled, according local restrictions, regarding high costs of the therapy. On behalf of Croatian Society for Rheumatology we propose recommendations for the TNFalpha antagonist therapy in rheumatoid arthritis.

[Adalimumab (Humira)--efficacy in rheumatoid arthritis treatment with particular reference to working ability]. / Adalimumab (Humira)--ucinkovitost u reumatoidnom artritisu s posebnim osvrtom na radnu produktivnost.

Tumor-necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine demonstrated to play an important role in the pathogenesis of rheumatoid arthritis (RA). Adalimumab is a recombinant human monoclonal antibody to TNFalpha. In the PREMIER study, when administered in combination with methotrexate (MTX), adalimumab demonstrated that 49% patients with early RA achieved remission. Adalimumab was effective in improving radiographic outcomes, too. At week 28, 52 and 104 of follow-up there was significantly less radiographic progression in combination group (adalimumab/MTX) than in each monotherapy group (adalimumab or MTX), with adalimumab showing better result than MTX. In a large open-label study with active RA, during adalimumab treatment 25% of patients experienced clinical remission and nearly half achieved minimal disease activity. Combining results from different clinical trials adalimumab has demonstrated up to seven years of efficacy among long-standing RA patients when used in combination with MTX. The percentage ofpatients achieving clinical remission continued to increase after two or more years of continuous treatment with combination therapy. In Health economic outcome study performed in parallel with PREMIER study there was a big reduction of days lost in the combination group (adalimumab/MTX) in comparison with MTX at year 1 and a difference maintained to year 2. The combination therapy was much more successful in maintaining quality of work than MTX. PROWD study, which was the first one to actually look at job loss as the primary outcome, showed that the combination of adalimumab and methotrexate has the ability to reduce job loss and work time lost when compared to just MTX. Adalimumab is the newest developed anti-TNFalpha, which not only demonstrated significant and sustained reduction in signs and symptoms and inhibition of radiographic progression, but has also improved functional status, quality of life and work productivity in patients with RA, with acceptable safety profile.