Outcome of refractory to conventional and/or biologic treatment adult Still's disease following canakinumab treatment: Countrywide data in 50 patients.

OBJECTIVE: To assess the efficacy and safety of the IL-1b inhibitor canakinumab in all adults with refractory Still's disease identified from the National Organization For Medicines for off-label drug use. METHODS: In a retrospective longitudinal multicenter cohort of 50 patients (median age 39 years) with active Still's disease despite treatment with corticosteroids (n = 11), conventional and synthetic (n = 34) and/or biologic disease modifying anti-rheumatic drugs (n = 30), we assessed the efficacy of canakinumab 150-300 mg administered every 4 (n = 47) or 8 weeks (n = 3) as combination therapy or monotherapy (n = 7) during a median follow-up of 27 (3-84) months. RESULTS: Α complete response was initially observed in 78% of patients within 3 months (median), irrespective of age at disease onset. A partial response was evident in 20%. One patient had resistant disease. Treatment de-escalation was attempted in 15 of 39 complete responders and a complete drug discontinuation in 21 patients for 8 months (median). Eleven patients (22%) relapsed during treatment, one during de-escalation process, and 11 after treatment discontinuation. Overall, 9 of 11 relapses were successfully treated with canakinumab treatment intensification or re-introduction. At last visit, 18% of patients were off treatment due to remission and 26% due to disease activity. Canakinumab had a significant corticosteroid sparing effect allowing weaning in 21 of 41 cases. Infections (20%, severe 4%) and leucopenia (6%) led to treatment cessation in one patient. CONCLUSION: High rates of sustained remission were observed in this, largest so far, real-life cohort of adult patients with refractory Still's disease treated with canakinumab.

Subgroups of primary Sjögren's syndrome. Sjögren's syndrome in male and paediatric Greek patients.

OBJECTIVES: To describe the clinical and serological findings in male and paediatric Sjögren's syndrome (SS) patients. PATIENTS AND METHODS: Using the European criteria for the diagnosis of SS 12 male and 13 paediatric patients were identified and compared with those of 30 consecutive unselected adult female SS patients. RESULTS: The mean (SD) age of paediatric patients was 9.4 (2.2) years, ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial clinical manifestation in the majority of the children with a statistical significance compared with male (p < 0.01) and with female patients (p < 0.0001). Sicca manifestations were the most common clinical symptoms in male and female patients at disease onset. The systemic manifestations were similar among the three groups except that men showed lower frequency of arthritis (p < 0.05) and Raynaud's phenomenon (p < 0.05) compared with women. No differences were found among the immunological profile of children and female patients, while male patients had a lower frequency of antinuclear antibodies (p < 0.025) and antibodies to Ro(SSA) nuclear antigens (p < 0.025) compared with women. CONCLUSION: Primary SS is rare in children and men in Greece. Recurrent parotid gland enlargement is the most common clinical finding at disease onset in children. Male patients seem to have less systemic manifestations and lower frequency of autoantibodies.

Influence of methotrexate on radiographic progression in rheumatoid arthritis: a sixty-month prospective study.

OBJECTIVE: To evaluate if methotrexate (MTX) can slow disease progression, as determined radiographically, in comparison to other disease modifying drugs in rheumatoid arthritis (RA) patients. MATERIALS AND METHODS: Pairs of hand and wrist radiographs from 30 patients treated with MTX and 30 treated with D-penicillamine (DP) were evaluated blindly and separately by two radiologists (A and B) using reference radiographs for scoring. A scale scoring similar to Larsen's standard radiographs with minor modifications was used. The radiographs studied were obtained at the beginning and 5 years after therapy in both groups. RESULTS: A significantly greater worsening was found in the DP-treated patients (p = 0.025), as compared to MTX patients. Methotrexate showed a slower rate of disease progression than DP. Furthermore, in the MTX group 15 patients remained radiographically stable, 9 worsened and 6 were healed. In contrast, in the DP group 22 patients remained radiographically stable, 8 worsened and none improved. CONCLUSIONS: The rate of radiographic progression in RA patients was lower in MTX-treated patients compared to those treated with DP. Six patients showed radiological improvement after MTX treatment. Therefore, it seems that MTX could be considered a disease modifying drug.

Inner ear involvement in rheumatoid arthritis: a prospective clinical study.

Sensorineural hearing loss in rheumatoid arthritis (RA) has been reported to be the result of the extra-articular manifestation of the disease (rheumatoid nodular vasculitis) or due to drug ototoxicity. In an attempt to investigate the presence of sensorineural hearing loss and the possible causes for it we investigated prospectively 45 RA patients (42 female; three male) with a mean age of 52.5 +/- 10.7 years and a mean disease duration of 8.5 +/- 7.3 years. All patients underwent a complete physical examination and audiological evaluation which included pure tone audiometry and impedance audiometry (tympanogram, static compliance, acoustic reflex, reflex decay, acoustic reflex latency test. We found a sensorineural hearing loss > 20 dB HL in 44.4 per cent (40/90) ears. In all cases the site of hearing loss was the cochlea and in most of them it was bilateral and symmetric (16 patients out of 45 had bilateral sensorineural hearing loss i.e. 35.5 per cent. There was no correlation between sensorineural hearing loss and age, sex, disease duration, articular and extra-articular manifestations and the presence of autoantibodies in our patients. In addition, no correlation was found between sensorineural hearing loss and drug therapy for one at least of the following drugs: NSAIDs, D-penicillamine, plaquenil and methotrexate. We noticed a prologation of acoustic reflex latency in five patients (10 per cent) which was found to be correlated with the temporomandibular joint involvement and the presence of rheumatoid factor (RF). We conclude that inner ear involvement in RA is expressed by: (1) mild symmetric, bilateral sensorineural hearing loss of cochlear type in 35.5 per cent of patients; (2) normal acoustic reflex thresholds; (3) nondecay; and (4) prologation of acoustic reflex latency which appeared in a small number of patients (10 per cent).

Antiphospholipid syndrome: clinical and therapeutic aspects.

The purpose of the present study was to evaluate patients with the antiphospholipid syndrome with particular attention to their initial clinical features, final diagnoses and the course of thrombotic events in association with therapy. The methodology applied was the following: retrospective analysis of 30 patient files (20 female, 10 male) with antiphospholipid syndrome (APS). Four types of therapy were evaluated for their efficacy to prevent thrombotic recurrences, aspirin 100 mg daily plus low-dose prednisone 10-15 mg daily, warfarin (with international normalized ratio 2 to 2.6), immunotherapy alone and no therapy. None of the patients was followed-up during pregnancy. The probability of thrombosis-free survival was estimated according to Kaplan-Meier method, while the statistical significance was tested by the log rank test. There were 21 patients with primary APS and 9 with secondary, 8 of whom had SLE and one patient who had primary Sjögren's syndrome. The age at onset and the disease duration did not differ between men and women, while patients with secondary APS had a longer disease duration than patients with primary APS, a finding indicating that SLE patients develop, for unknown reasons, APS a long time after the initiation of their disease. Twenty patients experienced recurrent thrombotic events (a total of 46 recurrences) of which 43 (93%) were identical to the first event. Thus, in the majority of the cases arterial were followed by arterial and venous by venous thrombotic events: a finding suggesting a tissue-related factor for initiation of thromboses.(ABSTRACT TRUNCATED AT 250 WORDS)

D-penicillamine induced myasthenia gravis: clinical, serological and genetic findings.

Eight cases of D-penicillamine (DP) induced myasthenia gravis (MG) are presented. Seven patients were being treated for rheumatoid arthritis (RA) and one for scleroderma. The mean duration of DP treatment until the myasthenic symptoms developed ranged from 2-8 months. The DP dose reached 500 mg daily. It was found that the clinical and immunological findings were almost similar to those of idiopathic MG, but were less severe. All patients had increased titers of acetylcholine receptor antibodies in their sera. Discontinuation of D-penicillamine resulted in the complete resolution of myasthenic symptoms after 2-6 months. One patient required ventilation, immunosuppressive therapy and plasma exchange. No association was found between DP related MG and the various autoantibodies tested. Immunogenetic analysis showed that three patients had HLA-DR1, two HLA-DR3, one HLA-DR4 and one HLA-DR5. In conclusion, the clinical presentation of DP-induced MG seems similar to idiopathic MG. DP-related MG is relatively benign, although it sometimes can cause life-threatening muscle weakness requiring aggressive therapy. The relatively small number of patients included in this study, however, does not permit any firm conclusions regarding the HLA associations of DP-related MG.