Efficacy and tolerability of subcutaneously administered methotrexate including dose escalation in long-term treatment of rheumatoid arthritis in a Japanese population.

OBJECTIVES: The aim of this article is to evaluate the efficacy and safety of subcutaneously administered methotrexate (MTX) for Japanese patients with active rheumatoid arthritis. METHODS: MTX-naïve patients were randomized in a 1:1 ratio to receive a 12-week administration of either 7.5 mg MTX subcutaneously (MJK101, a prefilled syringe for subcutaneous injection) or 8 mg MTX orally in Part 1 of the trial. The primary end point was a 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 12. In the second part, all enrolled patients received MJK101 weekly for 52 weeks with doses starting from 7.5 to 15 mg with 2.5 mg increments with the option of self-administration of MJK101. RESULTS: The efficacy of MJK101 was comparable to oral MTX following 12 weeks of treatment at the starting doses. A numerically higher ACR20 response rate and fewer adverse events in particular gastrointestinal adverse events were observed. During long-term subcutaneous treatment, MJK101 was well tolerated across all tested doses. Patients clinically improved upon dose escalation. CONCLUSIONS: Subcutaneously applied MTX (MJK101) was efficient and well tolerated over a long-term treatment period in the Japanese population with doses up to 15 mg/week. Subcutaneous administration of MTX is a beneficial option for Japanese patients with rheumatoid arthritis.

Subcutaneously administered methotrexate for rheumatoid arthritis, by prefilled syringes versus prefilled pens: patient preference and comparison of the self-injection experience.

PURPOSE: This multicenter, randomized, crossover study compared preference, ease of use, acceptability, satisfaction, and safety of repeated subcutaneous (SC) self-administrations with prefilled pens and prefilled syringes delivering methotrexate (MTX), in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: The study (ClinicalTrials.gov number NCT01793259) enrolled 120 patients requiring initiation or intensification of MTX therapy for RA. Patients were randomized to receive the test drug, a prefilled pen (Metex(®) PEN/Metoject(®) PEN), or the reference drug, a prefilled syringe (Metex(®)/Metoject(®)), at doses of 15, 17.5, or 20 mg MTX SC once a week for 3 weeks. This was followed by receipt of the reference drug (prefilled syringe) or the test drug (prefilled pen) in a crossover design, with each patient serving as his/her own control. Questionnaires regarding patient preference, the Self-Injection Assessment Questionnaire (SIAQ), and diaries regarding local tolerability were used to document outcomes. RESULTS: Overall patient preference for the MTX prefilled pen was 75% (P<0.0001). In a six-item questionnaire, 73% to 76% of the patients preferred the prefilled pen in relation to use, acceptability, and satisfaction, and 67% of the patients confirmed that it did not take much effort to overcome SC self-injection with the pen. The SIAQ showed no clinical differences, in any domain scores, between both devices. Overall patient attitude towards self-injection at baseline was positive, as was patient experience with both devices during the study. As well, 92% of physicians and study nurses indicated that they would recommend the MTX prefilled pen to patients for future MTX treatment. The formulations were generally well tolerated. CONCLUSION: SC self-injection of MTX with a prefilled pen was generally preferred, by patients with RA, over a prefilled syringe with regard to use, acceptability, and satisfaction. This is supported by the strong appreciation of their attending study nurses and physicians, for its convenience.

Pediatric Acute Lymphoblastic Leukemia: Efficacy and safety of recombinant E. coli-asparaginase in infants (less than one year of age) with acute lymphoblastic leukemia.

The pharmacokinetics, pharmacodynamics, efficacy and safety of a new recombinant E. coli-asparaginase preparation were evaluated in infants (<1 year of age) with de novo acute lymphoblastic leukemia. Twelve patients were treated according to the INTERFANT-06 protocol and received up to 10,000 U/m(2) recombinant asparaginase as intravenous infusions on days 15, 18, 22, 25, 29 and 33 of remission induction treatment. The asparaginase dose was individually adjusted by protocol to 67% of the calculated dose for infants <6 months, and to 75% of the calculated dose for infants aged 6-12 months. The trough serum asparaginase activities observed were above 20, 50, and 100 U/L in 86%, 71%, and 51% of measured samples, respectively. Looking only at the data assessed 3 days after asparaginase infusion these percentages were 91%, 84%, and 74%, respectively. Asparagine was completely depleted in serum in all but one patient who was the youngest in the study. No anti-asparaginase antibodies were detected during this treatment phase. Observed adverse reactions are known to be possible and are labeled side effects of asparaginase treatment and chemotherapy. We conclude that the asparaginase dose regimen used in infants is safe and provides complete asparagine depletion for the desired time period in nearly all patients. Measured asparaginase trough serum levels justify the higher doses used in infants compared to in older children and show that 3-day intervals are preferred over 4-day intervals. (This trial was registered at www.clinicaltrialsregister.eu as EudraCT number 2008-006300-27).

Tolerability and patient/physician satisfaction with subcutaneously administered methotrexate provided in two formulations of different drug concentrations in patients with rheumatoid arthritis.

OBJECTIVES: To determine preference, satisfaction, usability and local tolerability by patients, physicians and study nurses of two subcutaneously administered methotrexate (MTX) formulations of different concentrations. METHODS: This was an open-label, comparative, within-patient controlled, multicentre study of 132 patients with rheumatoid arthritis (RA). MTX treatment consisted of 20 mg/week administered as a medium-concentration formulation (MC) (2.0 ml of 10 mg/ml solution in prefilled syringe; separate needle) compared to a novel high-concentration formulation (HC) (0.4 ml of 50 mg/ml in prefilled syringe; pre-attached needle). Each treatment was given for three weeks. Questionnaires and visual analogue scales were used to measure outcomes. RESULTS: At the end of the study, 93% of the patients preferred HC over MC as further treatment. Overall assessment of HC was "good" or "very good" in 90.6% vs 34.4% in MC-treated patients. Physician's and patients global assessment of syringe usability showed highly statistically significant differences (P < 0.0001) in favour of HC. Overall assessment by study nurses' and investigators' was "good" (18.8%) or "very good" (81.2%) for HC and "good" in 31.3% or "very good" in 12.5% for MC, and no preference in 50%. Local tolerability improved slightly also with HC. CONCLUSIONS: The total smaller volume of administered drug and the improved usability of a pre-attached needle in combination with a smaller prefilled syringe resulted in preference of the patients of HC over MC. The slightly improved local tolerability may also have added to this preference. This assessment was confirmed by similar assessments made by healthcare professionals. Eudra-CT number: 2007-003591-19.