Bioequivalencia, biosimilares, biológicos subsecuentes, medicamentos intercambiables o sustituibles, ¿son lo mismo? / Bioequivalence, biosimilars, biological subsequent, interchangeable or replaceable drugs, are the same?

Biologic drugs are medicinal substances derived from living cells and generally they are a mix of clinically active and inactive molecules. The final products are the result of proprietary processes and highly sensitive to the specific manufacturing technology and handling. Stability and reproducibility of the processes are crucial to guarantee the safety and efficacy of the end products. National regulatory agencies need to establish a set of standards and mechanisms to certify the similarity between follow on biologics and the reference ones; they also might authorize substantially different manufacturing processes to obtain a biosimilar drug; nevertheless, the producer must demonstrate they own sophisticated biotechnologic facilities, stable manufacturing processes, quality control mechanisms, appropriate storage and transportation, a pharmacovigilance program, and also an end-product with similar efficacy and safety to the reference one, for at least one of the approved clinical indications. Besides of complex analytical assays needed to attest the molecular identities, immunogenicity and purity of the biosimilar drug —among other aspects— the final evidence supporting the similarity on efficacy and safety must be accrued from appropriate randomized controlled trials. Full interchangeability between a reference drug and a biosimilar is not a regulatory requisite yet; on the other hand, some biosimilars have demonstrated that they can fully comply with a scientifically defined standard of safety and efficacy. It should be assumed that two proprietary closely similar manufacturing processes, produce different end-products, similar but not identical between each other...

Las drogas biológicas son generalmente moléculas medicinales grandes, derivadas de células vivas. Están constituidas por principios clínicamente activos e inactivos. El producto final es el resultado de procesos propietarios complejos, al punto que suele sostenerse que la droga es el proceso; su reproducibilidad y estabilidad en el tiempo son cruciales para asegurar su eficacia y seguridad. Las agencias regulatorias autorizan que el proceso productivo de un biosimilar pueda ser substancialmente diferente del original; sin embargo, quien lo produce debe demostrar que dispone de instalaciones tecnológicamente sofisticadas, procesos productivos estables, adecuados controles de calidad, almacenamiento y transporte, programa de fármaco vigilancia, así como un producto terminado eficaz, seguro, estable en el tiempo y comparable con el producto innovador para al menos una de las indicaciones terapéuticas del original. Las pruebas de eficacia, seguridad y similitud con un producto de referencia deben obtenerse insoslayablemente mediante ensayos clínicos apropiados, sin perjuicio de los ensayos analíticos para tipificar las moléculas contenidas en el medicamento y determinar su pureza e inmunogenicidad, entre otros aspectos. Las pruebas de intercambios absolutos, obtenidas en ensayos clínicos, no se han establecido aún como una exigencia regulatoria. Dos procesos productivos similares, pero algo diferentes, no pueden conducir a productos biológicos molecularmente idénticos; no obstante, el producto terminado puede satisfacer suficientemente los criterios de eficacia y seguridad similar a uno de referencia con el cual se compara...

Necrosis intestinal como presentación de enfermedad de Takayasu / Intestinal necrosis as clinical presentation of Takayasuïs arteritis: report of one case

A 32 years old female was admitted to hospital due to acute abdominal pain, nausea, vomiting and liquid stools. Physical examination was normal except for pain on her left inferior abdominal quadrant without peritoneal irritation signs. An abdominal CAT-scan suggested thrombosis at celiac trunk, although the echo Doppler showed no alterations except for signs of ischemia in the distal branch of the superior mesenteric artery. An exploratory laparotomy was performed disclosing a necrosis of the distal ileum and cecum, diffuse peritonitis and thrombosis of the ileocecoapendiculocolic artery. No vasculitis lesions were found in the arteries of medium size examined. A history of intermittent claudication for the past 3 years as well as acrocyanosis, asymmetry of pulses and blood pressure in the superior extremities was ascertained after the surgery. A MRI angiogram showed multiple stenoses and irregularities at the celiac trunk, hepatic, superior mesenteric and fibular arteries. No abnormalities at the aortic arch and its main branches were documented. A sepsis due to Candida sp complicated her postoperatory period. After recovery, prednisone 1 mg/kg/day was started and the anticoagulation continued. The abdominal pain, intermittent claudication and superior limb acrocyanosis disappeared. This is an unusual case of type IV Takayasu's arteritis with acute abdominal signs as the first manifestation

Características clínicas y respuestas al tratamiento sistémico de la epiescleritis y escleritis primarias y secundarias, refractarias al tratamiento local / Clinical feactures and response to systemic treatment in episcleritis and scleritis resistent to local treatment

Background: Scleritis and episcleritis may extend to adjacent ocular tissues with blinding consequences and may be associated with potentially lethal systemic disorders. Aim: To evaluate the ocular complications and systemic disease associations of the different types of scleritis and episcleritis. Patients and methods: Forty six patients with refractory scleritis and episcleritis were studied and treated during the period 1991 to 1998. Results: Necrotizing type was the most common and severe category in the scleritis group of patients. A decrease in vision occurred in 58.3 percent of patients with scleritis v/s a 23.5 percent of patients with epiescleritis (p<0,05). Uveitis was present in 35.4 percent of patients with scleritis and scleromalacia was present in 33.3 percent (p<0,05). A specific disease association was uncovered in 51 percent of scleritis and in 38 percent of episcleritis patients. Rheumatoid arthritis, primary systemic vasculitic disease and Sjsgren syndrome with vasculitis were the most common associated systemic diseases. Three patients with scleritis had tuberculosis. Conclusions: Scleritis is more severe than episcleritis, and necrotizing scleritis is the most severe type of scleritis. Classification of scleritis and episcleritis provides valuable prognostic information. A meticulous approach for the detection of a specific associated disease must be undertaken. Scleritis associated with vasculitis has a worse ocular prognosis than other non infectious diseases. Cyclophosphamide is the most effective inmunosuppresive treatment to control severe ocular involvement

Valor pronóstico del índice de Sharp en la respuesta clínica y de laboratorio a un pulso intravenoso de metilprednisolona en pacientes con artritis reumatoídea / Prognostic value of Sharp index in the clinical and laboratory response to an iv methylprednisolone pulse in patients with rheumatoid arthritis

Background: No reliable variables to predict clinical or laboratory response to treatment in patients with rheumatoid arthritis were available until recently. Aim: To asses the potential predictive value of the Sharp's modified radiographic joint damage index for the assessment of clinical and laboratory response to a methylprednisolone i.v. pulse. Patients and Methods: Twenty-two patients suffering from rheumatoid arthritis received a single i.v. pulse of 1 g of methylprednisolone. Hand X-rays were taken at baseline and blindly scored by two trained radiologists. Clinical and laboratory variables were assessed at baseline and at weekly intervals up to 30 days plus a 60 days final evaluation. Improvement was defined as a 50 percent amelioration in 4 variables. Results: Assessment of radiographic scores had a high correlation between and within observers (intraclass correlation= 0.998). Sharp score did not reach statistical significance as global predictor for the inflammatory variable response to methylprednisolone. However, when the number of swollen joints was taken into account, patients with a low erosive score (Sharp ² 50) had a more prolonged clinical response, than patients with higher erosive score (Sharp >50) (Fisher test p= 0.023). It is of clinical importance to point out that among patients with high Sharp score there were also responders who reached a high level of improvement. A statistically significant correlation between the basal PCR serum titers and the radiographic score (p< 0.02) was observed. Conclusions: The number of swollen joints and other variables that consider joint structural changes should be considered for the assessment of rheumatoid arthritis patients

Comparación de la eficacia clínica de una inyección intraarticular o intralesional de dos preparados de betametasona en pacientes con artrosis o epicondilitis / Comparative effects of intra articular injections of two betametasone preparations in patients with osteoarthritis or epicondilytis

Background: Local infiltration with corticoids is a simple therapy for rheumatic disorders devoid of systemic adverse reactions. Aim: To compare the efficacy of two betametasone preparations from two different pharmaceutical laboratories in the treatment of patients with osteoarthritis or epicondilytis. Patients and methods: Fourty patients with knee osteoarthritis and 12 patients with epicondilytis were studied. Using a double blind protocol, one of the two betametasone preparations was used for local infiltration of the lesions. The change in a global score of clinical variables including pain and disability was assessed after 30 days of the infiltration. Results: In patients with osteoarthritis, the global score decreased significantly with both preparations, but no differences were observed between preparations (7.3ñ1.8 to 3.9ñ2.3 with preparation A and 7.8ñ1.9 to 3.6ñ2.3 with preparation B). In patients with epicondilytis, pain was also significantly reduced but no differences between preparations was observed (7ñ2.1 to 1.4ñ2.5 for preparation A and 4.6ñ2.8 to 1.2ñ1.6 for preparation B). Conclusions: Local infiltration with both betametasone preparations was equally effective in the treatment of patients with knee osteoarthritis or epicondilytis

Pacientes con artritis reumatoidea: estudio de correlación entre la densidad de receptores de glucocorticoides en sinoviocitos y la respuesta clínica al tratamiento esteroidal / Patients with rheumatoid arthritis: correlation study between glucocorticoid receptors density in synoviocits and clinical response to steroidal treatment

The target cellular response to glucocorticoids is proportional to the concentration or affinity of specific receptors to these substances. To look for a correlation between glucocorticoid receptors concentrations in synovial wall cells and the clinical response to steroidal treatment in patients with rheumatoid arthritis. Twenty eight patients with rheumatoid arthritis were studied. Each subject was subjected to a synovial biopsy in which a dry radioautographic technique for diffusable compounds was used. Patients were treated afterwards with 3 500mg iv pulses of methilprednisolone. A mean of 44.8 percent of synovial cells (range 30.1-62.8 percent) had binding sites for 3H dexamethasone. All patients had a significant clinical improvement after methilprednisolone. Multiple regression analysis did not show a correlation between clinical response and glucocorticoid receptor concentration. The lack of association between glucocorticoid receptor concentration and clinical response could be due to the large steroid dose used, that saturated all available receptors

Tratamiento de la enfermedad ocular inflamatoria con glucocorticoides y pulsos de ciclofosfamida / Treatment of inflammatory ocular disease with glucocorticoids and cyclophosphamide pulses

The effectiveness, toxicity and prognosis factors influencing responses to cyclophosphamide (CP) iv pulses plus oral glucocorticosteroids (GC) in patients with GC-resistant ocular inflammatory diseases (OID) was evaluated in a cohort of 15 consecutive patients suffering from active, non-infectious OID refractory to oral GC. All patients underwent monthly evaluations with clinical, hematological, hepatic, renal and ophthalmologic tests. These included checking visual acuity and both anterior chamber and posterior segment inflammation. The overall effect evaluated by repeated measurements ANOVA demonstrated that after an average of 5 CP pulses 1-10, the group showed significant improvement regarding of visual aciuty and inflammation (p<0,000001). Amelioration was not sustained over time in patients with granulomatous iveitis. Patients with retinal vasculitis experienced rapid and sustained recovery. By the end of the follow-up period, 53 percent of the patients had improved, 20 percent remained stationary and 26 percent suffered visual acuity deterioration as compared with the baseline. No serious side effects were detected during treatment and follow-up. Conclusions: a combination of oral GC and iv CP pulses appears to be an effective way to treat patients suffering from noninfectious, non-granulomatous, GC-resistant OID

Osteoporosis regional transitoria y distrofia simpática refleja: ¿entidades distintas o variantes clínicas de una misma enfermedad? / Transient regional osteoporosis and reflex sympathetic dystrophy: different entities or clinical variants of the same disease?

We report a 50 years old male that evolved with alternating episodes of osteoporosis with pain, edema and erythema of both feet. The patient presented clinical and radiological evidences of both transient regional osteoporosis and reflex sympathetic dystrophy. The clinical evolution was documented with magnetic resonance imaging. The hypothesis that bothe entities could be different expressions of a same syndrome is discussed