Biologics and Biosimilars: Differences and Clinical Implications.

Biologics or biopharmaceuticals are drugs derived from living organisms by recombinant technology. Biologics have made a significant contribution to the management of certain chronic diseases such as cancer, rheumatoid, arthritis, ankylosing spondylitis, psoriasis and other immune mediated disorders. Biologics are produced by genetically modifying cells and, are highly complex and expensive to manufacture. Many of them are now facing patent expiry which has paved the way for the development of biosimilars. Biosimilars are biologic medicine that is similar in terms of quality, safety and efficacy but not the same as a registered innovator biologic. The manufacturing of biosimilars has many complexities, such as consistency of manufacturing process, conformation of manufacturing standards and demonstration of product consistency Also, powered clinical trials have to be executed to demonstrate similarity to the innovator biologic. Registration of biosimilars requires a more stringent evaluation than that is required for conventional generics. Biosimilars have the potential to be the molecules of the future as long as they are developed strictly in accordance with comparative procedures mandated by regulatory authorities such as EMA and USFDA. It is believed that the advent of biosimilars will improve patient access to expensive biologics for chronic illnesses. However, it is important that clinicians distinguish between innovator biologics and biosimilars. Physicians should avoid substituting biosimilars for innovators as well as avoid interchangeability as biosimilars are not generics. In addition, pharmacovigilance will be the need of the hour to track down any safety and efficacy problems arising from the use of biosimilars.

Soft tissue rheumatism.

Soft tissue rheumatism includes disorders of tendons and their sheaths, ligaments, bursae, joint capsules, muscles, fasciae and others. Inflammatory signs or systemic manifestations may be lacking in these disorders. Fibrositis, bursitis, tenosynovitis, myositis are some of the common types of soft tissue rheumatism. The disorders can be classified broadly into two groups ie, diffuse and local. Proper history taking and performing detailed examination are very important in arriving at diagnosis. Management includes pain relief by suitable measures. In fibromyalgia diffuse musculoskeletal pain is observed having at least 11 or 18 tender points involving upper and lower body bilaterally.

Malondialdehyde as a sensitive marker of inflammation in patients with rheumatoid arthritis.

Malondialdehyde (MDA) levels in the serum were estimated by MDA-TBA (Thiobarbituric Acid) spectro colorimetric assay method in 23 rheumatoid arthritis (RA) patients and were compared with those in 18 healthy subjects. It was found that the mean levels of MDA (265.15 +/- 68.8 n moles/100 ml) in patients with RA were found to be significantly elevated when compared to the mean of that of controls (128.76 +/- 37.8 n moles/100 ml). This study reveals that MDA assessment appears to be a sensitive marker of inflammation in this chronic auto immune disorder and would help in understanding the nature of inflammatory damage at a cellular level.

Early beneficial effects of low dose oral methotrexate in rheumatoid arthritis.

The effect of low dose methotrexate pulse therapy was studied in 21 patients with active rheumatoid arthritis. Three doses of oral methotrexate 2.5 mg at 12 hourly intervals weekly was administered to all the patients. Patients were followed up for clinical, radiological and serological evaluation. Significant reduction in the number of painful and swollen joints, decrease in the duration of morning stiffness, fall in the erythrocyte sedimentation rate, and improvement in global assessment were seen in 15 patients (71.4%) by the end of 16 weeks. Five patients (23.8%) complained of minor gastric discomfort. None of the patients discontinued the treatment because of any side effect.

Sharing of antigens among filarial species revealed by antibody dependent cell-mediated reactions.

Antisera raised in albino rats against microfilariae of Litomosoides carinii, Brugia pahangi, Brugia malayi and sera from Bancroftian elephantiasis patients promoted rat neutrophil-mediated adherence and cytotoxicity to the microfilariae. Pre-treatment of the immune sera, with microfilarial antigen at a final concentration of 5 and 25 μg per ml blocked cellular adherence and cytotoxicity to the microfilariae indicating the presence of crossreactive antibodies. The heterologous immune sera were effective in eliminating the circulating Litomosoides carinii microfilariae in Mastomys natalensis.

Brugia malayi: serum dependent cell-mediated reactions to microfilariae.

Sheathed and exsheathed microfilariae of Brugia malayi are killed by normal rat cells in the presence of immune serum in vitro. Immune serum heated at 56 degrees C for 1 hour lost this activity which was largely restored by the addition of fresh normal rat serum. EDTA but not EGTA abolished this activity indicating the operation of complement by alternate pathway. Fresh normal rat serum alone promoted cellular adherence without exerting cytotoxicity to the microfilariae. The activity in the immune serum could be removed with Staphylococcus aureus cells containing Protein A or anti-IgG antiserum. The activity could also be absorbed to and eluted from Protein A--sepharose CL-4B suggesting the involvement of IgG. Neutrophils and macrophages participate in the antibody dependent cell-mediated cytotoxicity phenomenon. Eosinophils while adhering to the microfilariae exert cytotoxicity only to the exsheathed parasites.