Combination Therapy MTX was witnessed clinically to be effective but certain side effects were reported which were taken into consideration such as bone marrow suppression, lung or liver toxicity, post-treatment fatigue, headaches, dizziness, nausea, the risk of infection etc. Then the concept of combination therapy came into picture due to the effective experience in leukemia and lymphoma. Several combinations were recruited to visualize the best combination.
The most successful came out to be till now is Cyclosporine (Tugwell et al., 1995). It is also known that MTX in combination with ara-C (Arabinofuranosylcytosine, nucleoside analogue, a chemotherapy agent which requires phosphorylation by deoxycytidine kinase (dCK) before getting incorporated into chromosomes) has effective role in curing leukemia and lymphoma such as non-Hodgkin’s lymphoma including Burkitt’s leukemia/lymphoma (Thomas et al., 1999; Lee et al., 2001).
MTX with few anti-TNF agents has been shown to have curative effect on ulcerative colitis (Herfarth et al., 2016) Apart from Cyclosporine, MTX with hydroxychloroquine and MTX with sulfasalazine were also reported to have a better result as compared to monotherapy. Some negative combinations (with low dose) were also conveyed.
(Willkens et al., 1992) Drug InteractionIt is not advisable that Nonsteroidal anti-inflammatory drugs (NSAIDs) should be administered before or parallel with the high doses of MTX, such as used in the treatment of osteosarcoma. Concomitant administration of some NSAIDs with high dose MTX therapy has been reported to enhance and prolong serum MTX levels, resulting in deaths from severe hematologic and gastrointestinal toxicity.
Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate. (Clinical Oncological Society of Australia: Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia 1983; 1:426-428.) If an extreme decrease in blood cell count is watched/followed, then the drug must be immediately discontinued and appropriate different therapy should be carefully thought about/believed.
If extreme leukopenia and fever happen, the patient should be taken special care with germ-killing substance therapy if there are signs of infection. Blood or platelet transfusions though not successful always but may be necessary for patients with extreme (deep inside of the bones) depression. (McEvoy, G.K. (ed.
). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc.
2005 (Plus Supplements)., p. 11)Current Scenario and Future perspectiveImproved understanding of the medicine-based of methotrexate and the use of this knowledge to the individual patient will reduce further the deadliness of this medically helpful.
The effectiveness of therapy will benefit from the expanded knowledge of the drugs Pharmacokinetics in the target cells. The important and practical results of these advances will bear big improvement in the medically helpful index of methotrexate therapy for all patients with anti-folate harmful, and non-harmful, disease. This is still very exciting drug definitely has more surprises in store for us.
Moving around/misleading and tricking of the MTX molecule may provide a better medically helpful profile for RA patients. So, polyglutamation of the drug, a (related to processing and using food) step that appears to play a role both in its medically helpful properties and liver-related side effects, might be a potential starting point. More than that, methods of targeted drug delivery, in order to increase drug (collection over time) at the site of swelling, may increase effectiveness and reduce poisonous quality. Milk protein-coupled and liposomally conjugated MTX, both of which are more strong than MTX in stopping swelling in animal models, are under preclinical (the process of figuring out the worth, amount, or quality of something). It has been recognized that activated synovial macrophages upregulate FR-Î² expression and that MTX can also become active by this pathway. This makes it possible to develop new FR-Î²-clearly stated folate stoppers with a greater level of detail for this patho-physiologically important cell population (Fiehn, 2011) ConclusionNow there are some studies in response to MTX monotherapy. More specifically, current smoking, female (male/female status), long disease length of time and young age may worse response to MTX treatment.
However, the current mainstream view, which will remain for the near future, is that all patients with RA should start with (good) enough doses of MTX. If this treatment is not effective enough in a reasonable time frame or is poorly tolerated, dose changes/recalculations and adding or replacing another DMARD or a (poison, disease, etc.) should be carefully thought about, taking into account the individual patient and disease. The development of newer, more effective and better tolerated drugs that may also complete the convenient dosing and reduce the cost of MTX is eagerly waited for (Saevarsdottir et al., 2011)